Drake TM, Riad AM, Fairfield CJ, et al. ^Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study. Lancet July 17, 2021. Volume 398, ISSUE 10296, P223-237, July 17, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00799-6/fulltext
Hospitalization with COVID-19 is associated with high rates of morbidity in adults. In this large prospective cohort study, almost half of the survivors had one or more complications. Rates were high even in young, previously healthy individuals. Acute complications were associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes.
Yoshikawa Y, Kawachi I. Association of Socioeconomic Characteristics With Disparities in COVID-19 Outcomes in Japan. JAMA Netw Open July 14. 2021;4(7):e2117060. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781935?resultClick=1
Disparities in COVID-19 outcomes are not unique to the US and Europe: in this cross-sectional study of the 47 prefectures in Japan, a higher burden of COVID-19 cases and deaths was observed in prefectures with lower household incomes; a higher proportion of the population receiving public assistance; a higher unemployment rate; higher numbers of retail, transportation and postal, and restaurant industry workers; more household crowding; and higher smoking and obesity rates.
Bennett TD, Moffitt RA, Hajagos JG, et al. Clinical Characterization and Prediction of Clinical Severity of SARS-CoV-2 Infection Among US Adults Using Data From the US National COVID Cohort Collaborative. JAMA Netw Open Jul 13, 2021;4(7):e2116901. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781923?resultClick=1
In this cohort study of 174,568 adults with SARS-CoV-2, 32,472 (18.6%) were hospitalized and 6565 (20.2%) got severely ill, and first-day machine learning models accurately predicted clinical severity. Mortality decreased from 16.4% in March to April 2020 to 8.6% in September to October 2020. In a separate multivariate logistic regression model built for inference, age (odds ratio, 1.03 per year), male sex (OR, 1.60), liver disease (OR, 1.20), dementia (OR, 1.26), African-American (OR, 1.12) and Asian (OR, 1.33) race, and obesity (OR, 1.36) were independently associated with higher clinical severity.
Williamson EJ, McDonald HI, Bhaskaran K, et al. Risks of covid-19 hospital admission and death for people with learning disability: population based cohort study using the OpenSAFELY platform. BMJ July 14, 2021; 374. https://www.bmj.com/content/374/bmj.n1592
This large population-based cohort study from England indicates that people with learning disability have markedly increased risks of hospital admission and death from covid-19, over and above the risks observed for non-covid causes of death. Down’s syndrome and cerebral palsy were associated with increased hazards for both events; Down’s syndrome to a greater extent.
COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature July 8, 2021. https://www.nature.com/articles/s41586-021-03767-x
An individual’s genetics can influence their risk of infection and the severity of disease symptoms. This large international study has identified parts of the human genome that can affect the risk of severe COVID-19. Three genome-wide association meta-analyses comprised of up to 49,562 COVID-19 patients from 46 studies identified a total of 13 genome-wide significant loci associated with SARS-CoV-2 infection (n = 4) or severe manifestations of COVID-19 (n = 9). Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases.
Jassat W, Mudara C, Ozougwu L, et al. Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study. Lancet Global Health July 09, 2021. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00289-8/fulltext
Increased mortality in the second wave could be partly explained by more admissions in older individuals and in the public sector, and by higher volumes of hospital admissions. However, the residual 31% increased mortality could possibly be associated with the new beta variant.
Kadri SS, Sun J, Lawandi A, et al. Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020. Ann Int Med July 6, 2021. https://www.acpjournals.org/doi/10.7326/M21-1213
Nearly 1 in 4 COVID-19 deaths was potentially attributable to hospitals strained by surging caseload. Bolstering preventive measures and supporting surging hospitals will save many lives.
Lee SA, Park R, Yang JH. et al. Increased risk of acute kidney injury in coronavirus disease patients with renin–angiotensin–aldosterone-system blockade use: a systematic review and meta-analysis. Sci Rep Jun 30, 2021, 11, 13588. https://www.nature.com/articles/s41598-021-92323-8
This meta-analysis of published retrospective and prospective cohort studies observed that the exposure to RAAS blockade was associated with a higher risk of incident acute kidney injury in patients with laboratory-confirmed or clinically diagnosed COVID-19. Odds ratio were 2.45 for ACEI use and 2.32 for ARB use. However, a causal relationship cannot be ascribed to the RAAS blockade and practice changing recommendations cannot be made on the basis of these data.
Castro MC, Gurzenda S, Turra CM, et al. Reduction in life expectancy in Brazil after COVID-19. Nat Med June 29, 2021. https://www.nature.com/articles/s41591-021-01437-z
The authors estimate a decline in 2020 life expectancy from birth of 1.3 years, a mortality level not seen since 2014. Life expectancy in the presence of COVID-19 was equivalent to levels observed in Brazil as far back as 20 or more years in some states.
Woolf SH, Masters RK, Aron LY. Effect of the covid-19 pandemic in 2020 on life expectancy across populations in the USA and other high income countries: simulations of provisional mortality data. BMJ June 24, 2021; 373 doi: https://doi.org/10.1136/bmj.n1343
Between 2018 and 2020, life expectancy in the US decreased by 1.87 years (to 76.87 years), 8.5 times the average decrease in peer countries (0.22 years). Losses were more pronounced among the Hispanic and non-Hispanic Black populations. Life expectancy in Black men reached its lowest level since 1998.
Steenblock C, Richter S, Berger I. et al. Viral infiltration of pancreatic islets in patients with COVID-19. Nat Commun June 21, 2021, 12, 3534. https://www.nature.com/articles/s41467-021-23886-3
Using human islets and autopsy tissue from patients that died of COVID-19, this study provides clear proof that beta cells are permissive to infection with SARS-CoV-2. The mechanism of virus entry is not completely clear at this point as ACE2 is only expressed in beta cells in a subset of patients. Therefore, other receptors/factors may be involved in facilitating uptake of SARS-CoV-2 into beta-cells. SARS-CoV-2 may induce a local inflammation and may be associated with necroptotic cell death in islets, but the current study cannot answer in detail the mechanism that may lead to islet impairment and metabolic dysregulation.
Yang AC, Kern F, Losada PM, et al. Dysregulation of brain and choroid plexus cell types in severe COVID-19. Nature Jun 21, 2021. https://www.nature.com/articles/s41586-021-03710-0
By combining sequencing of 65,309 nuclei in both the frontal cortex and choroid plexus along with confirmatory IHC and RT-qPCR, this study reveals several major neuropathological mechanisms in severe COVID-19.
Kentish-Barnes N, Cohen-Solal Z, Morin L, et al. Lived Experiences of Family Members of Patients With Severe COVID-19 Who Died in Intensive Care Units in France. JAMA Netw Open June 21, 2021; 4(6):e2113355. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781115?resultClick=1
This study reports how bereaved family members’ experiences of care, death, and mourning were disrupted during the first wave of the COVID-19 pandemic, both during hospitalization in the ICU and after the patient’s death. The main finding is “what family-centered research has taught us in the last 20 years: the presence of family members in ICUs should remain a priority”.
Xin H, Wong JY, Murphy C, et al. The incubation period distribution of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. Clin Inf Dis June 12, ciab501, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab501/6297425
Mean, median and 95th percentile for incubation period are 6.3 days (range: 1.8 to 11.9 days), 5.4 days (range: 2.0 to 17.9 days) and 13.1 days (range: 3.2 to 17.8 days), respectively.
Aschman T, Schneider J, Greuel S, et al. Association Between SARS-CoV-2 Infection and Immune-Mediated Myopathy in Patients Who Have Died. JAMA Neurol June 11, 2021. https://jamanetwork.com/journals/jamaneurology/fullarticle/2781013?resultClick=1
In this case-control autopsy study, SARS-CoV-2 was associated with an immune-mediated myopathy. Of 43 individuals who died with a diagnosis of COVID-19, 26 (60%) showed signs of muscle inflammation, ranging from mild to severe inflammatory myopathy. Detection of viral load was low or negative in most skeletal and cardiac muscle samples, indicating that myopathy was post-infectious, immune-mediated.
Després JP. Severe COVID-19 outcomes — the role of physical activity. Nature Reviews Endocrinology 10 June 2021. https://www.nature.com/articles/s41574-021-00521-1
It’s not only obesity: according to this nice review, current sedentary behaviors and lack of physical activity are also contributing to morbidity and mortality associated with COVID-19.
Discepolo V, Catzola A, Pierri L, et al. Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic. JAMA Netw Open June 10, 2021;4(6):e2111369. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780866?resultClick=1
This case series of 17 adolescents found that chilblain-like lesions of the toes emerged during the COVID-19 pandemic in otherwise healthy adolescents without signs of SARS-CoV-2 infection or other inflammatory, autoimmune, or thrombophilic phenomena.
Oliveira EA, Colosimo EA, Simões e Silva AC, et al. Clinical characteristics and risk factors for death among hospitalised children and adolescents with COVID-19 in Brazil: an analysis of a nationwide database. Lancet Child Adolesc June 10, 2021. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00134-6/fulltext
In this large study from Brazil, death from COVID-19 was associated with age, Indigenous ethnicity, poor geopolitical region, and pre-existing medical conditions.
Christie A, Henley SJ, Mattocks L, et al. Decreases in COVID-19 Cases, Emergency Department Visits, Hospital Admissions, and Deaths Among Older Adults Following the Introduction of COVID-19 Vaccine — United States, September 6, 2020–May 1, 2021. MMWR Morb Mortal Wkly Rep. ePub: 8 June 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7023e2.htm?s_cid=mm7023e2_w
The ratio for COVID-19 deaths began to decline in mid-December while rate ratios for COVID-19 incidence, ED visits, and hospital admissions began to decline in late December to mid-January. Comparing the 2-week pre-vaccination period with 2 weeks in late April, declines were significantly greater among older adults, who had higher vaccination coverage, than among younger adults, who had lower coverage.
Raut A, Huy NT. Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave? Lancet Resp Med June 03, 2021. https://doi.org/10.1016/S2213-2600(21)00265-4
Often referred to as the so-called black fungus, the incidence of mucormycosis has risen more rapidly during the second wave compared to the first wave of COVID-19 in India, with at least 14,872 cases as of May 28, 2021. Brief summary of the situation.
Patel A, Agarwal R, Rudramurthy SM, et al.; MucoCovi Network. Multicenter epidemiologic study of coronavirus disease–associated mucormycosis, India. Emerg Infect Dis. 2021 Sep [date cited]. https://doi.org/10.3201/eid2709.210934
A retrospective observational study involving 16 healthcare centers across India. Among 287 mucormycosis patients, 187 (65.2%) were associated with COVID-19 (CAM); CAM prevalence was 0.27% among hospitalized COVID-19 patients. Hypoxemia due to COVID-19 and inappropriate use of glucocorticoid drugs were independently associated with development of late CAM. The mortality rate for CAM patients was high (44%) but was comparable to rates for non-CAM (49%) patients.
Havers FP, Whitaker M, Self JL, et al. Hospitalization of Adolescents Aged 12–17 Years with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 1, 2020–April 24, 2021. MMWR Morb Mortal Wkly Rep. ePub: 4 June 2021 https://www.cdc.gov/mmwr/volumes/70/wr/mm7023e1.htm?s_cid=mm7023e1_w
Among 204 adolescents who were likely hospitalized primarily for COVID-19 during January 1–March 31, 2021, 31.4% were admitted to an intensive care unit (ICU), and 4.9% required invasive mechanical ventilation; there were no associated deaths.
Kosmicki JA, Horowitz JE, Banerjee N, et al. Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals. The American Journal of Human Genetics June 03, 2021 https://www.cell.com/ajhg/fulltext/S0002-9297(21)00222-6
No significant associations with rare protein-coding variants and COVID-19 outcomes.
Tardif JC, Bouabdallaoui N, L’Allier PL, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Resp Med May 27, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00222-8/fulltext
In this large RCT enrolling high-risk patients from six countries (Brazil, Canada, Greece, South Africa, Spain, and US) who were not under immediate consideration for hospital admission, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Among 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4.6%) of 2075 patients in the colchicine group and 126 (6.0%) of 2084 patients in the placebo group (odds ratio 0.75, 0.57–0.99; p = 0.042). Diarrhea was reported by 14% of patients in the colchicine group and 7% in the placebo group. But do the authors trust their own data? They conclude that “replication in other studies… is recommended”.
Talbot HK, Martin ET; Gaglaniu M, et al. Coronavirus disease 2019 (COVID-19) Versus Influenza in Hospitalized Adult Patients in the United States: Differences in Demographic and Severity Indicators. Clin Inf Dis May 27, 2021, ciab123. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab123/6288408
Anybody talking about “flu”? Comparing 914 hospitalized COVID-19 patients with 1937 influenza hospitalized patients of similar age groups, this study found greater severity and complications with COVID-19: more ICU admissions (AOR = 15.3), ventilator use (AOR = 15.6), 7 additional days of hospital stay in those discharged alive, and death during hospitalization (AOR = 19.8).
Russell CD, Fairfield CJ, Drake TM, et al. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. Lancet Microbe June 2, 2021. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00090-2/fulltext
In 48,902 patients admitted to UK hospitals with COVID-19, microbiologically confirmed bacterial infections were rare, and more likely to be secondary infections (mainly Gram-negative organisms and S aureus). However, the frequency and nature of antimicrobial use was concerning: 85% received one or more antimicrobials at some point during their admission.
Giannis D, Allen SL, Tsang J, et al. Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry. Blood May 20, 2021. https://ashpublications.org/blood/article/137/20/2838/475684/Postdischarge-thromboembolic-outcomes-and
Among 4906 patients, post-discharge thromboprophylaxis was prescribed in 13.2%. Venous thromboembolism (VTE) rate was 1.55% and arterial thromboembolism (ATE) was at 1.71%. Post-discharge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54). Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥ 4, and ICU stay increased risk.
Singh AK, Singh R, Joshi SR, et al. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes & Metabolic Syndrome: Clinical Research & Review. May 21, 2021. https://www.sciencedirect.com/science/article/pii/S1871402121001570
COVID-19-associated mucormycosis (also called “black fungus”, the association of an aggressive fungal infection with COVID-19) has gained much media attraction during recent days. By May 13, this review found a total of 101 cases of which 82 cases had been reported from India. Diabetes was present in 80% of them, while corticosteroid treatment was given for COVID-19 in 76.3%. The most common organ involved with mucormycosis was the nose and sinuses (89%).
Wu CT Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic β-cells and elicits β-cell impairment. Cell Metabolism May 18, 2021. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00230-8
Emerging clinical reports have noted a significant increase in new onset hyperglycemia and diabetes in patients with COVID-19. This study shows that SARS-CoV-2 can directly induce β cell killing. Whereas ACE2 as well as TMPRSS2 were modestly expressed in β cells, selective expression of other critical SARS-CoV-2 entry factors, NRP1 and TFRC, was observed in β cells, indicating that this enrichment is a potential mechanism underlying SARS-CoV-2 tropism for β cells.
Tang X, Uhl S, Zhang T, et al. SARS-CoV-2 Infection Induces Beta Cell Transdifferentiation. Cell Metabolism May 19, 2021. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00232-1
This study shows what happens after ß cell infection: infected beta cells show a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin, respectively, suggesting cellular trans-differentiation.
Islam N, Shkolnikov VM, Acosta RJ, et al. Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries. BMJ May 19, 2021; 373. https://www.bmj.com/content/373/bmj.n1137
In this international comparative study of excess deaths in relation to the COVID-19 pandemic in 29 high income countries, all countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The highest excess deaths were in the US, Italy, England and Wales, Spain, and Poland. Accounting for difference in age, the excess death rates were much higher in men than women in almost all countries.
Li Y, Tong CH, Bare LA, et al. Assessment of the Association of Vitamin D Level With SARS-CoV-2 Seropositivity Among Working-Age Adults. JAMA Netw Open May 19,2021;4(5):e2111634. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779952?resultClick=1
Have you ever heard about the strong correlation between per capita cheese consumption and the number of people who died by becoming tangled in their bedsheets (r=0.95!)? Between the divorce rate in Maine and the per capita consumption of margarine (r=0.99!)? Then please consult this website: http://www.tylervigen.com/spurious-correlations. Vitamin D and COVID-19 seem to be another nice example. In this large study on 18,148 employees and spouses, SARS-CoV-2–seropositive individuals did have lower vitamin D levels than seronegative individuals. However, low vitamin D levels were not independently associated with the risk of seropositivity. Vitamin D deficiency and insufficiency were more common in individuals who had a BMI equal to or greater than 30. And in people who did not have a college degree, or who were younger. Who were current smokers, hypertensive, or Asian, Black, Hispanic, American Indian or Alaska Native, and Native Hawaiian or other Pacific Islander race/ethnicity. (Bottom line: Correlation does not imply causation)
Cunningham JW, Claggett BL, Jering KS, et al. Prognostic Value of Natriuretic Peptides & Cardiac Troponins in COVID-19. Circulation 17 May 2021, https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.054969
Using data from a large health care company, 48,510 inpatients discharged (alive or dead) between April 1 and November 30, 2020 were analyzed for biomarkers at admission. Despite modest levels in most patients with COVID-19, natriuretic peptides and troponin elevation strongly and independently predicted in-hospital death, including in patients without cardiovascular disease. However, the extent to which biomarker levels reflected pre-existing cardiovascular disease or COVID-19 severity remains unclear.
Haghpanah A, Masjedi F, Salehipour M, et al. Is COVID-19 a risk factor for progression of benign prostatic hyperplasia and exacerbation of its related symptoms?: a systematic review. Prostate Cancer Prostatic Dis May 18, 2021. https://www.nature.com/articles/s41391-021-00388-3
Answer: We don’t know (no studies).
Docherty AB, Mulholland RH, Lone NI, et al. Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK. Lancet Resp Med May 14, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00175-2/fulltext
In this large multi-center prospective observational cohort study at 247 acute general hospitals in the UK, patients who were admitted to hospital in March and early April, 2020, were substantially more unwell at presentation than patients who were admitted in later months (June and July 2020). Mortality declined in all age groups, in all ethnic groups, in men and women, and in patients with and without co-morbidities, over and above contributions from declining severity of illness. After adjustment for these variables, a fifth of the reduction in mortality was explained by changes in the use of respiratory support and steroid treatment.
Chou SH, Beghi E, Helbok R, et al. Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19—A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open May 11, 2021. 4(5):e2112131. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779759?resultClick=1
The largest study of neurological manifestations in patients hospitalized with COVID-19. This cohort included 3055 patients with COVID-19 at 28 centers, representing 13 countries and 4 continents. The most prevalent neurological signs and/or syndromes were acute encephalopathy (49%), coma (17%), and stroke (6%), while meningitis and/or encephalitis were rare (0.5%). Neurological symptoms were associated with premature mortality.
McMahon CL, Staples H, Gazi M, et al. SARS-CoV-2 targets glial cells in human cortical organoids. Stem Cell Rep May 11, 2021. Volume 16, ISSUE 5, P1156-1164, May 11, 2021. https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00046-1
SARS-CoV-2 can infect cortical organoids at low titers. There was a preference to glial cells, specifically astrocytes and radial glial progenitor cells. However, replication did not occur.
Chou SH, McWilliams A, Murphy S, et al. Factors Associated With Risk for Care Escalation Among Patients With COVID-19 Receiving Home-Based Hospital Care. Ann Int Med May 11, 2021. https://www.acpjournals.org/doi/10.7326/M21-0409
Home care included 24/7 telephone access to nurses; at least daily in-home visits from paramedics; daily virtual visits with someone at the hospital; and therapies that included intravenous fluids and antibiotics, non-invasive oxygen, and respiratory medications as needed. Results: most patients did not require care escalation, with approximately 1 in 5 admitted within 14 days.
Ram-Mohan N, Zudock EJ, Hashemi MM, et al. SARS-CoV-2 RNAemia predicts clinical deterioration and extrapulmonary complications from COVID-19. Clinical Infectious Diseases 5 May 2021, ciab394, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab394/6265285
In 131 patients, RNAemia was a robust predictor of eventual COVID-19 severity. Initially RNAaemic patients were more likely to manifest severe disease (OR 6.72), worsening of disease severity (OR 2.43), and ICU admission (OR 2.81).
Diao B, Wang C, Wang R, et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection. Nat Commun May 4, 2021, 12, 2506. https://doi.org/10.1038/s41467-021-22781-1
SARS-CoV-2 virus can directly infect human renal cells. Both viral NP and S protein antigens were found in the kidneys from 6 COVID-19 autopsies, accumulating in ACE2+ kidney tubules.
Roth GAA, Emmons-Bell S, Alger HM. Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic. JAMA Netw Open May 3, 2021; 4(5):e218828. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779415?resultClick=1
Again, a learning curve. In this large cohort study, the high rates of in-hospital COVID-19 mortality among US registry patients in March and April 2020 fell by 38% by May and June with a modest further decrease by November. This difference persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity.
Thell R, Zimmermann J, Szell M, et al. Standard blood laboratory values as a clinical support tool to distinguish between SARS-CoV-2 positive and negative patients. Sci Rep 11, 9365 (2021). https://doi.org/10.1038/s41598-021-88844-x
In this large study from Vienna, Austria, leukopenia, eosinopenia, elevated erythrocytes, hemoglobin and ferritin were detected to be among the best standard laboratory parameters to distinguish between COVID-19-positive and -negative patients.
Gao M, Piernas C, Astbury NM, et al. Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study. Lancet Diab Endoc April 28, 2021. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00089-9/fulltext
At a BMI of more than 23 kg/m2, there was a linear increase in risk of severe COVID-19 leading to admission to hospital and death, and a linear increase in admission to an ICU across the whole BMI range, which was not attributable to excess risks of related diseases. The relative risk due to increasing BMI was particularly notable people younger than 40 years and of Black ethnicity.
Rubin GA, Desai AD, Chai Z, et al. Cardiac Corrected QT Interval Changes Among Patients Treated for COVID-19 Infection During the Early Phase of the Pandemic. JAMA Netw Open April 23, 2021;4(4):e216842. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779053
In this cohort study of 965 patients with at least two ECGs, COVID-19 infection was independently associated with significant mean QTc prolongation at days 2 and 5 of hospitalization compared with day 0. The distinctive aspect of this analysis was the inclusion of patients who had negative COVID-19 swabs but continued to receive HCQ and/or azithromycin treatment, which permitted independent analysis of the electrocardiographic association of COVID-19 itself. Of note, 25% of COVID-19 patients receiving neither drug still had a QTc interval of 500 milliseconds or greater.
Broccia MM, de Knegt VE, Mills EH, et al. Household exposure to SARS-CoV-2 and association with COVID-19 severity: a Danish nationwide cohort study. Clinical Infectious Diseases April 24, ciab340, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab340/6248492
Large cohort study from Denmark, revealing that the presence of SARS-CoV-2 positive individuals within households did not pose a higher risk of ‘critical COVID-19’ infection among subsequently infected household members.
Tu TM, Seet CY, Koh JS, et al. Acute Ischemic Stroke During the Convalescent Phase of Asymptomatic COVID-2019 Infection in Men. JAMA Netw Open April 22 2021;4(4):e217498. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779040?resultClick=1
This small cohort from Singapore describes 18 adults 50 years or younger who presented with AIS in the convalescent period of COVID-19 infection. The median (range) time from a positive serological test result to AIS was 54.5 (0-130) days. The findings suggest an increased risk of AIS for these patients even months after a serological diagnosis.
Lebreton G, Schmidt M, Ponnaiah M, et al. Extracorporeal membrane oxygenation network organisation and clinical outcomes during the COVID-19 pandemic in Greater Paris, France: a multicentre cohort study. Lancet Resp Med April 19, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00096-5/fulltext
Of 302 patients on ECMO during the first wave in Paris, 46% were alive at 90 days. During ECMO, 43% had a major bleeding event, 27 of whom had intracranial hemorrhage. Among other well-known factors, treatment in centers that manage at least 30 venovenous ECMO cases annually was independently associated (odds ratio 2.98) with improved 90-day survival.
Dy LF, Lintao RC, Cordero CP, et al. Prevalence and prognostic associations of cardiac abnormalities among hospitalized patients with COVID-19: a systematic review and meta-analysis. Sci Rep 11, 8449 (2021). https://www.nature.com/articles/s41598-021-87961-x
Despite significant heterogeneity in most comparisons, there is a trend towards a definite increase in mortality or severity risk among COVID-19 patients with any cardiac abnormality. Much more long-term prognostic studies are needed as well as to formalize definitive criteria of “COVID-19 associated cardiomyopathy”.
Rossen LM, Branum AM, Ahmad FB, Sutton PD, Anderson RN. Notes from the Field: Update on Excess Deaths Associated with the COVID-19 Pandemic — United States, January 26, 2020–February 27, 2021. MMWR Morb Mortal Wkly Rep 2021;70:570–571. https://www.cdc.gov/mmwr/volumes/70/wr/mm7015a4.htm?s_cid=mm7015a4_w
Best Figure of the day. During January 26, 2020–February 27, 2021, an estimated 545,600–660,200 more persons than expected died in the United States from all causes. Approximately 75%–88% of excess deaths were directly associated with COVID-19. Using weekly historical and provisional mortality data from 2013 through 2021, expected numbers of deaths were estimated using overdispersed Poisson regression models with spline terms to account for seasonal patterns.
Wiegele PN, Kabar I, Kerschke L, Froemmel C, Hüsing-Kabar A, Schmidt H, Vorona E, et al. Symptom diary–based analysis of disease course among patients with mild coronavirus disease, Germany, 2020. Emerg Infect Dis. 2021 May [date cited]. https://doi.org/10.3201/eid2705.204507
Daily prevalence of symptoms in 313 mildly ill COVID-19 outpatients in the first 20 days of illness. Fatigue (91%), cough (85%), and headache (78%) were the most common symptoms and occurred a median of 1 day from symptom onset. Neurological symptoms, such as loss of taste (66%) and anosmia (62%), and dyspnea (51%) occurred considerably later (median 3–4 days after symptom onset).
Finelli L, Gupta V, Petigara T, et al. Mortality Among US Patients Hospitalized With SARS-CoV-2 Infection in 2020. JAMA Netw Open April 8 2021; 4(4):e216556. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2778237?resultClick=1
A learning curve? In this large, nationally representative cohort study on 503,409 (!) patients, in-hospital mortality increased from March to April (10.6% to 19.7%), then decreased significantly to November (9.3%), with significant decreases in all older age groups (> 50 years). The authors speculate that the reasons “may include increased clinical experience in caring for and ventilating patients and use of prone positioning, systemic corticosteroids, and remdesivir”.
Anderson JL, May HT, Knight S, et al. Association of Sociodemographic Factors and Blood Group Type With Risk of COVID-19 in a US Population. JAMA Netw Open April 5, 2021;4(4):e217429. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2778155?resultClick=1
Maybe it’s time to forget the blood group story. In this large, prospective case-control study that included more than 11,000 individuals who were newly infected with SARS-CoV-2, there were no ABO associations with either disease susceptibility or severity. According to the authors, “the smaller sample sizes and retrospective, observational nature of many prior studies, in addition to their striking heterogeneity of ABO associations with disease susceptibility and severity, could be due to chance variations, publication bias, differences in genetic background, geography and environment, and viral strains”.
Roubinian NH, Dusendang JR, Mark DG, et al. Incidence of 30-Day Venous Thromboembolism in Adults Tested for SARS-CoV-2 Infection in an Integrated Health Care System in Northern California. JAMA Intern Med April 5, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2778371?resultClick=1
VTE incidence outside of the hospital is not significantly increased with SARS-CoV-2 infection. This important cohort study includes 220,588 adult members of the Kaiser Permanente Northern California health plan who were tested for SARS-CoV-2 from February 25 through August 31, 2020. Within 30 days of testing, a VTE was diagnosed in 198 (0.8%) positive patients and 1008 (0.5%) patients with a negative result (p < 0.001). Findings argue against the routine use of outpatient thromboprophylaxis as a measure outside of clinical trials.
Lunn MP, Carr AX, Keddie S, et al. Reply: Guillain-Barré syndrome, SARS-CoV-2 and molecular mimicry and Ongoing challenges in unravelling the association between COVID-19 and Guillain-Barré syndrome and Unclear association between COVID-19 and Guillain-Barré syndrome and Currently available data regarding the potential association between COVID-19 and Guillain-Barre syndrome. Brain April 3, 2021. awab070. https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab070/6209732?searchresult=1
Is there a link between GBS and COVID-19? Michael P. Lunn and colleagues are not convinced. They kill their critics with kindness: “We appreciate being cautioned to making a definitive statement of ‘no link’ but would also equally strongly caution against the misuse of small, single studies that are likely to reflect significant well-recognized ascertainment and publication bias. In our view, the dangers of over-feeding the medical literature with unsubstantiated claims about an alarming disease are greater than our self-acknowledged cautionary analysis of COVID-19 causality for GBS.”
Woolf SH, Chapman DA, Sabo RT. Excess Deaths From COVID-19 and Other Causes in the US, March 1, 2020, to January 2, 2021. JAMA April 2, 2021. https://jamanetwork.com/journals/jama/fullarticle/2778361?resultClick=1
Between March 1, 2020, and January 2, 2021, the US experienced 2,801,439 deaths, 22.9% more than expected, representing 522,368 excess deaths. The 22.9% increase in all-cause mortality reported here far exceeds annual increases observed in recent years (≤ 2.5%). Deaths attributed to COVID-19 accounted for 72.4% of US excess deaths.
Ahmad FB, Cisewski JA, Miniño A, Anderson RN. Provisional Mortality Data — United States, 2020. MMWR 31 March 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7014e1.htm?s_cid=mm7014e1_w
In 2020, COVID-19 was the third leading underlying cause of death in the US, replacing suicide as one of the top 10 leading causes of death. The COVID-19 death rate was highest among Hispanics.
Mehta HB, Li S, Goodwin JS. Risk Factors Associated With SARS-CoV-2 Infections, Hospitalization, and Mortality Among US Nursing Home Residents. JAMA Netw Open Mar 31, 2020. 2021;4(3):e216315. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777972?resultClick=1
Retrospective longitudinal cohort study in long-stay residents aged 65 years or older with fee-for-service Medicare insurance residing in 15,038 US nursing homes. Among 137,119 residents (28.4%) diagnosed with SARS-CoV-2 during follow up, 29,204 of them (21.3%) were hospitalized, and 26,384 (19.2%) died within 30 days. For many resident characteristics, there were substantial differences in risk of hospitalization vs mortality, probably representing resident preferences, triaging decisions, or inadequate recognition of risk of death.
Yuan L, Zhu H, Zhou M. et al. Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster. Sig Transduct Target Ther March 30, 6, 136 (2021). https://www.nature.com/articles/s41392-021-00552-0
A gender effect in hamsters: in contrast to males, female animals show much lower shedding viral titers, more moderate symptoms, and relatively mild lung pathogenesis.
Bamidis AD, Koehler P, di Cristanziano V, et al. First manifestation of adult-onset Still’s disease after COVID-19. Lancet Rheumatol 2021, published 26 March. Full text: https://doi.org/10.1016/S2665-9913(21)00072-2
First report of adult-onset Still’s disease (AOSD) showing that long COVID can mimic AOSD and delay diagnosis. The patient was treated with the IL-1 receptor antagonist anakinra (subcutaneous, 100 mg/day).
Klein J, Brito AF, Trubin P, et al. Case Study: Longitudinal immune profiling of a SARS-CoV-2 reinfection in a solid organ transplant recipient. medRxiv 2021, posted 26 March. Full text: https://doi.org/10.1101/2021.03.24.21253992
Patients with solid organ transplantation or those who are otherwise immunosuppressed who recover from infection with SARS-CoV-2, may not develop sufficient protective immunity and are at risk of reinfection.
Molteni E, Astley CM, Ma W, et al. Symptoms and syndromes associated with SARS-CoV-2 infection and severity in pregnant women from two community cohorts. Sci Rep 11, 6928 (2021). https://doi.org/10.1038/s41598-021-86452-3
Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity, except for gastrointestinal symptoms.
Avouac J, Drumez E, Hachulla E, et al. COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study. Lancet Rheumatol 2021, published 25 March. Full text: https://doi.org/10.1016/S2665-9913(21)00059-X
Rituximab therapy is associated with more severe COVID-19 (defined in this study as admission to an ICU or death). Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases.
Lefrancq N, Paireau J, Hozé N, et al. Evolution of outcomes for patients hospitalised during the first 9 months of the SARS-CoV-2 pandemic in France: A retrospective national surveillance data analysis. Lancet Regional Health, March 2021. Full-text: https://doi.org/10.1016/j.lanepe.2021.100087
Better get COVID-19 between waves when hospital capacities are not stretched to the limit. The authors find that both the probability of death and the probability of entering ICU were significantly correlated with COVID-19 ICU occupancy.
Fernández-Prada M, Rivero-Calle I, Calvache-González A, Martinón-Torres F. Acute onset supraclavicular lymphadenopathy coinciding with intramuscular mRNA vaccination against COVID-19 may be related to vaccine injection technique, Spain, January and February 2021. Euro Surveill. 2021;26(10). Full text: https://doi.org/10.2807/1560-7917.ES.2021.26.10.2100193
The authors describe a series of 20 clinical cases with acute onset of single supraclavicular lymphadenopathy coinciding with the ipsilateral intramuscular administration of a dose of an mRNA vaccine.
Altibi AM, Pallavi B, Liaqat H, et al. Characteristics and comparative clinical outcomes of prisoner versus non-prisoner populations hospitalized with COVID-19. Sci Rep 11, 6488 (2021). https://doi.org/10.1038/s41598-021-85916-w
Prisons in the United States have become a hotbed for spreading COVID-19 within said institutions. What about the clinical outcome after hospitalization for COVID-19? You know the answer: prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, in-hospital mortality, and 30-day mortality.
Hansen CH, Michlmayr D, Gubbels SM. Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study. Lancet March 17, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00575-4/fulltext
This large study from Denmark probably provides the best data to date on protection against re-infection. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0.65%) tested positive again during the second surge compared to 16,819 (3.27%) of 514,271 who tested negative during the first surge. Protection against repeat infection was 80.5% (95% CI: 75.4–84.5). Of note, there was no evidence of waning protection over time.
Sheehan MM, Reddy AJ, Rothberg MB, et al. Reinfection Rates among Patients who Previously Tested Positive for COVID-19: a Retrospective Cohort Study. Clinical Infectious Diseases March 15, 2021, ciab234. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab234/6170939
Previous infection appears to offer high levels of protection against symptomatic infection, as well as severe disease, for at least 8 months: in this retrospective cohort study of one multi-hospital health system in Ohio and Florida, protection against symptomatic infection was 84.5% (95% CI: 77.9 to 89.1).
Lambrecq V, Hanin A, Munoz-Musat E, et al. Association of Clinical, Biological, and Brain Magnetic Resonance Imaging Findings With Electroencephalographic Findings for Patients With COVID-19. JAMA Netw Open March 15, 2021. 2021; 4(3):e211489. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777441?resultClick=1
In this retrospective study from Paris, 9/664 (1%) of hospitalized patients presented with brain injury that was defined as COVID-19-related encephalopathy. Six had movement disorders, 7 had frontal syndrome, 4 had brainstem impairment, 4 had periodic EEG discharges, and 3 had MRI white matter–enhancing lesions.
Brehm TT, van der Meirschen M, Hennigs A, et al. Comparison of clinical characteristics and disease outcome of COVID-19 and seasonal influenza. Sci Rep 11, 5803 (2021). https://www.nature.com/articles/s41598-021-85081-0
Again, it’s no flu. Thomas Theo Brehm and colleagues from Hamburg compared 166 patients with COVID-19 diagnosed between February and June 2020, and 255 patients with seasonal influenza diagnosed during the 2017–18 season at the same hospital. Although patients with COVID-19 were younger and had fewer comorbidities, they had a longer duration of hospitalization, a more frequent need of invasive ventilation and were more frequently admitted to the intensive care unit.
Almadhi MA, Abdulrahman A, Alawadhi A, et al. The effect of ABO blood group and antibody class on the risk of COVID-19 infection and severity of clinical outcomes. Sci Rep 11, 5745 (2021). https://doi.org/10.1038/s41598-021-84810-9
In this large study from Bahrein, no association between antibodies and either risk of infection or susceptibility to severe infection was found, possibly indicating that an unexplored underlying factor may be causing the association, not necessarily the blood group or type of antibodies present.
Wohlfahrt J, Fonager J, Albertsen M, et al. Increased Risk of Hospitalisation Associated with Infection with SARS-CoV-2 Lineage B.1.1.7 in Denmark. Lancet Preprints 2021, posted 2 March. Full-text: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3792894
Infection with B.1.1.7 was associated with an increased risk of hospitalization compared with other lineages (adjusted odds ratio: 1.64).
Poletti P, Tirani M, Cereda D, et al. Association of Age With Likelihood of Developing Symptoms and Critical Disease Among Close Contacts Exposed to Patients With Confirmed SARS-CoV-2 Infection in Italy. JAMA Netw Open March 10, 2021;4(3):e211085. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777314
Of 5484 quarantined case contacts who were monitored daily for symptoms for at least 2 weeks, 2824 (51.5%) tested positive. The proportion of infected persons who developed symptoms ranged from 18.1% (95% CI, 13.9%-22.9%) among participants younger than 20 years to 64.6% (95% CI, 56.6%-72.0%) for those aged 80 years or older.
Kompaniyets L, Goodman AB, Belay B, et al. Body Mass Index and Risk for COVID-19–Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death — United States, March–December 2020. MMWR Morb Mortal Wkly Rep. ePub: 8 March 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e4.htm
Among 148,494 US adults with COVID-19, a non-linear “dose response” relationship was found between body mass index and COVID-19 severity, with lowest risks at BMIs near the threshold between healthy weight and overweight in most instances, then increasing with higher BMI. Overweight and obesity were risk factors for invasive mechanical ventilation. Obesity was a risk factor for hospitalization and death, particularly among adults aged < 65 years.
Lugon JC, Smit M, Salamun J, et al. Novel outpatient management of mild to moderate COVID-19 spares hospital capacity and safeguards patient outcome: The Geneva PneumoCoV-Ambu study. PLOS One, March 4, 2021. https://doi.org/10.1371/journal.pone.0247774
Calling patients every 48 hours for the first 10 days following diagnosis, with a standardized interview about self-reported symptoms or every 24 hours if patients presented a worsening clinical condition: this small study in relatively young patients shows that such an outpatient management of mild to moderate COVID-19-related pneumonia is possible. Costly and unnecessary hospitalizations were avoided and hospital capacity was spared.
Wongvibulsin S, Garibaldi BT, Antar AAR, et al. Development of Severe COVID-19 Adaptive Risk Predictor (SCARP), a Calculator to Predict Severe Disease or Death in Hospitalized Patients With COVID-19. Ann Intern Med. 2021 Mar 2. PubMed: https://pubmed.gov/33646849. Full-text: https://doi.org/10.7326/M20-6754
Using longitudinal data from more than 3000 patients hospitalized with COVID-19, the authors have developed a novel tool that can provide dynamic risk predictions for progression from moderate disease to severe illness or death in patients with COVID-19 at any time within the first 14 days of their hospitalization – on the basis of readily available clinical information. Check this out: https://rsconnect.biostat.jhsph.edu/covid_trajectory
Nguyen NT, Chinn J, Nahmias J, et al. Outcomes and Mortality Among Adults Hospitalized With COVID-19 at US Medical Centers. JAMA Netw Open March 5, 2021;4(3):e210417. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777028
The largest US cohort of hospitalized COVID-19 adults to date. Among 192,550 adults hospitalized with COVID-19, 55,593 (28.9%) were admitted to the ICU and 26,221 (13.6%) died during hospitalization. Not surprisingly, in-hospital mortality increased with age; 179 of 12,644 patients (1.4%) aged 18 to 29 years died, and 8277 of 31,135 patients (26.6%) 80 years or older died. Of the patients admitted to the ICU, 15,431 of 55,593 (27.8%) died. The median hospital length of stay among patients who were not admitted to the ICU was 6 days, with a median cost per admission of $10,520. The median hospital length of stay for those admitted to the ICU was 15 days, with a median cost per admission of $39,825. Of note, mortality declined over the course of the 6 month period, from 22.1% in March to 6.5% in August.
Karagiannidis C, Windisch W, McAuley DF, et al. Major differences in ICU admissions during the first and second COVID-19 wave in Germany. Lancet Resp Med March 05, 2021. https://doi.org/10.1016/S2213-2600(21)00101-6
According to Christian Karagiannidis and colleagues who analyzed the data from the federal German hospital payment institute, the data “clearly suggests a dramatic improvement in the management of patients with COVID-19”. Compared with the first wave, 50% fewer of all hospitalized patients were admitted to the ICU during the second wave of the pandemic. By contrast, the prognosis of ICU patients, those requiring mechanical ventilation and those not, remained steady.
Martinez MW, Tucker AM, Bloom J, et al. Prevalence of Inflammatory Heart Disease Among Professional Athletes With Prior COVID-19 Infection Who Received Systematic Return-to-Play Cardiac Screening. JAMA Cardiol March 4 2021; https://jamanetwork.com/journals/jamacardiology/fullarticle/2777308
“The virus challenged me and I defeated it.” That’s what Zlatan Ibrahimovic, famous Swedish soccer player who caught COVID-19 last September, posted on Instagram (you don’t know him? Then please take 94 seconds: https://www.youtube.com/watch?v=GcCVfNA7otY).
“But you are not Zlatan. Do not challenge the virus. Use your head, respect the rules. Social distancing and masks, always. We will win.”
Zlatan was right! But should we have been worried about him? Probably not. In this multicenter, retrospective cross-sectional study of RTP cardiac testing performed on 789 professional athletes with COVID-19 (58% symptomatic, 42% asymptomatic or pauci-symptomatic), imaging evidence of inflammatory heart disease (performed around 3 weeks after positive testing) that resulted in restriction from play was identified in 5 athletes (0.6%) only. No adverse cardiac events occurred in the athletes who underwent cardiac screening and resumed professional sport participation. Thus, with regard to mild COVID-19, there were many Zlatans. On the field, however, there is only one.
Van den Hurk K, Merz EM, Prinsze FJ, et al. Low awareness of past SARS-CoV-2 infection in healthy plasma donors. Cell Reports Med February 25, 2021. https://doi.org/10.1016/j.xcrm.2021.100222
See title. They know nothing. Katja van den Hurk and colleagues asked individuals donating plasma across the Netherlands between May 11th and 18th 2020. Among 3676 with antibody and questionnaire data, 239 (6.5%) were positive for SARS-CoV-2 antibodies. Of those, 48% did not suspect COVID-19 despite the majority reporting symptoms. 11% of seropositive individuals reported no symptims and 27% very mild symptoms at any time during the first peak of the epidemic. Anosmia/ageusia and fever were most strongly associated with seropositivity. Almost 13% of the individuals who tested negative for SARS-CoV-2 did suspect a SARS-CoV-2 infection, a large majority (84%) because of symptoms indicative of COVID-19.
Baldassarri M, Picchiotti N, Fava F, et al. Shorter androgen receptor polyQ alleles protect against life-threatening COVID-19 disease in European males. EBioMedicine. 2021 Feb 26;65:103246. PubMed: https://pubmed.gov/33647767. Full-text: https://doi.org/10.1016/j.ebiom.2021.103246
A genetic polymorphism predisposing some men to develop a more severe disease irrespective of age: in a cohort of 1178 men and women with COVID-19, Margherita Baldassarri from Siena, Italy, and colleagues used a supervised Machine Learning approach on a synthetic representation of genetic variability due to poly-amino acid repeats. Comparing the genotype of patients with extreme manifestations (severe vs. asymptomatic), they found an association between the poly-glutamine repeat number of the androgen receptor (AR) gene, serum testosterone concentrations, and COVID-19 outcome in male patients. Failure of the endocrine feedback to overcome AR signaling defects by increasing testosterone levels during the infection leads to the fact that polyQ ≥ 23 becomes dominant to testosterone levels for the clinical outcome.
Strålin K, Wahlström E, Walther S, et al. Mortality trends among hospitalised COVID-19 patients in Sweden: A nationwide observational cohort study. Lancet Regional Health February 26, 2021 DOI: https://doi.org/10.1016/j.lanepe.2021.100054
There was a gradual decline in mortality during the spring of 2020 in Swedish hospitalised COVID-19 patients. The results remained after adjustment for age, sex, Comorbidities, level of care dependency, country of birth, healthcare region, and SAPS3 (ICU treated patients). Read about the many explanations for this phenomenon. However, the bottom line is that in studies using mortality as an endpoint, the timing of inclusion may play a crucial role regarding outcome. The results of before-and-after studies on specific interventions should be interpreted with caution.
Rodebaugh TL, Frumkin MR, Reiersen AM, et al. Acute symptoms of mild to moderate COVID-19 are highly heterogeneous across individuals and over time. Open Forum Infectious Diseases March 1, ofab090, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab090/6154666
Thomas L. Rodebaugh from St. Louis, US, and colleagues asked 162 participants with acute COVID-19 to respond to surveys up to 31 times for up to 17 days. Several statistical methods were used to characterize the temporal dynamics of these symptoms. Results: the course of symptoms during the initial weeks of COVID-19 is highly heterogeneous and is neither predictable nor easily characterized using typical survey methods. However, the pattern of symptoms over time suggested a fluctuating course for many patients. Participants who showed clinical deterioration were more likely to present with higher reports of severity of cough and diarrhea.
Cavanaugh AM, Thoroughman D, Miranda H, Spicer K. Suspected Recurrent SARS-CoV-2 Infections Among Residents of a Skilled Nursing Facility During a Second COVID-19 Outbreak — Kentucky, July–November 2020. MMWR Morb Mortal Wkly Rep 2021;70:273–277. https://www.cdc.gov/mmwr/volumes/70/wr/mm7008a3.htm?s_cid=mm7008a3_w#suggestedcitation
Five residents of a skilled nursing facility received positive PCR results in two separate COVID-19 outbreaks separated by 3 months. Residents received at least four negative test results between the two outbreaks, suggesting the possibility of reinfection. Severity of disease in the five residents during the second outbreak was worse than that during the first outbreak and included one death.
Cuevas AM, Clark JM, Potter JJ. Increased TLR/MyD88 signaling in patients with obesity: is there a link to COVID-19 disease severity? Int J Obes (Lond). 2021 Feb 26. PubMed: https://pubmed.gov/33637950. Full-text: https://doi.org/10.1038/s41366-021-00768-8
Why is obesity a risk factor for severe COVID-19? The authors review current knowledge and hypothesize that people with obesity, especially excess abdominal/visceral fat and associated metabolic complications, have over-expression of MyD88 in the adipose tissue and perhaps in other cells and tissues (like immune cells) that triggers an exaggerated inflammatory response of the immune system.
van Westen-Lagerweij NA, Meijer E, Meeuwsen EG, et al. Are smokers protected against SARS-CoV-2 infection (COVID-19)? The origins of the myth. npj Primary Care Respiratory Medicine February 26, 2021, volume 31, Article number: 10. https://www.nature.com/articles/s41533-021-00223-1
Do you believe that alcohol disinfects the stomach? Ok, then you don’t need to read any further. For the rest of us, this commentary dispels a few myths (or, if you will, bullsh*t studies) about smoking and COVID-19.
Struyf T, Deeks JJ, Dinnes J, et al. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19. Cochrane Database Syst Rev. 2021 Feb 23;2:CD013665. PubMed: https://pubmed.gov/33620086. Full-text: https://doi.org/10.1002/14651858.CD013665.pub2
Are there signs and symptoms predicting COVID-19? This Cochrane review says no.
Folgueira MD, Luczkowiak J, Lasala F, et al. Prolonged SARS-CoV-2 cell culture replication in respiratory samples from patients with severe COVID-19. Clin Microbiology Inf February 22, 2021. Full-text: https://doi.org/10.1016/j.cmi.2021.02.014
See title. This study from Madrid found a completely different pattern of SARS-CoV-2 viability in upper respiratory tract samples from mild cases, in which viral replication occurs for a short period (10 days), compared with hospitalized patients with severe COVID-19, in whom viable virus can frequently be demonstrated during prolonged periods of up to 4 weeks, both in their upper and lower respiratory tract samples, even in the presence of high levels of neutralizing activity.
Blain H, Gamon L, Tuaillon E, et al. Atypical symptoms, SARS-CoV-2 test results, and immunization rates in 456 residents from eight nursing homes facing a COVID-19 outbreak. Age and Ageing, February 23, 2021, afab050, https://doi.org/10.1093/ageing/afab050
A retrospective longitudinal study in eight NHs with at least ten rRT-PCR-positive residents. Among 456 residents, 161 residents had a positive rRT-PCR (35%), 17% of whom were asymptomatic before testing. Temperature > 37.8°C, oxygen saturation < 90%, unexplained anorexia, behavioral change, exhaustion, malaise, and falls before testing were independent predictors of a further positive rRT-PCR. Hubert Blain and colleagues from France conclude that NH residents with unusual fatigue, behavioral change, anorexia, malaise or falls should be tested by rRT-PCR for an early identification of the first SARS-CoV-2 cases.
Gutiérrez-Gutiérrez B, del Toro MD, Borobia AM, et al. Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study. The Lancet Infectious Diseases February 23, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00019-0/fulltext
Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. Using two large cohorts with more than 3500 patients from Spain, the authors developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes, including a total of 16 variables. Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more Comorbidities and even higher inflammatory parameters than phenotype B. These results might help to better classify patients for clinical management. However, whether the model and derived calculator might be helpful in clinical practice is unknown. Moreover, the pathophysiological mechanisms of the phenotypes must be investigated.
Markewitz R, Torge A, Wandinger KP. et al. Clinical correlates of anti-SARS-CoV-2 antibody profiles in Spanish COVID-19 patients from a high incidence region. Sci Rep 11, 4363 (2021). https://doi.org/10.1038/s41598-021-83969-5
No prognostic value of SARS-CoV-2 antibodies (assessed by the EUROIMMUN assay) in this cohort. Serum samples from 347 Spanish patients from a high-incidence region were collected at one point in time (ranging from 0 to 33 days since onset of symptoms). Neither the presence, nor the levels of antibodies served as prognostic markers. The presence and level of antibodies was not associated with age, sex, duration of hospitalization, treatment in the ICU or death. A subgroup of patients (IgG 4%) did not develop antibodies at the time of sample collection. Compared to the patients that did, no differences were found.
Zhao Y, Cunningham MH, Mediavilla JR, et al. Diagnosis, clinical characteristics, and outcomes of COVID-19 patients from a large healthcare system in northern New Jersey. Sci Rep 11, 4389 (2021). https://doi.org/10.1038/s41598-021-83959-7
In this large cohort of 722 patients from New Jersey, viral load, as indicated by the cycle of threshold (Ct) values from the RT-PCR test, was significantly higher in the oldest patient group (≥ 80), and inversely correlated with survival.
dos Santos LA, Germano de Góis Filho P, Fantini Silva AM, et al. Recurrent COVID-19 including evidence of reinfection and enhanced severity in thirty Brazilian healthcare workers. J Infection, February 12, 2021. DOI:https://doi.org/10.1016/j.jinf.2021.01.020
In 33 patients with recurrent COVID-19 and a positive PCR, recurrence was associated with working as a healthcare professional, blood-group A, and low IgG response to infection. All had recovered from first episode symptoms, returned to work and later suffered recurrent symptoms. Of note, recurrent episodes tended to be more severe, with one fatal infection.
Dai CL, Kornilov SA, Roper RT, et al. Characteristics and Factors Associated with COVID-19 Infection, Hospitalization, and Mortality Across Race and Ethnicity. Clin Infect Dis. 2021 Feb 20:ciab154. PubMed: https://pubmed.gov/33608710. Full-text: https://doi.org/10.1093/cid/ciab154
This retrospective cohort study examining 629,953 patients tested for SARS-CoV-2 in a large US health system, Hispanics who tested positive at a higher rate required excess hospitalization and mechanical ventilation and had higher odds of in-hospital mortality despite younger age.
Schinkel M, Appelman B, Butler J, et al. Association of clinical sub-phenotypes and clinical deterioration in COVID-19: further cluster analyses. Intensive Care Med (2021). February 18, 2021. https://doi.org/10.1007/s00134-021-06363-9
Among patients admitted to ten teaching hospitals across the Netherlands, three sub-phenotypes were identified.
- Sub-phenotype 1 (n = 592) mainly included females (75%, median age 63), characterized by a high prevalence of gastro-intestinal complaints (84%) and sputum production (63%). Comorbidities and medication usage were scarce. The composite outcome of ICU admittance/death rates was relatively low (25%).
- Sub-phenotype 2 (n = 876) included more males (80%, median age 63 years) with few Comorbidities and the lowest medication usage of all three groups. Patients presented with less symptoms than those in sub-phenotype 1, but ICU admittance/death rates were higher (31%).
- Sub-phenotype 3 (n = 551) mostly consisted of older males (80%, median age 76) with multiple Comorbidities, mainly diabetes (62%), hypertension (88%) and other cardiovascular diseases (72%), and consequent medication usage. Patients reported less symptoms such as dyspnea (67%), headache (9%) and myalgia (12%). ICU admission and/or 21-day mortality occurred in 43%.
The authors believe the main value of these sub-phenotypes lies not with their ability to discriminate between clinical outcomes, but in their potential to understand disease heterogeneity and find more homogeneous patient subgroups that may respond more similarly to certain treatments.
Elezkurtaj S, Greuel S, Ihlow J, et al. Causes of death and comorbidities in hospitalized patients with COVID-19. Sci Rep 11, February 19, 2021. https://www.nature.com/articles/s41598-021-82862-5
They die from COVID-19. In 26 decedents who had clinically presented with severe COVID-19, Sefer Elezkurtaj from the Charité in Berlin, Germany, found that septic shock and multi-organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. The majority of patients died of COVID-19 with only contributory implications of pre-existing health conditions.
Bajaj R, Sinclair HC, Patel K. Delayed-onset myocarditis following COVID-19. Lancet Resp Med February 19, 2021. DOI:https://doi.org/10.1016/S2213-2600(21)00085-0. Full text: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00085-0/fulltext
Nine patients with acute cardiac decompensation, negative RT-PCR for SARS-CoV-2, markedly increased serum troponin, and substantially raised inflammatory markers: Retesh Bajaj and colleagues from London suggest that this series describes cardiogenic shock due to a multisystem inflammatory syndrome in adults (MIS-A) after COVID-19.
Pifarré i Arolas H, Acosta E, López-Casasnovas G. et al. Years of life lost to COVID-19 in 81 countries. Sci Rep February 18, 2021. Full-text: https://www.nature.com/articles/s41598-021-83040-3
Some numbers: The total years life lost (YLL) as of January 06, 2021 is 20.507.518. In heavily affected countries this is between 2 and 9 times the median YLL of seasonal influenza or between a quarter and a half of heart disease. Three quarters of the YLL are borne by people dying before age 75. Men have lost 45% more years of life than women.
Lee JT, Hesse EM, Paulin HN, et al. Clinical and Laboratory Findings in Patients with Potential SARS-CoV-2 Reinfection, May-July 2020. Clin Infect Dis. 2021 Feb 18:ciab148. PubMed: https://pubmed.gov/33598716. Full-text: https://doi.org/10.1093/cid/ciab148
Reinfection within 90 days of the initial infection seems to be unlikely. Investigating 73 patients with potential SARS-CoV-2 reinfection in the US in May-July 2020, the authors ruled out reinfection in almost all cases.
Reuken PA, Stallmach A, Pletz MW et al. Severe clinical relapse in an immunocompromised host with persistent SARS-CoV-2 infection. Leukemia February 19, 2021. https://www.nature.com/articles/s41375-021-01175-8
Another case of a female patient with a rituximab-treated B cell lymphoma with severe relapse 4 months after moderate COVID-19. These days, hematologic therapies should be selected with caution, particularly those containing anti-CD20 antibodies.
Purdy A, Ido F, Sterner S, et al. Myocarditis in COVID-19 presenting with cardiogenic shock: a case series. European Heart Journal – Case Reports, Volume 5, Issue 2, 16 February 2021. Full-text: https://academic.oup.com/ehjcr/article/5/2/ytab028/6138217
Adam Purdy and colleagues describe two cases of COVID-19 induced myocarditis presenting with cardiogenic shock. These cases highlight the importance of recognizing late presentation viral myocarditis secondary to COVID-19 infection, even in patients without underlying cardiac disease.
Lecler A, Cotton F, Lersy F, Kremer S, Héran F; SFNR’s COVID Study Group. Ocular MRI Findings in Patients with Severe COVID-19: A Retrospective Multicenter Observational Study. Radiology. 2021 Feb 16:204394. PubMed: https://pubmed.gov/33591889. Full-text: https://doi.org/10.1148/radiol.2021204394
Augustin Lecler et al. report a series of patients with severe COVID-19 presenting with abnormal MRI findings of the ocular globe, showing that 7% of patients with severe COVID-19 presented with one or several nodules of the posterior pole of the globe.
Islam N, Lewington S, Kharbanda RK, et al. Sixty-day consequences of COVID-19 in patients discharged from hospital: an electronic health records study. Eur J Public Health 2021, published 15 February. Full-text: https://doi.org/10.1093/eurpub/ckab009
Among patients discharged following admission for community-acquired COVID-19, there is a high rate of major adverse events, with about 30% of patients re-admitted or dead within 60 days. Nazrul Islam and colleagues followed COVID-19 patients discharged between 15 March and 14 July 2020 from hospitals in Oxfordshire, UK. Rates of re-admission or death were twice as high among those ≥ 65 years as those < 65 years [standardized rate ratio: 2,21 (95% CI: 1,45–3,56)] and among women than men [2,25 (1,05–4,18)].
Pilz S, Chakeri A, Ioannidis JPA, et al. SARS-CoV-2 re-infection risk in Austria. Eur J Clin Invest 2021, published 15 February. Full-text: https://onlinelibrary.wiley.com/doi/pdf/10.1111/eci.13520
In Austria, people with a previous SARS-CoV-2 infection during the first pandemic wave had a 91 percent lower risk of re-infection during the second wave. Stefan Pilz et al. recorded 40 tentative re-infections in 14,840 COVID-19 survivors of the first wave (0.27%) and 253,581 infections in 8,885,640 individuals of the remaining general population (2.85%) translating into an odds ratio (95% confidence interval) of 0.09 (0.07 to 0.13).
Jeffery-Smith A, Iyanger N, Williams SV, et al. Antibodies to SARS-CoV-2 protect against re-infection during outbreaks in care homes, September and October 2020. Euro Surveill. 2021 Feb;26(5):2100092. PubMed: https://pubmed.gov/33541486. Full-text: https://doi.org/10.2807/1560-7917.ES.2021.26.5.2100092
Prior infection with SARS-CoV-2 as determined by antibody or RT-PCR positivity was highly protective at 4 months. Only one re-infection occurred in a seropositive staff member, whose antibodies were boosted following re-infection.
Rha MS, Jeong HW, Ko JH, et al. PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19. Immunity. 2021 Jan 12;54(1):44-52.e3. PubMed: https://pubmed.gov/33338412. Full-text: https://doi.org/10.1016/j.immuni.2020.12.002
More about SARS-CoV-2-specific CD8+ T cells. The highlights: 1) SARS-CoV-2-specific CD8+ T cells are effector memory cells in convalescent individuals; 2) CCR7+CD45RA+ cells are increased among SARS-CoV-2-specific cells in the late phase; 3) SARS-CoV-2-specific CD8+ T cells have fewer IFN-γ+ cells than flu-specific cells; 4) PD-1-expressing SARS-CoV-2-specific CD8+ T cells are not exhausted but functional.
Rentsch CT, Beckman JA, Tomlinson L, et al. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ. 2021 Feb 11;372:n311. PubMed: https://pubmed.gov/33574135. Full-text: https://doi.org/10.1136/bmj.n311
Early initiation of prophylactic anti-coagulation compared with no anti-coagulation among patients admitted to hospital with COVID-19 was associated with a decreased risk of 30-day mortality and no increased risk of serious bleeding events. This is the result of a study of 4297 patients admitted to hospital with COVID-19, 3627 (84,4%) received prophylactic anti-coagulation within 24 hours of admission. More than 99% (n = 3600) of treated patients received subcutaneous heparin or enoxaparin. The cumulative incidence of mortality at 30 days was 14,3% (95% CI: 13,1% to 15,5%) among those who received prophylactic anti-coagulation and 18,7% (15,1% to 22,9%) among those who did not.
Paper of the Day
Davies NG, Jarvis CI, CMMID COVID-19 Working Group, et al. Increased hazard of death in community-tested cases of SARS-CoV-2 Variant of Concern 202012/01. medRxiv 2021, posted 11 February. Full-text: https://doi.org/10.1101/2021.02.01.21250959
Another analysis suggesting that B117 may cause more severe illness. Nicholas Davies et al. analyzed a large database of SARS-CoV-2 community test results and COVID-19 deaths, representing 52% of all SARS-CoV-2 community tests in England from 1 September 2020 to 5 February 2021. The result: among B117 cases, the hazard of death may be more than 50% higher. For a male aged 55–69, the absolute risk of death would increase from 0,6% to 0,9% over the 28 days following a positive test in the community.
Zucman N, Uhel F, Descamps D, Roux D, Ricard JD. Severe reinfection with South African SARS-CoV-2 variant 501Y.V2: A case report. Clin Infect Dis 2021, published 10 February. Full-text: https://doi.org/10.1093/cid/ciab129
Noémie Zucman, Fabrice Uhel and colleagues report a case of severe SARS-CoV-2 reinfection with South African variant 501Y.V2, four months after recovering from a first episode of COVID-19. During the first episode, in September 2020, the 58-year-old man with a history of asthma had mild fever and dyspnea; symptoms resolved within a few days. In January 2021, 129 days after onset of the first infection, he presented to hospital for recurrent dyspnea and fever. Sequencing revealed the B1351 variant. Seven days later, the patient developed a severe acute respiratory distress syndrome requiring intubation and mechanical ventilation.
Tesoriero JM, Swain CE, Pierce JL, et al. COVID-19 Outcomes Among Persons Living With or Without Diagnosed HIV Infection in New York State. JAMA Netw Open. 2021 Feb 1;4(2):e2037069. PubMed: https://pubmed.gov/33533933. Full-text: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775827
Persons living with diagnosed HIV might experience poorer COVID-related outcomes relative to persons living without diagnosed HIV. In this study, previous HIV diagnosis was associated with higher rates of severe disease requiring hospitalization, and hospitalization risk increased with progression of HIV disease stage. Hospitalization risk increased with disease progression to HIV stage 2 (aRR, 1,29 [95% CI: 1,11-1,49]) and stage 3 (aRR, 1,69 [95% CI: 1,38-2,07]) relative to stage 1.
Bellan M, Soddu D, Balbo PE, et al. Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge. JAMA Netw Open. 2021 Jan 4;4(1):e2036142. PubMed: https://pubmed.gov/33502487. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.36142
A consecutive series of 238 patients aged 18 years and older (or their caregivers) who had received a confirmed diagnosis of SARS-CoV-2 infection severe enough to require hospital admission from March 1 to June 29, 2020. (Out of 767 patients, 494 (64,4%) refused to participate, and 35 (4,6%) died during follow-up.) After 4 months, 128/238 patients (53,8%) had functional impairment. Post-traumatic stress symptoms were reported in a total of 41 patients (17,2%).
Daher, A., Balfanz, P., Aetou, M. et al. Clinical course of COVID-19 patients needing supplemental oxygen outside the intensive care unit. Sci Rep 11, 2256 (2021). https://doi.org/10.1038/s41598-021-81444-9
Patients with COVID-19 requiring oxygen therapy need long-term inpatient care with a median of 12 days in hospital including 8 days on supplemental oxygen, which should be taken into account when planning treatment capacity. The authors explain this result by the prolonged inflammatory course of the disease.
Tinelli G, Minelli F, Sica, Tshomba Y. Complete aortic thrombosis in SARS-CoV-2 infection. Eur Heart J 2021, published 26 January. Full-text: https://doi.org/10.1093/eurheartj/ehab011
A 74-year-old man with a history of diabetes mellitus, coronary artery disease, and previous myocardial infarction presents to the emergency department with cardiogenic shock. Three-dimensional computed tomographic (CT) angiography revealed a complete thrombotic occlusion of the aorta. SARS-CoV-2 infection was confirmed by RT-PCR. The patient died immediately after the CT scan.
Figure. Complete thrombotic occlusion of the aorta, arising from the descending aorta and including all the visceral arteries, celiac trunk, superior mesenteric artery, and left and right renal arteries (Panels A). Multifocal ground-glass opacities were visualized in the bilateral lungs (Panels B and C).
Velasquez-Manoff M. What If You Never Get Better From Covid-19? The New York Times 2021, published 21 January. Full-text: https://www.nytimes.com/2021/01/21/magazine/covid-aftereffects.html
Some patients could be living with the after-effects of COVID-19 for years to come. Recent research into another persistent, mysterious disease might help us understand how to treat them.
Kooistra EJ, de Nooijer AH, Claassen WJ et al. A higher BMI is not associated with a different immune response and disease course in critically ill COVID-19 patients. Int J Obes (2021). https://doi.org/10.1038/s41366-021-00747-z
In 67 COVID-19 patients from Nijmegen, Netherlands requiring mechanical ventilation in the ICU, a higher BMI was not related to a different immunological response, unfavorable respiratory mechanics, or impaired outcome. The concentrations and kinetics of clinical inflammatory parameters and respiratory mechanics were similar in both groups.
Lowe KE, Zein J, Hatipoğlu U, et al. Association of Smoking and Cumulative Pack-Year Exposure With COVID-19 Outcomes in the Cleveland Clinic COVID-19 Registry. JAMA Intern Med. Published online January 25, 2021. Full-text: https://doi.org/10.1001/jamainternmed.2020.8360
Time to quit! Among 7102 patients from Cleveland, 6020 (84,8%) were never smokers, 172 (2,4%) were current smokers, and 910 (12,8%) were former smokers. There was a dose-response association between pack-years and adverse COVID-19 outcomes. Patients who smoked more than 30 pack-years had a 2,25 times higher odds of hospitalization (95% CI: 1,76-2,88) and were 1,89 times more likely to die following a COVID-19 diagnosis (95% CI: 1,29-1,76) when compared with never smokers.
Oran DP, Topol EJ. The Proportion of SARS-CoV-2 Infections That Are Asymptomatic: A Systematic Review. Ann Intern Med. 2021 Jan 22. PubMed: https://pubmed.gov/33481642. Full-text: https://doi.org/10.7326/M20-6976
How many are asymptomatic? After screening all observational, descriptive studies and reports of mass screening for SARS-CoV-2 that were either cross-sectional or longitudinal in design published through 17 November 2020 (n = 61), Daniel P. Oran and Eric J. Topol say, “at least one third”.
Pellegrini D, Kawakami R, Guagliumi G, et al. Microthrombi As A Major Cause of Cardiac Injury in COVID-19: A Pathologic Study. Circulation. 2021 Jan 22. PubMed: https://pubmed.gov/33480806. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.051828
Of 40 hearts from deceased COVID-19 patients from Bergamo, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. Notably, 9/14 (64%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. Microthrombi were different in composition as compared to intramyocardial thromboemboli from COVID-19 negative subjects and to coronary thrombi retrieved from COVID-19 positive and negative STEMI patients. Tailored anti-thrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.
Leidman E, Duca LM, Omura JD, Proia K, Stephens JW, Sauber-Schatz EK. COVID-19 Trends Among Persons Aged 0–24 Years — United States, March 1–December 12, 2020. MMWR Morb Mortal Wkly Rep 2021;70:88–94. Full-text: http://dx.doi.org/10.15585/mmwr.mm7003e1
Trends in children and adolescents paralleled trends in adults. Among children, adolescents, and young adults with available data for outcomes, 30.229 (2,5%) were hospitalized, 1973 (0,8%) required ICU admission, and 654 (0,023%) died. You think that this morbidity/mortality is low? Before considering herd immunity, take these numbers and calculate the affected populations in your country.
Ni YN, Wang T, Liang BM, Liang ZA. The independent factors associated with oxygen therapy in COVID-19 patients under 65 years old. PLoS One. 2021 Jan 22;16(1):e0245690. PubMed: https://pubmed.gov/33481912. Full-text: https://doi.org/10.1371/journal.pone.0245690. eCollection 2021
Oxygen therapy is highly required in COVID-19 patients under 65 years old who are admitted to hospital, but the success rate is high: among 833 COVID-19 patients under 65 years old, 29,4% had one or more co-morbidities. Oxygen therapy was required in 63,1%, and the mortality was only 2,9% among the oxygen therapy patients. Respiratory failure-related symptoms, elevated respiratory rate, low albumin and globulin levels, and fever at admission were independent risk factors for the requirement of oxygen.
Paper of the Day
Anesi GL, Jablonski J, Harhay MO, et al. Characteristics, Outcomes, and Trends of Patients With COVID-19-Related Critical Illness at a Learning Health System in the United States. Ann Intern Med. 2021 Jan 19. PubMed: https://pubmed.gov/33460330. Full-text: https://doi.org/10.7326/M20-5327
Is there a learning curve? Among 468 patients with COVID-19–related critical illness admitted to ICUs during the initial surge of the pandemic in the US (from 1 March to 11 May 2020), mortality seemed to decrease over time despite stable patient characteristics. Mortality decreased over time, from 43,5% (95% CI: 31,3% to 53,8%) to 19,2% (CI: 11,6% to 26,7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. Further studies are necessary to investigate causal mechanisms.
Vahidy FS, Pan AP, Ahnstedt H, et al. Sex differences in susceptibility, severity, and outcomes of coronavirus disease 2019: Cross-sectional analysis from a diverse US metropolitan area. PLoS One. 2021 Jan 13;16(1):e0245556. PubMed: https://pubmed.gov/33439908 . Full-text: https://doi.org/10.1371/journal.pone.0245556. eCollection 2021
In this large US cohort, males were more likely to test positive for COVID-19. In hospitalized patients, males were more likely to have complications, require ICU admission and mechanical ventilation, and had higher mortality than females, independent of age.
Song E, Zhang C, Israelow B, et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021 Mar 1;218(3):e20202135. PubMed: https://pubmed.gov/33433624. Full-text: https://doi.org/10.1084/jem.20202135
Evidence for the neuro-invasive capacity of SARS-CoV-2. Akiko Iwasaki, Eric Song and colleagues demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. In autopsies, they also detected SARS-CoV-2 in cortical neurons and noted pathological features associated with infection with minimal immune cell infiltrates.
Bravata DM, Perkins AJ, Myers LJ, et al. Association of Intensive Care Unit Patient Load and Demand With Mortality Rates in US Department of Veterans Affairs Hospitals During the COVID-19 Pandemic. JAMA Netw Open January 19, 2021; 4(1):e2034266. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.34266
Again, flatten the curve! In this cohort study of 8516 patients with COVID-19 admitted to 88 US Veterans Affairs hospitals, strains on critical care capacity were associated with increased COVID-19 mortality. Among patients with COVID-19, those treated in the ICU during periods of peak COVID-19 ICU demand had a nearly 2-fold increased risk of mortality compared with those treated during periods of low demand.
Rubinson L. Intensive Care Unit Strain and Mortality Risk Among Critically Ill Patients With COVID-19—There Is No “Me” in COVID. JAMA Netw Open January 19, 2021;4(1):e2035041. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.35041
Comment: Lewis Rubinson argues that, in light of the important policy implications, additional analyses are urgently needed to investigate whether this association of ICU strain and mortality is causal. If causality is supported, delineation of which care processes are suboptimally provided as ICU load and demand increase will be important to assist hospitals to support them in the hope of reducing the impact of ICU strain on mortality.
Tan CW, Tan JY, Wong WH, et al. Clinical and laboratory features of hypercoagulability in COVID-19 and other respiratory viral infections amongst predominantly younger adults with few comorbidities. Sci Rep 11, January 19, 2021, 1793. Full-text: https://doi.org/10.1038/s41598-021-81166-y
This retrospective cohort study included 182 consecutive COVID-19 and 165 non-CoV-2-respiratory virus patients (median age 37 and 35 years) admitted to Singapore General Hospital. Thrombotic rates were low and comparable in this young and otherwise healthy population. Coagulation parameters did not differ throughout the course of mild COVID-19.
Naveca F, da Costa C, Nascimento V, et al. SARS-CoV-2 reinfection by the new Variant of Concern (VOC) P.1 in Amazonas, Brazil. Virological 2021, posted 18 January. Full-text: https://virological.org/t/sars-cov-2-reinfection-by-the-new-variant-of-concern-voc-p-1-in-amazonas-brazil/596
The lineage P.1 (alias of B.126.96.36.199) is an emerging variant that harbors several amino acid mutations including S:K417T, S:E484K, and S:N501Y. Paola Resende, Felipe Naveca and colleagues describe the first confirmed case of reinfection with the P.1 lineage in a 29-year-old woman in Manaus, Amazonas, Brazil, with no history of immunosuppression, who presented two clinical episodes of COVID-19 infection within a gap of nine months.
Lechien JR, Chiesa-Estomba CM, Beckers E, et al. Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients. J Intern Med. 2021 Jan 5. PubMed: https://pubmed.gov/33403772. Full-text: https://doi.org/10.1111/joim.13209
Olfactory dysfunction (OD) is more prevalent in mild COVID‐19 forms than in moderate‐to‐critical forms. Of 1363 patients, 328 (24,1%) did not subjectively recover olfaction 60 days after the onset of the dysfunction. The mean duration of self‐reported OD was 21,6 ± 17,9 days. The higher baseline severity of objective olfactory evaluations was strongly predictive of persistent OD (p < 0.001).
Marshall M. COVID’s toll on smell and taste: what scientists do and don’t know. Nature 2021, published 14 January. Full-text: https://www.nature.com/articles/d41586-021-00055-6
Almost a year later, some still haven’t recovered their senses of taste and smell, and for a proportion of people who have, odors are now warped: unpleasant scents have taken the place of normally delightful ones. Nature surveys the science behind this potentially long-lasting and debilitating phenomenon.
Starekova J, Bluemke DA, Bradham WS, et al. Evaluation for Myocarditis in Competitive Student Athletes Recovering From Coronavirus Disease 2019 With Cardiac Magnetic Resonance Imaging. JAMA Cardiol. 2021 Jan 14. PubMed: https://pubmed.gov/33443537. Full-text: https://doi.org/10.1001/jamacardio.2020.7444
No need for cardiac magnetic resonance imaging (MRI) to evaluate student athletes recovering from COVID-19? In a study of 145 student athletes with COVID-19 who had mild to moderate symptoms or no symptoms during acute infection, cardiac MRI findings (at a median of 15 days after a positive test result for COVID-19) were consistent with myocarditis in only 2 patients (1,4%), based on updated Lake Louise criteria.
Resende C, Bezerra JF, Teixeira de Vasconcelos RH, et al. Spike E484K mutation in the first SARS-CoV-2 reinfection case confirmed in Brazil, 2020. Virological 2021, posted 10 January. Full-text: https://virological.org/t/spike-e484k-mutation-in-the-first-sars-cov-2-reinfection-case-confirmed-in-brazil-2020/584/1
SARS-CoV-2 strains containing the Spike E484K mutation may be a source of re-infection. The authors describe the case of a 37-year-old woman without pre-existing co-morbidities, a healthcare worker (medical doctor) who had two clinical episodes of COVID-19 (June and October 2020, interval: 116 days). The second infection (with the E484K strain) was mild and evolved without complications like the first episode.
Chen W, Tian Y, Li Z, et al. Potential interaction between SARS-CoV-2 and thyroid: a review. Endocrinology 2021, published 11 January. Full-text: https://doi.org/10.1210/endocr/bqab004
Certain thyroid diseases may have a negative impact on the prevention and control of COVID-19; some anti-COVID-19 agents may cause thyroid injury; and COVID-19 and thyroid disease may mutually aggravate the disease burden.
Editorial. Vitamin D and COVID-19: why the controversy? Lancet Diabetes Endocrinol 2021, published 11 January. Full-text: https://doi.org/10.1016/S2213-8587(21)00003-6
In December, NICE published an updated rapid review of recent studies on vitamin D and COVID-19. Their recommendations: everyone should take vitamin D supplements to maintain bone and muscle health during the autumn and winter months. Later, new guidance from the UK government allowed extremely clinically vulnerable people to opt in to receive a free 4-month supply of daily vitamin D supplements—similar to an initiative launched earlier in Scotland. Several clinical trials on vitamin D and COVID-19 outcomes are underway.
McGonagle D, Bridgewood C, Ramanan AV, Meaney JFM, Watad A. COVID-19 vasculitis and novel vasculitis mimics. Lancet Rheumatology 2021, published 7 January. Full-text: https://doi.org/10.1016/S2665-9913(20)30420-3
In this Viewpoint article, Dennis McGonagle et al. highlight how imaging and post-mortem findings point to a novel vasculitis mimic related to COVID-19 that might lead to cryptogenic strokes across multivessel territories, acute kidney injury with hematuria, a skin vasculitis mimic, intestinal ischemia, and other organ ischemic manifestations.
Solomon T. Neurological infection with SARS-CoV-2 — the story so far. Nat Rev Neurol 2021, published 7 January. Full-text: https://doi.org/10.1038/s41582-020-00453-w
As the COVID-19 pandemic developed and neurological manifestations were reported, concern grew that SARS-CoV-2 might directly invade neuronal cells. However, research throughout the year to address this concern has revealed a different story with inflammatory processes at its center.
Nehme M, Braillard O, Alcoba G, et al. COVID-19 Symptoms: Longitudinal Evolution and Persistence in Outpatient Settings. Ann Intern Med. 2020 Dec 8:M20-5926. PubMed: https://pubmed.gov/33284676. Full-text: https://doi.org/10.7326/M20-5926
In this cohort of 669 persons (mean age 43, 60% women, 24,6% health care workers, 68,8% with no underlying risk factors), symptoms persisted in one third of ambulatory patients 30 to 45 days after diagnosis. Fatigue, dyspnea, and loss of taste or smell were the main persistent symptoms.
Salmon-Ceron D, Slama D, De Broucker T, et al. Clinical, virological and imaging profile in patients with prolonged forms of COVID-19: A cross-sectional study. J Infect. 2020 Dec 4:S0163-4453(20)30762-3. PubMed: https://pubmed.gov/33285216. Full-text: https://doi.org/10.1016/j.jinf.2020.12.002
Cross-sectional mono-center survey on 70 consecutive patients presenting with an initial symptomatic COVID-19 infection who developed prolonged COVID symptoms defined as persistent symptoms (> 2 months after the first day of the initial episode) or resurgent symptoms (at least 3 weeks after the 1st episode). Median age was 45 (range 23–75), 78,6% were female. The authors classify the characteristics of late symptoms in 7 main categories:
- Major fatigue or exhaustion for 51 patients (72,9%)
- Neurological symptoms, in 54 (77,1%), divided into neuro-cognitive disorders (such as memory, mood or attention disorders), headaches, sensory disturbances (such as balance disorders, tingling, burning sensations and neurogenic pains), or others (swallowing or speech disorders, thermoregulation disorders).
- Cardiothoracic symptoms in 50 patients (71,4%): chest pain and tightness, palpitations, cough, dyspnea.
- Muscular or/and articular pains for 20 (25,7%).
- ENT symptoms: persistent or recurrent anosmia, hyposmia and/or dysgeusia for 21 (30%).
- Gastro-intestinal symptoms for 17 (24,3%): diarrhea, nausea/vomiting, epigastric or abdominal pain.
- Skin and vascular symptoms in 10 (14,4%).
Pun BT, Badenes R, La Calle GH, et al. Prevalence and risk factors for delirium in critically ill patients with COVID-19 (COVID-D): a multicentre cohort study. Lancet Respir Health 2021, published 8 January. Full-text: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30552-X/fulltext
Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Now, Brenda Pun, Rafael Badenes and colleagues publish the results of a cohort study on 2088 patients treated in 69 adult intensive care units (ICUs) across 14 countries. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium. The authors conclude that their data present an opportunity to reduce acute brain dysfunction in patients with COVID-19.
Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 2021, 8 January. Full-text: https://doi.org/10.1016/S0140-6736(20)32656-8
At 6 months after acute infection, more than 70% of COVID-19 survivors in Wuhan, China, were troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. This is the result of a cohort study of discharges from Jin Yin-tan Hospital between 7 January and 29 May 2020. Bin Cao, Chaolin Huang and colleagues enrolled 1733 of 2469 discharged patients with COVID-19 (median age 57 years, 52% men). Fatigue or muscle weakness (63%) and sleep difficulties (26%) were the most common symptoms. Anxiety or depression was reported among 23% of patients. 13% of patients without acute kidney injury and with normal eGFR at the acute phase had decreased eGFR at follow-up. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations. See also the comment by Cortinovis M, Perico N, Remuzzi G. Long-term follow-up of recovered patients with COVID-19. Lancet 2021, published 8 January. Full-text: https://doi.org/10.1016/S0140-6736(21)00039-8
Tillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis. 2021 Jan;21(1):52-58. PubMed: https://pubmed.gov/33058797. Full-text: https://doi.org/10.1016/S1473-3099(20)30764-7
Re-infections with SARS-CoV-2 are possible, but don’t seem to be the rule within the first 9 months after the original infection. As a matter of fact, we don’t currently see an epidemic of re-infections in people who were infected during the spring of 2020. Here, Marc Pandori, Richard Tillett and colleagues present the case of a 25-year-old man who presented to health authorities on two occasions with symptoms of viral infection, once at a community testing event in April 2020, and a second time to primary care then hospital at the end of May and beginning of June 2020. The authors show that the patient was infected by SARS-CoV-2 on two separate occasions by a genetically distinct virus.
See also the comment by Iwasaki A. What reinfections mean for COVID-19. Lancet Infect Dis. 2021 Jan;21(1):3-5. PubMed: https://pubmed.gov/33058796. Full-text: https://doi.org/10.1016/S1473-3099(20)30783-0
Rabin R. Some Covid Survivors Haunted by Loss of Smell and Taste. The New York Time 2021, published 2 January. Full-text: https://www.nytimes.com/2021/01/02/health/coronavirus-smell-taste.html
As the coronavirus claims more victims, a once-rare diagnosis is receiving new attention from scientists, who fear it may affect nutrition and mental health. Not peer-reviewed, not even from a medical journal, but worth reading.
Hoehl S, Kreutzer E, Schenk B, et al. Longitudinal testing for respiratory and gastrointestinal shedding of SARS-CoV-2 in day care centres in Hesse, Germany. Clin Infect Dis 2021, published 3 January. Full-text: https://doi.org/10.1093/cid/ciaa1912
Detection of either respiratory or gastrointestinal shedding of SARS-CoV-2 RNA in children and staff members attending day-care centers. This is the result of a longitudinal study over a period of 12 weeks from June to September 2020 to screen children and staff from day-care centers in the state of Hesse, Germany. 859 children (ages 3 months to 8 years) and 376 staff members from 50 day-care centers participated. The authors caution that the study was conducted at a time when activity of other respiratory pathogens was also low in Hesse, Germany, and children with symptoms of upper respiratory infection, other than runny nose only, were excluded from attending day care due to restricts set in place during pandemic.
Heming M. Li X, Räuber S, et al. Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid. Immunity 2020, published 22 December. Full-text: https://doi.org/10.1016/j.immuni.2020.12.011
Neuro-COVID – headache and neuroinflammatory or cerebrovascular disease – are frequent in patients with severe COVID-19. Here, Gerd Meyer zu Hörste, Michael Heming and colleagues identified specific immune alterations in the CSF of neuro-COVID patients featuring an increase of de-differentiated monocytes and exhausted T cells. They observed an IFN response in neuro-COVID that was attenuated compared with viral encephalitis. Severe neuro-COVID exhibited a broad clonal T cell expansion and curtailed IFN response compared with mild neuro-COVID.
Shapiro J, McDonald TB. Supporting Clinicians during Covid-19 and Beyond — Learning from Past Failures and Envisioning New Strategies. N Engl J Med 2020, published 31 December. Full-text: https://doi.org/10.1056/NEJMp2024834
Clinicians are facing important emotional stressors during the COVID-19 pandemic, including grief from seeing so many patients die, fears of contracting the virus and infecting their family members, and anger over health care disparities and other systems failures. Jo Shapiro and Timothy McDonald show the way medical institutions should follow to design emotional-support programs that clinicians will embrace. The last of four suggestions: institutional leadership should be accountable for clinicians’ well-being. Leaders should empower clinicians to speak up about unsafe, highly stressful or morally challenging workplace conditions and ensure that concerns are listened to and, whenever possible, acted on.
Nasomsong W, Luvira V, Phiboonbanakit D. Case Report: Dengue and COVID-19 Coinfection in Thailand. Am J Trop Med Hyg. 2020 Dec 15. PubMed: https://pubmed.gov/33331264. Full-text: https://doi.org/10.4269/ajtmh.20-1340
The authors report a 50-year-old Thai woman who presented with acute high-grade fever, vomiting, and myalgia for 1 day. RT-PCR of the nasopharyngeal swab detected SARS-CoV-2, and RT-PCR of the blood detected dengue virus serotype 2.
Aziz M, Goyal H, Haghbin H, Lee-Smith WM, Gajendran M, Perisetti A. The Association of “Loss of Smell” to COVID-19: A Systematic Review and Meta-Nnalysis. Am J Med Sci. 2020 Nov 1:S0002-9629(20)30427-4. PubMed: https://pubmed.gov/33349441. Full-text: https://doi.org/10.1016/j.amjms.2020.09.017
Patients with olfactory dysfunction or “loss of smell” might have a milder course of the disease. This is the result of a “Systematic Review and Meta-Nnalysis” (sic!) of 51 studies with 11.074 confirmed COVID-19 patients. Let’s hope that the analysis is more accurate than the copy-editor of The American Journal of the Medical Sciences. J
Narang K, Szymanski LM, Kane SV, Rose CH. Acute Pancreatitis in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19). Obstet Gynecol 2020, published 22 December. PubMed: https://pubmed.gov/33355431. Full-text: https://doi.org/10.1097/AOG.0000000000004287
Coronavirus disease 2019 may present in pregnancy with a myriad of clinical symptoms other than respiratory. Acute pancreatitis represents an infrequent complication of primary COVID-19 infection.
Hampshire A. Trender W, Chamberlain SR, et al. Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study. medRxiv 2020, posted 21 October. Full-text: https://doi.org/10.1101/2020.10.20.20215863
SARS-CoV-2 infection may exhibit cognitive deficits that persist into the recovery phase. This is what Adam Hampshire and colleagues from the Imperial College in London suggest after analyzing cognitive test data from 84.285 Great British Intelligence Test participants who completed a questionnaire regarding suspected and biologically confirmed COVID-19 infection. Deficits were most pronounced in individuals who had been hospitalized, but were also detectable in individuals with mild but biologically confirmed cases who reported no breathing difficulty. The scale of the observed deficits was substantial; for the hospitalized patients who needed ventilator support they were equivalent to the average 10-year decline in global performance between the ages of 20 to 70 – comparable to a 8.5-point difference in IQ. Let’s hope that the results of this pre-print paper posted in October will be proved wrong and not be accepted for publication.
Gerkin RC, Ohla K, Veldhuizen MG, et al. Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms. Chemical Senses 2020, published 25 December. Full-text: https://doi.org/10.1093/chemse/bjaa081
Might quantified smell loss be the best predictor of COVID-19 amongst those with symptoms of respiratory illness? That’s the suggestion by Valentina Parma, Richard Gerkin and colleagues after quantifying changes in chemosensory abilities in individuals with a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome.
Woolf SH, Chapman DA, Lee JH. COVID-19 as the Leading Cause of Death in the United States. JAMA December 17, 2020. Full-text: https://doi.org/10.1001/jama.2020.24865
The news media dutifully report each day’s increase in new cases and deaths but putting these numbers in perspective may be difficult. According to CDC data, by October 2020, COVID-19 had become the third leading cause of death for persons aged 45 through 84 years and the second leading cause of death for those aged 85 years or older. Adults 45 years or older were more likely to die from COVID-19 than from chronic lower respiratory disease, transport accidents (eg, motor vehicle fatalities), drug overdoses, suicide, or homicide. Steven H. Woolf and colleagues argue that the daily US mortality rate for COVID-19 deaths is equivalent to the September 11 attacks, which claimed 2988 lives, occurring every 1.5 days, or 19 Airbus 320 jetliners, each carrying 150 passengers, crashing every day.
Piroth L, Cottenet J, Mariet AS, et al. Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study. Lancet Resp Med December 17, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30527-0
No, again, it’s not a flu. This nationwide retrospective cohort study from France included discharge summaries for all hospital admissions, comparing 89.530 patients with COVID-19 and 45.819 patients with influenza. In-hospital mortality was higher in patients with COVID-19 than in patients with influenza (16.9% vs 5.8%), with a relative risk of death of 2.9 (95% CI 2.8–3.0) and an age-standardized mortality ratio of 2.82.
François J, Collery AS, Hayek G, et al. Coronavirus Disease 2019–Associated Ocular Neuropathy With Panuveitis. JAMA Ophthalmol December 17, 2020. Full-text: https://doi.org/10.1001/jamaophthalmol.2020.5695
Case report of an inflammatory ocular neuritis that was associated with uveitis may have been induced by SARS-CoV-2, and resulted in permanent loss of visual acuity. It is notable that although initial disc edema was moderate to mild in this patient, it led to severe atrophy. Other viruses (eg, varicella-zoster virus) have also been reported to have this effect.
Faust JS, Krumholz HM, Du C, et al. All-Cause Excess Mortality and COVID-19–Related Mortality Among US Adults Aged 25-44 Years, March-July 2020. JAMA December 16, 2020. Full-text: https://doi.org/10.1001/jama.2020.24243
According to provisional National Center for Health Statistics data, the COVID-19 pandemic was associated with increases in all-cause mortality among US adults aged 25 to 44 years from March through July of 2020. From March to July, a total of 76.088 all-cause deaths occurred among US adults aged 25 to 44 years, which was 11.899 more than expected (incident rate ratio, 1.19 [95% CI, 1.14-1.23]. Of note, only 38% of all-cause excess deaths were attributed directly to COVID-19, suggesting that COVID-19–related mortality may have been under-detected in this population.
Izurieta HS, Graham DJ, Jiao Y, et al. Natural history of COVID-19: Risk factors for hospitalizations and deaths among >26 million U.S. Medicare beneficiaries. J Infect Dis 16 December 2020. Full-text: https://doi.org/10.1093/infdis/jiaa767
Retrospective cohort study covering Medicare fee-for-service beneficiaries, comparing 653.966 elderly residents in nursing homes (NH) and 292.302 with end-stage renal disease (ESRD) from the primary study population of > 25 million individuals aged ≥ 65. COVID-related death rates (per 10.000) were much higher among elderly NH residents (275,7) and ESRD patients (60,8) than the primary study population (5,0). Regression-adjusted clinical predictors of death among the primary population included immunocompromised status (OR: 1.43), frailty index conditions such as cognitive impairment (3.16) as well as other co-morbidities including congestive heart failure (1.30). Demographic-related risk factors included male sex (1.77), older age (OR: 3.09 for 80-year-old vs. 65-year-old), and racial/ethnic minority.
Soltan ASS, Kouchaki S, Zhu T, et al. Rapid triage for COVID-19 using routine clinical data for patients attending hospital: development and prospective validation of an artificial intelligence screening test. Lancet Digital Health 2020, published 11 December. Full-text: https://doi.org/10.1016/S2589-7500(20)30274-0
The early clinical course of COVID-19 can be difficult to distinguish from other illnesses driving presentation to hospital and PCR testing can take up to 72 h. Here, David Clifton, Andrew Soltan and colleagues from Radcliffe, Oxford, trained linear and non-linear machine learning classifiers to distinguish patients with COVID-19 from pre-pandemic controls. Their models excluded COVID-19 with high-confidence by use of clinical data routinely available within 1 h of presentation to hospital. The authors suggest that their approach could be rapidly scalable, fitting within the existing laboratory testing infrastructure and standard of care of hospitals in high-income and middle-income countries.
Meyerowitz EA, Richterman A, bogoch I, Low N, Cevik M. Towards an accurate and systematic characterisation of persistently asymptomatic infection with SARS-CoV-2. Lancet Infect Dis 2020, published 7 December. Full-text: https://doi.org/10.1016/S1473-3099(20)30837-9
Transmission of SARS-CoV-2 from individuals without symptoms is a major force driving pandemics. Eric Meyerowith and colleagues describe three methodological issues that hinder attempts to estimate the proportion of asymptomatic or pre-symptomatic individuals. First, incomplete symptom assessment may overestimate the asymptomatic fraction; second, studies with inadequate follow-up misclassify pre-symptomatic individuals; and third, serological studies might identify people with previously unrecognised infection, but reliance on poorly defined antibody responses and retrospective symptom assessment might result in misclassification. Discover the answers to these issues.
Interesting case report: on 9 March 2020, male twins from Italy who were 60 years old and considered homozygous because of their appearances and other personal characteristics, were diagnosed with SARS-CoV-2 infection (probably transmitted by the same index patient). Despite a similar viral load at diagnosis, both twins had very different clinical courses (one with mild-to-moderate disease, one with critical COVID-19, requiring mechanical ventilation). Bottom line: everyone is unique (even homozygous twins).
Stavem K, Ghanima W, Olsen MK, Gilboe HM, Einvik G. Persistent symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study. Thorax. 2020 Dec 3:thoraxjnl-2020-216377. PubMed: https://pubmed.gov/33273028. Full-text: https://doi.org/10.1136/thoraxjnl-2020-216377
The authors from Norway conducted a postal survey at the end of June 2020 among non-hospitalized patients, about 1–4 months after the positive PCR test. Of the 451 subjects (48%) who responded to the survey, > 50% (women 53%, men 67%) had no symptoms 1.5–6 months after symptom onset while 16% reported dyspnea, 12% loss/disturbance of smell, and 10% loss/disturbance of taste. Co-morbidities and a high symptom load during the acute phase were associated with persistent symptoms. At 1.5–6 months, however, there was no difference in symptoms according to length of time since COVID-19 onset. Note that these patients were non-hospitalized.
Arnold DT, Hamilton FW, Milne A, et al. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: results from a prospective UK cohort. Thorax. 2020 Dec 3:thoraxjnl-2020-216086. PubMed: https://pubmed.gov/33273026. Full-text: https://doi.org/10.1136/thoraxjnl-2020-21608633271595
Hospitalized patients may differ. In this observational study from the UK, at 8–12 weeks post-admission, 163 survivors were invited to a systematic clinical follow-up. Of 131 participants, 110 attended the follow-up clinic. Most (74%) had persistent symptoms (notably breathlessness and excessive fatigue) and limitations in reported physical ability. However, clinically significant abnormalities in chest radiograph, exercise tests, blood tests and spirometry were less frequent (35%), especially in patients not requiring supplementary oxygen during their acute infection (7%).
Lani-Louzada R, Ramos CDVF, Cordeiro RM, Sadun AA. Retinal changes in COVID-19 hospitalized cases. PLoS One. 2020 Dec 3;15(12):e0243346. PubMed: https://pubmed.gov/33270751. Full-text: https://doi.org/10.1371/journal.pone.0243346
Surprisingly, of the 25 patients with severe or critical disease in this study from Brazil, only three (12%) manifested convincing retinal changes (microhemorrhages, flame-shaped hemorrhage and nerve fiber layer infarcts). These retinal changes were likely secondary to clinical intercurrences or co-morbidities.
Mikuls TR, Johnson SR, Fraenkel L, et al. American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID-19 Pandemic: Version 3. Arthritis Rheumatol. 2020 Dec 5. PubMed: https://pubmed.gov/33277981. Full-text: https://doi.org/10.1002/art.41596
This document provides guidance to rheumatology providers on the management of adult rheumatic disease in the context of the COVID‐19 pandemic.
Cao A, Rohaut B, Guennec LL, et al. Severe COVID-19-related encephalitis can respond to immunotherapy. Brain December 2, 2020. Full-text: https://doi.org/10.1093/brain/awaa337
See title (“can” respond). The authors report a case series of five patients with severe COVID-19-related encephalitis (impaired consciousness/unresponsive and mechanically ventilated) treated by therapeutic plasma exchanges and corticosteroids. The dramatic improvement in three of five patients “reinforces the hypothesis of an immune-related mechanism”.
Mackey K, Ayers CK, Kondo KK. Racial and Ethnic Disparities in COVID-19–Related Infections, Hospitalizations, and Deaths. Annals Int Medicine 1 December 2020. Full-text: https://doi.org/10.7326/M20-6306
Differences in health care access and exposure risk may be driving higher infection and mortality rates. This systematic review revealed that African-American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to co-morbid conditions (low-strength evidence).
Bowles KH, McDonald M, Barró Y. Surviving COVID-19 After Hospital Discharge: Symptom, Functional, and Adverse Outcomes of Home Health Recipients. Ann Int Med 24 November 2020. Full-text: https://doi.org/10.7326/M20-5206
A retrospective observational cohort from New York City, evaluating 1409 patients with COVID-19 admitted to home health care (HHC) between 1 April and 15 June 2020 after hospitalization. After an average of 32 days in HHC, 94% of patients were discharged and most achieved statistically significant improvements in symptoms and function. Eleven patients (1%) died, 137 (10%) were re-hospitalized, and 23 (2%) remain hospitalized. Comorbid conditions of heart failure and diabetes, as well as characteristics present at admission (male gender, white ethnicity), identified patients at greatest risk for an adverse event.
Merello M, Bhatia KP, Obeso JA. SARS-CoV-2 and the risk of Parkinson’s disease: facts and fantasy. Lancet Neurology November 27, 2020. Full-text: https://doi.org/10.1016/S1474-4422(20)30442-7
In this well-balanced review, Marcelo Merello, Kailash Bhatia, Jose Obeso argue that the causal association of SARS-CoV-2 infection with the development of Parkinson’s disease is not supported by robust evidence yet. The authors are concerned about unjustified claims and speculations anticipating a future high incidence of Parkinson’s disease, secondary to the SARS-CoV-2 pandemic. A coordinated international effort to investigate viral effects is essential and should be based on well-designed prospective studies.
Lersy F, Benotmane I, Helms J, et al. Cerebrospinal fluid features in COVID-19 patients with neurologic manifestations: correlation with brain MRI findings in 58 patients. J Infect Dis. 2020 Nov 29:jiaa745. PubMed: https://pubmed.gov/33249438. Full-text: https://doi.org/10.1093/infdis/jiaa745
In this single-center study, the authors describe neurological manifestations in 58 patients, regarding cerebrospinal fluid (CSF) analysis and neuroimaging findings. Protein and albumin levels in CSF were increased in 38% and 23%, respectively. 40% of patients displayed an elevated albumin quotient suggesting impaired blood‐brain barrier integrity. A CSF-specific IgG oligoclonal band was found in five (11%) cases, suggesting an intrathecal synthesis of IgG, and 26 (55%) patients presented identical oligoclonal bands in serum and CSF. Only four (7%) patients harbored a positive SARS-CoV-2 RT-PCR in CSF.
Ioanno GN, Liang P, Locke E, et al. Cirrhosis and SARS‐CoV‐2 infection in US Veterans: risk of infection, hospitalization, ventilation and mortality. Hepatology 21 November 2020. Full-text: https://doi.org/10.1002/hep.31649
Among 88.747 patients tested for SARS‐CoV‐2 between January and mid-May in the US Veterans Affairs (VA) national healthcare system, cirrhosis was associated with a 1,7‐fold increase in mortality in patients with SARS‐CoV‐2 infection.
Pastor-Barriuso PR, Pérez-Gómez B, Hernán MA, et al. Infection fatality risk for SARS-CoV-2 in community dwelling population of Spain: nationwide seroepidemiological study. BMJ 2020, published 27 November. Full-text: https://doi.org/10.1136/bmj.m4509
In this large study from Spain, SARS-CoV-2 infections were derived from the estimated seroprevalence by a chemiluminescent microparticle immunoassay for IgG antibodies in 61.098 participants in the ENE-COVID nationwide survey between 27 April and 22 June 2020. The overall infection fatality risk (IFR) was 0,8% for confirmed COVID-19 deaths and 1,1% for excess deaths. IFR was higher in men than in women (1,1 versus 0,6%). The IFR increased sharply in the elderly age groups, ranging from 1,5% (60-70 years) to 11,6% (80+) in men, and from 0,53 (60-70) to 4,62 (80+) in women.
Wehbe RM, Sheng J, Dutta S, et al. DeepCOVID-XR: An Artificial Intelligence Algorithm to Detect COVID-19 on Chest Radiographs Trained and Tested on a Large US Clinical Dataset. Radiology. 2020 Nov 24:203511. PubMed: https://pubmed.gov/33231531. Full-text: https://doi.org/10.1148/radiol.2020203511
Artificial intelligence (AI) is a significant threat to radiologists and radiology as a specialty. Here, Ramsey Wehbe et al. show that an AI algorithm detected COVID-19 on chest radiographs with a performance similar to a consensus of experienced thoracic radiologists. See also the editorial by van Ginneken B. The Potential of Artificial Intelligence to Analyze Chest Radiographs for Signs of COVID-19 Pneumonia. Radiology. 2020 Nov 24:204238. PubMed: https://pubmed.gov/33236962. Full-text: https://doi.org/10.1148/radiol.2020204238
Bellan M, Patti G, Hayden E, et al. Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients. Sci Rep 10, 20731 (2020). Full-text: https://doi.org/10.1038/s41598-020-77698-4
In March and April 2020, almost 30% of all patients (504/1697) hospitalized in three hospitals in Northern Italy died. In this 126-author paper by Pier Paolo Sainaghi, Mattia Bellan and colleagues, age, a diagnosis of cancer, and the baseline PaO2/FiO2 ratio were independent predictors of mortality.
Hubiche T, Cardo-Leccia N, Le Duff F, et al. Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic. JAMA Dermatol 2020, published 25 November. Full-text: https://doi.org/10.1001/jamadermatol.2020.4324
In this series of 40 consecutive patients with chilblain-like lesions, Thierry Passeron, Thomas Hubiche and colleagues found that none had a positive RT-PCR test, and only 12 (30%) had positive COVID-19 serologic results. Common findings included increased D-dimers, lymphocytic inflammation, vascular damage on skin biopsy results, and a significant interferon-alpha response compared with patients with PCR-positive, acute COVID-19 infection. The authors conclude that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.
Piazza G, Morrow DA. Diagnosis, Management, and Pathophysiology of Arterial and Venous Thrombosis in COVID-19. JAMA. 2020 Nov 23. PubMed: https://pubmed.gov/33226423. Full-text: https://doi.org/10.1001/jama.2020.23422
Thrombotic complications (myocardial infarction, ischemic stroke, venous thromboembolism, etc.) may occur in up to a third of critically ill patients with COVID-19. After a short discussion of the current evidence, Gregory Piazza and David Morrow conclude that thromboprophylaxis should be considered for all hospitalized patients with COVID-19 in the absence of contraindications.
Bilinski A, Emanuel EJ. COVID-19 and Excess All-Cause Mortality in the US and 18 Comparison Countries. JAMA 2020; 324(20):2100-2102. Full-text: https://doi.org/10.1001/jama.2020.20717
Compared with other countries, the US experienced high COVID-19–associated mortality and excess all-cause mortality into September 2020. After the first peak in early spring, US death rates from COVID-19 and from all causes remained exceptionally high. This may have been a result of several factors, including weak public health infrastructure and a decentralized, inconsistent US response to the pandemic.
Fodoulian L, Tuberosa J, Rossier D, et al. SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain. iScience November 24, 2020. Full-text: https://doi.org/10.1016/j.isci.2020.101839
More on anosmia: Leon Fodoulian and colleagues from Geneva, Switzerland asked whether specific cells present in the human olfactory neuroepithelium may represent targets for SARS-CoV-2, by looking at the molecular players involved in infection, both at the RNA and protein levels. They found that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. These cells represent a potential way in for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.
Perrot L, Hemon M, Busnel JM, et al. First flare of ACPA-positive rheumatoid arthritis after SARS-CoV-2 infection. Lancet Rheumatology, November 23, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30396-9
The first definitive case of ACPA-positive rheumatoid arthritis developing after SARS-CoV-2 infection (ie, with samples taken before and after arthritis onset) in a 60-year-old woman from Marseille, France, with infection as a potential trigger for epitope spreading and onset of clinical rheumatoid arthritis symptoms.
Manzano GS, Woods, JK, Amato AA. Covid-19–Associated Myopathy Caused by Type I Interferonopathy. NEJM November 20, 2020. Full-text: https://doi.org/10.1056/NEJMc2031085
Myalgias and elevated creatine kinase levels are seen in many patients. Whether the elevation in creatine kinase level is caused by viral infection of muscle, toxic effects of cytokines, or another mechanism is unclear. Giovanna S. Manzano and colleagues from Boston describe a COVID-19 patient with myopathy who had a muscle-biopsy specimen showing evidence of virus-induced type I interferonopathy.
Van den Borst B, Peters JB, Brink M, et al. Comprehensive health assessment three months after recovery from acute COVID-19. Clin Infect Dis 21 November 2020, ciaa1750. Full-text: https://doi.org/10.1093/cid/ciaa1750
More on “long COVID-19”. All patients discharged after COVID-19 from the Radboud University Medical Centre, Nijmegen, The Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, non-admitted patients with mild disease but with symptoms persisting > 6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest CT/X-ray, 6-minute walk test, body composition, and questionnaires. Among 124 patients (27 mild, 51 moderate, 26 severe and 20 critical), lung diffusion capacity was below the lower limit of normal in 42% of discharged patients, and 22% had low exercise capacity. Problems in mental and/or cognitive function were found in 36% of patients. Health status was generally poor, particularly in the domains of functional impairment (64%), fatigue (69%) and quality of life (72%).
Kennedy M, Helfand BKI, Gou RY, et al. Delirium in Older Patients With COVID-19 Presenting to the Emergency Department. JAMA Netw Open, November 19. 2020;3(11):e2029540. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.29540
In this retrospective cohort study of 817 patients older than 65 years with COVID-19 presenting at emergency departments (ED) of 7 US sites, 28% had delirium at presentation, and delirium was the sixth most common of all presenting signs and symptoms. Among delirious patients, 37% had no typical COVID-19 symptoms or signs, such as cough or fever. Factors associated with delirium (with adjusted relative risk, aRR between 1.1 and 2) were older than 75 years, living in a nursing home or assisted living, had prior use of psychoactive medication, vision impairment, hearing impairment, stroke, and Parkinson’s disease. Not very surprising: delirium was associated with ICU stay (aRR 1.67) and death (aRR 1.24).
Datta SD, Talwar A, Lee JT. A Proposed Framework and Timeline of the Spectrum of Disease Due to SARS-CoV-2 Infection: Illness Beyond Acute Infection and Public Health Implications. JAMA. Published online November 18, 2020. Full-text: https://doi.org/10.1001/jama.2020.22717
Morbidity from SARS-CoV-2 goes beyond acute infection. Amish Talwar, Deblina Datta and James Lee from the CDC propose a framework of three distinct illness periods associated with SARS-CoV-2 infection: 1) acute infection; 2) a rare post-acute hyperinflammatory illness after roughly two weeks; and 3) a stage of late inflammatory and virological sequelae. These illness periods also capture distinct phases of host-viral interaction.
Meduri A, Oliverio GW, Mancuso G, et al. Ocular surface manifestation of COVID-19 and tear film analysis. Sci Rep 10, 20178 (2020). https://doi.org/10.1038/s41598-020-77194-9
No SARS-CoV-2 in tears – that’s the result of a study in 29 hospitalized patients. Ocular symptoms, reported in a third of the patients, included eye burning, foreign body sensation and three reported tearing. Seven patients presented conjunctival hyperemia and/or chemosis, and eleven patients presented blepharitis signs such as lid margin hyperemia and/or telangiectasia, crusted eyelashes, and alterations of the meibomian orifices.
Dhawan R, Gopalan D, Howard L, et al. Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19. Lancet Repiratory Medicine 2020, published 17 October. Full-text: https://doi.org/10.1016/S2213-2600(20)30407-0
The long-term outcomes in survivors of COVID-19 are unknown at present. As pulmonary thrombosis and thromboembolism occur during clinical SARS-CoV-2 infection, the authors propose a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential hemodynamic sequelae that might affect quality of life for a long time.
Bois MC, Boire NA, Layman AJ, et al. COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart. Circulation. 2020 Nov 16. PubMed: https://pubmed.gov/33197204. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.050754
What are the underlying mechanisms of cardiac complications? This small, but detailed histopathologic, immunohistochemical, ultrastructural and molecular cardiac series of 15 COVID-19 cases showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently had cardiac fibrin microthrombi (12/16), without universal acute ischemic injury. Moreover, myocarditis was present in 33.3% of active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
Vaira LA, Hopkins C, Sandison A, et al. Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia. J Laryngol Otol. 2020 Nov 16:1-13. PubMed: https://pubmed.gov/33190655. Full-text: https://doi.org/10.1017/S0022215120002455
Interesting case report of a patient who presented with anosmia persisting for more than three months after infection. MRI did not reveal any pathological findings: the olfactory bulb and clefts were of normal volume, without signal anomalies. However, the biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.
Alvarez-Garcia J, Lee S, Gupta A, et al. Prognostic Impact of Prior Heart Failure in Patients Hospitalized With COVID-19. J Am Coll Cardiol. 2020 Nov 17;76(20):2334-2348. PubMed: https://pubmed.gov/33129663. Full-text: https://doi.org/10.1016/j.jacc.2020.09.549
Retrospective analysis of 6439 patients admitted for COVID-19 at 5 hospitals in New York City between February 27 and June 26, 2020. Compared with patients without heart failure (HF), those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs. 11.9%), and mortality (40.0% vs. 24.9%). Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use.
Coate KC, Cha , Shrestha S. SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Microvasculature and Ducts of Human Pancreas but are Not Enriched in β Cells. Cell Metabolism November 13, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.11.006
Isolated reports of new-onset diabetes in COVID-19 cases have led to the hypothesis that SARS-CoV-2 is directly cytotoxic to pancreatic islet β cells. Katie Coate and colleagues show here that it’s not that easy. In pancreatic sections, ACE2 and TMPRSS2 protein (the main cell entry factors) were not detected in β cells from donors with and without diabetes. Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. Contrasting with previous reports, this careful investigation suggests that the interaction of diabetes and SARS-CoV-2 is mediated by systemic inflammation and/or metabolic changes in other organs such as liver, muscle or adipose tissue (and not by a direct infection of β cells in the pancreas).
Shi Z, de Vries HJ, Vlaar AP, et al. Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers. JAMA Intern Med November 16, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.6278
This study focused on the diaphragm, the main muscle of respiration. Consecutive diaphragm muscle specimens from 26 deceased COVID-19 patients were compared with autopsy diaphragm specimens of 8 patients who had been critically ill without COVID-19. There was an increased expression of genes involved in fibrosis and histological evidence for the development of fibrosis in the diaphragm. Of note, this myopathic phenotype was distinctly different from that of control ICU patients, with comparable duration of mechanical ventilation and ICU length of stay. It is hypothesized that severe myopathy may lead to diaphragm weakness and might contribute to ventilator weaning failure, persistent dyspnea, and fatigue in COVID-19 survivors.
Miller DG, Piesron L, Doernberg S. The Role of Medical Students During the COVID-19 Pandemic. Annals Int Med 2020, November 17. Full-text: https://doi.org/10.7326/L20-1195
Interesting discussion about in-person medical student involvement during the COVID-19 pandemic. Some authors argue for it, others against it. Both sides have good arguments.
Chopra C, Flanders Sa, O’Malley M, et al. Sixty-Day Outcomes Among Patients Hospitalized With COVID-19. Annals Int Med 11 November 2020. Full-text: https://doi.org/10.7326/M20-5661
The toll of COVID-19 extends well beyond hospitalization. In this cohort study of 1648 patients with COVID-19 admitted to 38 hospitals in Michigan, 398 (24%) died during hospitalization and 1250 (76%) survived. Of these, 975 (78%) went home whereas 158 (13%) were discharged to a skilled nursing or rehabilitation facility. By 60 days after discharge, an additional 84 patients (7% of hospital survivors and 10% of ICU-treated hospital survivors) had died. Within 60 days of discharge, 189 patients (15% of hospital survivors) were re-hospitalized. Of patients alive 60 days after discharge, 488 (41.8%) completed a telephone survey. For most patients who survived, ongoing morbidity, including the inability to return to normal activities, physical and emotional symptoms, and financial loss, was common.
Griffith GJ, Morris TT, Tudball MJ, et al. Collider bias undermines our understanding of COVID-19 disease risk and severity. Nat Commun 11, 5749 (2020). Full-text: https://doi.org/10.1038/s41467-020-19478-2
Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, Gareth J. Griffith and colleagues from Bristol highlight the challenge of interpreting observational evidence from such non-representative samples. Read how the collider bias (a variable that is influenced by two other variables, for example when a risk factor and an outcome both affect the likelihood of being sampled) can have a dramatic impact on the results and what approaches are available to explore and mitigate this problem.
Liao X, Wang Y, He Z, et al. Three-month pulmonary function and radiological outcomes in COVID-19 survivors: a longitudinal patient cohort study. Open Forum Infectious Diseases, 14 November 2020. Full-text: https://doi.org/10.1093/ofid/ofaa540
More on “Long COVID-19”. In this study, 172 survivors (33 with severe COVID-19) underwent high resolution CT of the thorax and pulmonary function tests at three months after hospital discharge. An abnormal pulmonary function was found in 11 (6%), and abnormal small airway function (FEF25-75%) in 12 (7%) patients. Obstructive and restrictive ventilation impairment was observed in six (3.5%) patients each. Lung function parameters did not differ between non-severe and severe cases. Of 142 CT scans, 122 (86%) showed residual CT abnormalities and 52 (37%) showed chronic and fibrotic changes.
Choi B, Choudhary MC, Regan J, et al. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. N Engl J Med 2020, published 11 November. Full-text: https://doi.org/10.1056/NEJMc2031364
Under special circumstances, for example in an immunocompromised state, SARS-CoV-2 has the potential for persistent infection and accelerated viral evolution. This is the result of a case report by Manuela Cernadas, Jonathan Li, Bina Choi and colleagues who describe the clinical course of a 45-year-old man with long-standing antiphospholipid syndrome, an autoimmune disorder. Before his death five months after the initial COVID-19 diagnosis, SARS-CoV-2 infection subsided and came back twice.
Wong CKH, Wong JY, Tang EHM, et al. Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis. Sci Rep 10, 19765 (2020). Full-text: https://doi.org/10.1038/s41598-020-74988-9
Meta-analysis of 76 studies published from January-March 2020 on clinical presentation, laboratory findings and treatments of COVID-19 patients, accounting for a total of 11,028 COVID-19 patients. The most common co-morbidities were hypertension (18%), followed by cardiovascular disease (12%) and diabetes (10%). The most frequently identified symptoms were fever (72%) and cough (56%). Notably, 62% and 20% of in-patients received oxygen therapy and non-invasive mechanical ventilation, respectively. In this review, radiological findings of SARS-CoV-2 pneumonia were non-specific.
Meppiel E, Peiffer-Smadja N, Maury A, et al. Neurological manifestations associated with COVID-19: a multicentric registry. Clin Microbiol Infect 2020, published 12 November. Full-text: https://doi.org/10.1016/j.cmi.2020.11.005
Clinical spectrum and outcomes of neurological manifestations associated with SARS-CoV-2 infection may be broad and heterogeneous, suggesting different underlying pathogenic processes. This is the conclusion of a French multicenter study describing 222 patients. The most common neurological diseases were COVID-19 associated encephalopathy (30,2%), acute ischemic cerebrovascular syndrome (25,7%), encephalitis (9,5%), and Guillain-Barré Syndrome (6,8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19 associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré Syndrome.
Lavery AM, Preston LE, Ko JY, et al. Characteristics of Hospitalized COVID-19 Patients Discharged and Experiencing Same-Hospital Readmission — United States, March–August 2020. MMWR Morb Mortal Wkly Rep. ePub: 9 November 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6945e2
Who will be re-admitted? In a cohort of 106,543 patients discharged after an index COVID-19 hospitalization, 9% experienced at least one readmission to the same hospital within 2 months of discharge. Multiple readmissions occurred in 1.6% of patients. Not very surprising: risk factors for readmission included age ≥ 65 years, presence of certain chronic conditions (chronic obstructive pulmonary disease, heart failure, diabetes with chronic complications, chronic kidney disease, and obesity), hospitalization within the 3 months preceding the first COVID-19 hospitalization, and discharge to a skilled nursing facility or with home health care.
Avanzato VA, Matson MJ, Seifert SN, et al. Case Study: Prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised cancer patient. Cell November 04, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.10.049
Immunocompromised patients may shed infectious virus for longer durations than previously recognized: Victoria Avanzato and colleagues describe an interesting case of a female immunocompromised patient with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Shedding of infectious SARS-CoV-2 was observed for up to 70 days.
Santos-Ferreira D, Tomás R, Dores H. Return-to-Play Guidelines for Athletes After COVID-19 Infection. JAMA Cardiol. November 4, 2020. Full-text: https://doi.org/10.1001/jamacardio.2020.5345
What to do with athletes after recovery? The clinical implications of asymptomatic to mild COVID-19 still remain undetermined. Pulmonary and cardiac fibrosis are potentially the most relevant for athletes, which may lead to reduced lung capacity or cardiac dysfunction, malignant arrhythmias, and sudden death. Complications from the disease must be excluded prior to returning to play. According to the authors, those with suspected or confirmed COVID-19 (including mild or complicated disease) or presenting with suggestive signs or symptoms should undergo additional investigations according to presentation and disease severity. These may include blood tests, electrocardiography, echocardiography, 24-hour and/or 48-hour Holter monitoring, exercise testing, or lung function tests.
Smilowitz NR, Jethani N, Chen J, et al. Myocardial Injury in Adults Hospitalized with COVID-19. Circulation 5 Nov 2020. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.050434
Nathaniel R. Smilowitz and colleagues have analyzed myocardial injury at admission and during hospitalization in a large cohort of 2163 patients with COVID-19 from a high-volume health care system in New York. Nearly a third (32%) had myocardial injury at presentation, and nearly half had injury detected during the course of their hospitalization. Regardless of when it was first detected, myocardial injury was associated with increased odds of mortality and critical illness, with higher cardiac Troponin (cTn) measurements associated with worse outcomes.
Zhong P, Xu J, Yang D, et al. COVID-19-associated gastrointestinal and liver injury: clinical features and potential mechanisms. Sig Transduct Target Ther 5, 256 (2020). Full-text: https://doi.org/10.1038/s41392-020-00373-7
Besides common respiratory symptoms, some patients with COVID-19 experience gastrointestinal symptoms, such as diarrhea, nausea, vomiting, and loss of appetite. In this review, Yangbai Sun, Peijie Zhong and colleagues highlight the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19.
Gandhi RT, Lynch JB, del Rio C. Mild or Moderate Covid-19. N Engl J Med, October 29, 2020; 383:1757-1766. Full-text: https://doi.org/10.1056/NEJMcp2009249
Brief overview for clinicians. In patients with moderate disease, dexamethasone is not efficacious (and may be harmful) and data are insufficient to recommend for or against routine use of remdesivir. Efforts center on personal protective equipment for health care workers, social distancing, and testing.
Giustino G, Croft LB, Stefanini GG, et al. Characterization of Myocardial Injury in Patients With COVID-19. J Am Coll Cardiol. 2020 Nov 3;76(18):2043-2055. PubMed: https://pubmed.gov/33121710. Full-text: https://doi.org/10.1016/j.jacc.2020.08.069
This multicenter cohort study (7 hospitals in New York City and Milan) analyzed hospitalized COVID-19 patients who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. Overall, myocardial injury was observed in 190 patients (62.3%). Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities.
Hoffmann C, Wolf E. The Low Case Fatality Rate of COVID-19 in Hong Kong Could Be Deceptive. Clin Infect Dis. 2020 Oct 29:ciaa1676. PubMed: https://pubmed.gov/33119056 . Full-text: https://doi.org/10.1093/cid/ciaa1676
Last Monday, we published data from the 20 most affected European countries and the USA and Canada, showing that during the first wave of the pandemic, the variance of crude CFR of COVID-19 was predominantly (80-96%) determined by the proportion of older individuals who are diagnosed with SARS-CoV-2 (Hoffmann 2020).
Here we show that our model might apply to other countries. In Hong Kong, for example, a very low CFR of only 0.4% has been reported during the first weeks (Lui GC 2000). In contrast to the authors, we believe that this was mainly due to the low number of older persons among the confirmed SARS-CoV-2 cases. We also show that the overall CFR in Hong Kong has increased since then, paralleling the increasing proportion of older persons among confirmed cases. Thanks to the incredible speed of Clinical Infectious Diseases’ publishing policies (contrasting many other journals), the authors from Hong Kong have been already able to respond (in some points they agree, in other points they don’t). Please read the discussion (Lui GC 2000).
Why is this important? In many countries facing a low CFR during the first wave, there is a widespread feeling that this was mainly due to a good health care system such as ICU or testing capacities. We believe that this perception can be deceptive and that the picture in these countries will change immediately when more elderly people are infected.
Hoffmann C, Wolf E. Older age groups and country-specific case fatality rates of COVID-19 in Europe, USA and Canada. Infection. 2020 Oct 24:1-6. PubMed: https://pubmed.gov/33098532 . Full-text: https://doi.org/10.1007/s15010-020-01538-w
Lui GC, Yip TC, Wong VW, et al. Significantly Lower Case-fatality Ratio of Coronavirus Disease 2019 (COVID-19) than Severe Acute Respiratory Syndrome (SARS) in Hong Kong-A Territory-Wide Cohort Study. Clin Infect Dis. 2020 Oct 1:ciaa1187. PubMed: https://pubmed.gov/33005933. Full-text: https://doi.org/10.1093/cid/ciaa1187
Lui CG, Yip TC, Hui D, et al. Reply to Hoffmann and Wolf. Clinical Infectious Diseases, October 29, ciaa1678, https://doi.org/10.1093/cid/ciaa1678.
Lim ZJ, Subramaniam A, Reddy MP, et al. Case Fatality Rates for COVID-19 Patients Requiring Invasive Mechanical Ventilation: A Meta-analysis. Am J Respir Crit Care Med. 2020 Oct 29. PubMed: https://pubmed.gov/33119402 . Full-text: https://doi.org/10.1164/rccm.202006-2405OC
Definitive hospital outcome on 13,120 patients receiving invasive mechanical ventilation. Among studies where age-stratified CFR was available, pooled CFR estimates ranged from 47.9% (95% CI 46.4-49.4%) in younger patients (age ≤40) to 84.4% (95% CI 83.3-85.4) in older patients (age >80). CFR was also higher in early COVID-19 epicenters.
Prieto-Alhambra D, Balló E, Mora N, et al. Filling the gaps in the characterization of the clinical management of COVID-19: 30-day hospital admission and fatality rates in a cohort of 118 150 cases diagnosed in outpatient settings in Spain. International Journal of Epidemiology, October 29, 2020, dyaa190. Full-text: https://doi.org/10.1093/ije/dyaa190
Filling the missing link in the natural history of COVID-19, from first (usually milder) symptoms to hospitalization and/or death, the authors characterized a huge number of COVID-19 patients at the time at which they were diagnosed in outpatient settings and estimated 30-day hospital admission and fatality rates. In the month after diagnosis, 14.8% (14.6–15.0) were hospitalized, with a greater proportion of men and older people, peaking at age 75–84 years. Thirty-day fatality was 3.5%, higher in men, increasing with age and highest in those residing in nursing homes (24.5%).
Kim T, Roslin M, Wang JJ, et al. Body Mass Index as a Risk Factor for Clinical Outcomes in Patients Hospitalized with COVID-19 in New York. Obesity (Silver Spring). 2020 Oct 31. PubMed: https://pubmed.gov/33128848 . Full-text: https://doi.org/10.1002/oby.23076
Risk factor obesity. In total, 10,861 COVID‐19 patients admitted to the Northwell Health system hospitals during March and April, were classified according to their BMI: underweight (2%), normal (only 23%!), overweight (38%), obesity class I (22%), II (9%), and III (7%). Patients who were overweight (OR=1.27), obesity class I (OR=1.48), obesity class II (OR=1.89), and obesity class III (OR=2.31) had increased risk of requiring invasive mechanical ventilation. Overall, underweight and obesity classes II and III were statistically associated with death (OR=1.25-1.61). However, once mechanically ventilated, all patients regardless of BMI had similar odds of death.
Fajnzylber J, Regan J, Coxen K, et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun 11, 5493 (2020). https://doi.org/10.1038/s41467-020-19057-5
SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. This is the result of a study by Jonathan Li, Jesse Fajnzylber and colleagues who report SARS-CoV-2 respiratory tract, plasma, and urine viral loads of 235 participants who were either hospitalized with COVID-19 (n=88), evaluated as symptomatic outpatients (n=94), or had recovered from COVID-19 disease (n=53). The prevalence of SARS-CoV-2 plasma viremia in hospitalized individuals with severe disease was relatively high, but plasma viremia was also detected in symptomatic non-hospitalized participants. Compared to individuals who were discharged from the hospital, those who eventually died had significantly higher levels of plasma viremia at the time of initial sampling (median plasma viral load 1.0 vs 2.0 log10 RNA copies/mL). For hospitalized individuals with initial detectable viremia, 32% died vs. 8% of those without initial viremia (odds ratio (OR) 5.5).
An C, Lim H, Kim D, et al. Machine learning prediction for mortality of patients diagnosed with COVID-19: a nationwide Korean cohort study. Sci Rep 10, 18716 (2020). Full-text: https://doi.org/10.1038/s41598-020-75767-2
At the height of pandemic waves, healthcare services may be overwhelmed by huge numbers of patients. Here, the authors propose a prediction model which might be helpful for the quick triage of patients without having to wait for the results of additional tests such as laboratory or radiologic studies. They demonstrate that machine learning models utilizing sociodemographic characteristics and medical history might accurately predict the prognosis of COVID-19 patients after diagnosis. Their models predicted not only the final outcome (i.e., mortality vs. recovery) but also early mortality (i.e., 14- or 30-day mortality).
Brandén M, Aradhya S, Kolk M, et al. Residential context and COVID-19 mortality among adults aged 70 years and older in Stockholm: a population-based, observational study using individual-level data. Lancet Healthy Longevity 2020, published 27 October. Full-text: https://doi.org/10.1016/S2666-7568(20)30016-7
Living in a care home is associated with increased mortality – we knew that. Living in neighborhoods with high population density (≥ 5000 individuals per km2) is associated with higher COVID-19 mortality (1·7; 1·1–2·4) compared with living in less densely populated neighborhoods (0 to < 150 individuals per km2) – we knew that, too. Living with someone of working age (< 66 years), when compared with living in a household with individuals aged 66 years or older, was associated with increased COVID-19 mortality (hazard ratio 1·6; 95% CI 1·3–2·0). We imagined that. It was reported by Maria Brandén and colleagues after analyzing 274,712 individuals aged 70 years or older and residing in Stockholm. See also the comment by Roxby AC, Gure TR: Lessons from Sweden: where can older adults shelter from COVID-19? Lancet Healthy Longevity 2020, published 27 October. Full-text: https://doi.org/10.1016/S2666-7568(20)30035-0
Clift AK, Coupland CAC, Keogh RH, Hemingway H, Hippisley-Cox J. COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study Of 8 Million Adults. Ann Intern Med. 2020 Oct 21. PubMed: https://pubmed.gov/33085509. Full-text: https://doi.org/10.7326/M20-4986
Persons with Down syndrome seem to be at an increased risk for COVID-19–related hospitalization and death. This is the result of an analysis of individual-level data in a cohort study of 8,26 million adults in the UK. The authors estimate a 4-fold increased risk for COVID-19–related hospitalization and a 10-fold increased risk for COVID-19–related death.
Car J, Koh GCH, Foong PS, Wang J. Video consultations in primary and specialist care during the covid-19 pandemic and beyond. BMJ 2020; 371. Full-text: https://doi.org/10.1136/bmj.m3945
At the start of the pandemic, many GPs and specialists turned to video consultations to reduce patient flow through healthcare facilities and limit infectious exposures. What was your experience? Josip Car and colleagues give you a grand tour of video consultations in the COVID-19 era: how to start, how to prepare patients for the consultation, suggestions for a remote physical examination, and how to switch from a video to a telephone or in-person consultation, depending on technical, patient, or clinical factors. A must-read for GPs.
Clift AK, Keogh RH, Diaz-Ordaz K, et al. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. BMJ 2020, published 20 October. Full-text: https://doi.org/10.1136/bmj.m3731
Julia Hippisley-Cox, Ash Clift and colleagues present a new risk tool to predict a person’s risk of being admitted to hospital and dying from COVID-19. They used data from 6 million patients over a 97-day period (24 January to 30 April 2020), and a further 2.2 million patients to validate its performance over two separate time periods (24 January to 30 April 2020 and 1 May to 30 June 2020). People in the top 5% for predicted risk of death accounted for 76% of COVID-19 deaths within the 97-day study period while people in the top 20% accounted for 94% of COVID-19 deaths. We are now waiting for the model to become freely available on the internet.
See also the comment by Matthew Sperrin: Prediction models for covid-19 outcomes. BMJ 2020, published 20 October. Full-text: https://doi.org/10.1136/bmj.m3777
di Filippo L, Formenti AM, Doga M, et al. Radiological Thoracic Vertebral Fractures are highly prevalent in COVID-19 and predict disease outcomes. J Clin Endocrinol Metabol 2020, published 21 October. Full-text: https://doi.org/10.1210/clinem/dgaa738
In this retrospective cohort study from a tertiary health-care hospital in Northern Italy, 114 SARS-CoV-2 positive patients were included. Thoracic vertebral fractures (VF) were detected in 41 patients (36%). Patients with VFs required more frequently a non-invasive mechanical ventilation compared to those without VFs (p = 0.02). Mortality was 22% in VFs+ group and 10% in VFs- group (p = 0.07). In particular, mortality was higher in patients with severe VFs compared to those with moderate and mild VFs (p = 0.04). The authors conclude that VF might be a useful and easy-to-measure clinical marker of fragility and poor prognosis and suggest that morphometric thoracic vertebral evaluation should be performed in all suspected COVID-19 patients undergoing chest X-rays.
Hudowenz O, Klemm P, Lange U, et al. Case report of severe PCR-confirmed COVID-19 myocarditis in a European patient manifesting in mid January 2020. European Heart Journal – Case Reports. Full-text: https://doi.org/10.1093/ehjcr/ytaa286
A positive polymerase chain reaction (PCR) test of SARS-CoV-2 in heart specimens: the authors present a case of severe COVID-19 myocarditis manifesting in mid-January 2020. Primarily suspected of being related to small-vessel vasculitis, the case was later revised to COVID-associated disease when the patient reported a history of travel to Tyrol. Consequently, PCR testing resulted positive in a previously obtained heart specimen. The immunosuppressive treatment was discontinued. During a follow-up visit at the end of April, the patient’s recovery was stable.
Yang W, Kandula S, Huynh M, et al. Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis. Lancet Infect Dis 2020, published 19 October. Full-text: https://doi.org/10.1016/S1473-3099(20)30769-6
The infection-fatality risk (IFR) is the risk of death among all infected individuals including those with asymptomatic and mild infections. Here, Wan Yang and colleagues report on the outcome of SARS-CoV-2 infection during the first wave in New York City. They found an overall IFR of 1.39%. Age was the all-important factor: 25–44 years: 0.11%; 45–64 years: 0.94%; 65-74 years: 4.9%; 75 years and older: 14.2%. The sample size reported is impressive: 205,639 people with laboratory-confirmed SARS-CoV-2, and 21,447 confirmed and probable COVID-19-related deaths.
Pimenoff VN, Elfström M, Baussano I, et al. Estimating total excess mortality during a COVID-19 outbreak in Stockholm, Sweden. Clinical Infectious Diseases. Full-text: https://doi.org/10.1093/cid/ciaa1593
Ville Pimenoff estimates that since January 2020, the accumulated excess mortality in the Stockholm region at week 18 was +23% compared with the average over the previous ten years. Of note, comparison with the number of reported COVID-19-related deaths in the 5 week peak period of the outbreak found that 26% of the excess mortality during the COVID-19 epidemic was not recognized as COVID-19-related, either via public health data or by the regional morgue.
Lu QB, Zhang Y, Liu MJ , et al. Epidemiological parameters of COVID-19 and its implication for infectivity among patients in China, 1 January to 11 February 2020. Euro Surveill. 2020;25(40). Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.40.2000250
Using a large database of > 2000 COVID-19 cases and potential transmission pairs of cases, the authors estimate the median incubation period to be 7.2 (95% confidence interval: 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Pediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007).
Kontis V, Bennett JE, Rashid T, et al. Magnitude, demographics and dynamics of the effect of the first wave of the COVID-19 pandemic on all-cause mortality in 21 industrialized countries. Nat Med (2020). Full-text: https://doi.org/10.1038/s41591-020-1112-0
The total death toll for the first wave of the COVID-19 pandemic for 21 industrialized countries (not including US or Germany). England, Wales and Spain experienced the largest effect: ~100 excess deaths per 100,000 people, equivalent to a 37% (30–44%) relative increase in England and Wales and 38% (31–45%) in Spain.
Bilinski A, Emanuel EJ. COVID-19 and Excess All-Cause Mortality in the US and 18 Comparison Countries. JAMA October 12, 2020. Full-text: https://doi.org/10.1001/jama.2020.20717
Alyssa Bilinski and Ezekiel Emanuel have compared 14 countries with all-cause mortality data, finding similar patterns. In countries with moderate COVID-19 mortality, excess all-cause mortality remained negligible throughout the pandemic. In countries with high COVID-19 mortality, excess all-cause mortality reached as high as 102/100,000 in Spain, while in the US it was 72/100,000. However, since May, excess all-cause mortality was higher in the US than in all high-mortality countries, due possibly to several factors, including weak public health infrastructure and a decentralized, inconsistent US response to the pandemic.
Gold JA, Rossen LM, Ahmad FB, et al. Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19 — United States, May–August 2020. MMWR Morb Mortal Wkly Rep. ePub: 16 October 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6942e1
This report provides information on how demographic and geographic factors have changed among COVID-19–associated deaths during May–August 2020. Of 114,411 COVID-19–associated deaths, 51% of decedents were non-Hispanic White, 24% were Hispanic or Latino (Hispanic), and 19% were non-Hispanic Black. The percentage of Hispanic decedents increased from 16.3% in May to 26.4% in August. Data suggest that the geographic shift from the Northeast to the South and West alone does not entirely account for this increase.
Mascitti H, Bonsang B, Dinh A, et al. Clinical cutaneous features of patients infected with SARS-CoV-2 hospitalized for pneumonia: a cross-sectional study. Open Forum Infectious Diseases, 18 October 2020. Full-text: https://doi.org/10.1093/ofid/ofaa394
Various dermatological signs were seen in 59 COVID-19 patients, a macular rash being the most frequent. All cutaneous features could be related to a vascular leak process.
Liotta EM, Batra A, Clark JR, et al. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Ann Clin Transl Neurol. 2020 Oct 5. PubMed: https://pubmed.gov/33016619. Full-text: https://doi.org/10.1002/acn3.51210
Is encephalopathy independently associated with higher mortality in hospitalized patients with COVID-19? That’s the conclusion of a study of 509 consecutive patients admitted within a hospital network in Chicago between 5 March and 6 April 2020. The increased mortality, independent of respiratory severity, parallels previous reports about sepsis‐associated encephalopathy and delirium‐associated mortality. The authors recognize the limitations of a retrospective study. Keep an eye on the subject.
Matschke J, Lütgehetmann M, Hagel C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurology, October 5, 2020. Full-text: https://doi.org/10.1016/S1474-4422(20)30308-2
Jakob Matschke and colleagues from Hamburg, Germany have investigated the neuropathological features in the brains of 43 patients who died from COVID-19. Neuropathological changes seemed to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients but was not associated with the severity of neuropathological changes.
Frontera JA, Sabadia S, Lalchan R, et al. A Prospective Study of Neurologic Disorders in Hospitalized COVID-19 Patients in New York City. Neurology. 2020 Oct 5:10.1212/WNL.0000000000010979. PubMed: https://pubmed.gov/33020166. Full-text: https://doi.org/10.1212/WNL.0000000000010979
Of 4,491 hospitalized COVID-19 patients, 606 (13.5%) developed a new neurologic disorder. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%, temporary/reversible changes in mental status in the absence of focal neurologic deficits or primary structural brain disease, excluding patients in whom sedative or other drug effects or hypotension explained this), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. In-hospital mortality was increased for patients with neurological disorders (Hazard Ratio 1.38, 95% CI 1.17-1.62).
Schwartz A, Yogev Y, Zilberman A, et al. Detection of SARS-CoV-2 in vaginal swabs of women with acute SARS-CoV-2 infection: a prospective study. BJOG. 2020 Oct 5. PubMed: https://pubmed.gov/33021026. Full-text: https://doi.org/10.1111/1471-0528.16556
In this prospective study of 35 women who were diagnosed with acute SARS‐CoV‐2 infection by a nasopharyngeal RT‐PCR test, vaginal RT‐PCR swabs were positive in 2 (5.7%). One was pre‐menopausal and the other was a post‐menopausal woman. Both women had mild disease.
Grasselli G, Greco M, Zanella A, et al. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med 2020; 180(10):1345-1355. Full-text: https://doi.org/10.1001/jamainternmed.2020.3539
An update from Lombardy, Italy. This large retrospective observational cohort study included 3,988 consecutive critically ill patients referred for ICU admission until April 22, 2020. Median age was 63 (IQR 56-69) and 79.9% were men. At ICU admission, 87.3% required invasive mechanical ventilation (IMV). The median length of IMV was 10 (IQR, 6-17) days. In the subgroup of the first 1,715 patients, as of May 30, 2020, 836 (48.7%) died in the ICU. Independent risk factors associated with mortality included older age (hazard ratio 1.75), male sex (1.57), high fraction of inspired oxygen (1.14), high positive end-expiratory pressure (1.04) and history of chronic obstructive pulmonary disease (1.68), hypercholesterolemia (1.25), and type 2 diabetes (1.18).
Morris SB, Schwartz NG, Patel P, et al. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep. ePub: 2 October 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6940e1
MIS-C (multisystem inflammatory syndrome in children) in adults? The authors report a multisystem inflammatory syndrome in adults (MIS-A), describing 27 patients who had cardiovascular, gastrointestinal, dermatologic, and neurologic symptoms without severe respiratory illness. The authors call for clinicians to consider MIS-A in adults with compatible signs and symptoms. Recall that these patients may not have positive SARS-CoV-2 PCR or antigen test results; antibody testing might be needed to confirm previous SARS-CoV-2 infection.
Alvarado GR, Pierson BC, Teemer ES, et al. Symptom Characterization and Outcomes of Sailors in Isolation After a COVID-19 Outbreak on a US Aircraft Carrier. JAMA Netw Open. October 1, 2020. 2020;3(10):e2020981. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.20981
The US Army Public Health COVID-19 Task Force describes the results of an independent investigation of the shore-based USS Theodore Roosevelt outbreak response. Of 4,085 sailors who disembarked, 736 had a diagnosis of SARS-CoV-2 (median age, 25 years; interquartile range, 22-31 years; 78% male]. Of these, 590 sailors (80.2%) were characterized as symptomatic, with a median symptom duration of 7 days (interquartile range, 5-11 days) and 146 sailors (19.8%) remained asymptomatic for the duration of the study period. With regard to clinical outcomes, 729 sailors remained in outpatient isolation, 6 were hospitalized, and 1 (a “senior listed member in his 40s”) died during the study period.
Lui GC, Yip TC, Wong VW, et al. Significantly Lower Case-fatality Ratio of Coronavirus Disease 2019 (COVID-19) than Severe Acute Respiratory Syndrome (SARS) in Hong Kong – A Territory-Wide Cohort Study. Clin Infect Dis. 2020 Oct 1:ciaa1187. PubMed: https://pubmed.gov/33005933. Full-text: https://doi.org/10.1093/cid/ciaa1187
Among a cohort of the first 1013 COVID-19 patients (mean age, 38.4 years; 53.9% male) diagnosed from 23 January to 14 April 2020 in Hong Kong, the CFR was 0.4%, and 5% had ICU admission or death within 30 days of hospital admission. Age and diabetes were associated with worse outcomes, whereas antiviral treatments were not.
Clark KEN, Nevin WD, Mahungu T, Lachmann H, Singh A. Assessment of the Haemophagocytic lymphohistiocytosis HScore in patients with COVID-19. Clin Infect Dis. 2020 Sep 28:ciaa1463. PubMed: https://pubmed.gov/32985664. Full-text: https://doi.org/10.1093/cid/ciaa1463
Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome characterized by hypercytokinemia with multiorgan failure. Given the parallel in cytokine profile between HLH and COVID-19, it has been suggested that utilizing the HScore may help identify those patients with the most severe disease, and heightened inflammatory state, who may be more likely to benefit from immunosuppression. In this cohort, the HScore didn’t work. The score did not identify those patients with COVID-19 most at risk of requiring higher levels of care, or at risk of deterioration and death.
Dowd JB, Rotondi V, Mills MC. Dangerous to claim “no clear association” between intergenerational relationships and COVID-19. PNAS September 29, 2020. Full-text: https://doi.org/10.1073/pnas.2016831117
Do intergenerational relationships (e.g., co-residence and contacts between family members of different generations) play a major role in the spread and lethality of COVID-19? A previous study from Italy (where case fatality rate was very high earlier this year) found no clear association. The authors doubt this to be the case. It remains crucial to be mindful of risks to older adults physically interacting with younger relatives.
Kabarriti R, Brodin P, Maron MI. Association of Race and Ethnicity With Comorbidities and Survival Among Patients With COVID-19 at an Urban Medical Center in New York. JAMA Netw Open September 25, 2020;3(9):e2019795. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.19795
Important finding: In this cohort study of 5,902 COVID-19 patients treated at a single academic medical center in New York, survival outcomes of non-Hispanic Black and Hispanic patients were at least as good as those of their non-Hispanic White counterparts when controlling for age, sex, and comorbidities. This is critical to further understanding the observed population differences in mortality by race/ethnicity reported elsewhere, ie it’s a question of access to care?.
El Moheb M, Naar L, Christensen MA, et al. Gastrointestinal Complications in Critically Ill Patients With and Without COVID-19. JAMA September 24, 2020. Full-text: https://doi.org/10.1001/jama.2020.19400
In their research letter, Mohamad El Moheb and colleagues compared the incidence of gastrointestinal complications of 92 critically ill patients with COVID-19–induced acute respiratory distress syndrome (ARDS) vs 92 comparably ill patients with non–COVID-19 ARDS using propensity score analysis. Patients with COVID-19 were more likely to develop gastrointestinal complications (74% vs 37%; P < 0.001). Specifically, patients with COVID-19 developed more transaminitis (55% vs 27%), severe ileus (48% vs 22%), and bowel ischemia (4% vs 0%). High expression of ACE 2 receptors along the epithelial lining of the gut that act as host-cell receptors for SARS-CoV-2 could explain this.
Thapa SB, Kakar TS, Mayer C, et al. Clinical Outcomes of In-Hospital Cardiac Arrest in COVID-19. JAMA Intern Med. Published online September 28, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.4796
Shrinjaya Thapa and colleagues from William Beaumont Hospital in Michigan deserve the award for the most sincere results of the day. Among 1,309 patients hospitalized with COVID-19, 60 (4.6%) developed in-hospital cardiac arrest (IHCA) and underwent CPR. Among 54 patients with CPR documentation, the initial rhythm was non-shockable for 52 patients (96.3%), with 44 with pulseless electrical activity and 8 with asystole. Return of spontaneous circulation (ROSC) was achieved in 29 patients (53.7%). Now guess how many patients of these 54 patients survived? 10? 5? Wrong. The number was zero. There was a 100% mortality rate following CPR. According to the authors, these outcomes “warrant further investigation into the risks and benefits of performing prolonged CPR in this subset of patients, especially because the resuscitation process generates aerosols that may place health care personnel at a higher risk of contracting the virus”. This devastating result is likely driven by several factors, including critical illness and non-shockable initial rhythms. Additionally, presumed respiratory etiology of arrest for most patients, lack of effective treatments and potential delays in response time for donning of personal protective equipment may have contributed.
Schultze A,Walker AJ, MacKenna B, et al. Risk of COVID-19-related death among patients with chronic obstructive pulmonary disease or asthma prescribed inhaled corticosteroids: an observational cohort study using the OpenSAFELY platform. Lancet Respir Med 2020, published 24 September. Full-text: https://doi.org/10.1016/S2213-2600(20)30415-X
There has been speculation that inhaled corticosteroids (ICSs) might protect against infection with SARS-CoV-2 or the development of severe COVID-19. Now Ben Goldacre, Anna Schultze and colleagues show that regular ICS use does not seem to protect against COVID-19-related death among people with asthma or COPD.
Muñoz-Price LS, Nattinger AB, Rivera F, et al. Racial Disparities in Incidence and Outcomes Among Patients With COVID-19. JAMA Netw Open 2020, published 25 September. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.21892
A total of 2595 patients: 785 (30.2%) African-American individuals, 1617 (62.3%) White individuals, and 193 (7.4%) of other racial groups. Silvia Muñoz-Price et al. show that in the first weeks of the COVID-19 pandemic in Milwaukee, Wisconsin, Black race was associated with a positive COVID-19 test and a subsequent need for hospitalization, but only poverty was associated with intensive care unit admission.
Kabarriti R, Brodin P, Maron MI, et al. Association of Race and Ethnicity With Comorbidities and Survival Among Patients With COVID-19 at an Urban Medical Center in New York. JAMA Netw Open 2020, published 25 September. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.19795
Similar results as the previous study: Andrew Racine, Rafi Kabarriti and colleagues report 5902 SARS-CoV-2 positive patients treated at a single academic medical center in New York. While non-Hispanic Black and Hispanic patients had a higher proportion of more than 2 medical comorbidities, their survival outcomes were at least as good as those of their non-Hispanic White counterparts when controlling for age, sex, and comorbidities.
Buitrago-Garcia D, Egli-Gany D, Counotte MJ, et al. Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis. PLOS September 22, 2020. Full-text: https://doi.org/10.1371/journal.pmed.1003346
Diana Buitrago-Garcia and colleagues did a living systematic review through June 10, 2020. Overall, in 79 studies in a range of different settings, 20% (95% CI 17%–25%) of people with SARS-CoV-2 infection remained asymptomatic during follow-up, but biases in study designs limit the certainty of this estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%–37%) remained asymptomatic. There was some evidence that SARS-CoV-2 infection is less likely in contacts of people with asymptomatic infection.
Hughes MM, Groenewold MR, Lessem SE, et al. Update: Characteristics of Health Care Personnel with COVID-19 – United States, February 12-July 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Sep 25;69(38):1364-1368. PubMed: https://pubmed.gov/32970661 . Full-text: https://doi.org/10.15585/mmwr.mm6938a3
This update describes demographic characteristics, underlying medical conditions, hospitalizations, and intensive care unit (ICU) admissions, stratified by vital status, among 100,570 health care providers (HCP) (median age 41 years, 79% females) with COVID-19 reported to CDC during February 12–July 16, 2020. Of persons with known hospitalization status, 8% (6,832 of 83,202) were hospitalized and 5% (1,684 of 33,694) were treated in an ICU. Vital status was known for 67% (67,746) of HCP with COVID-19; among those, 641 (1%) died. HCP with COVID-19 who died tended to be older, male, Asian, Black, and have an underlying medical condition when compared to HCP who did not die. Nursing and residential care facilities were the most commonly reported job setting and nursing the most common single occupation type of HCP with COVID-19.
Pereyra D, Heber S, Jilma B, Zoufaly A, Assinger A. Routine haematological parameters in COVID-19 prognosis. The Lancet Hematology, 7, ISSUE 10, e709, October 01, 2020.
A “negative” study is sometimes valuable: After hundreds of studies emphasizing the prognostic values of clinical and laboratory chemical parameters in hospitalized COVID-19 patients, it’s important to hear that it’s not that easy (at least in Austria). David Pereyra and colleagues analyzed data from 210 consecutive hospitalized patients with COVID-19. In this cohort, hematological parameters such as thrombocytes, neutrophil-to-lymphocyte ratio or D-dimers did not allow prediction of patient outcome. These routine parameters, despite giving guidance on the overall health of the patient, might not always accurately indicate COVID-19-related complications.
Rubin R. As Their Numbers Grow, COVID-19 “Long Haulers” Stump Experts. JAMA September 23, 2020. Full-text: https://doi.org/10.1001/jama.2020.17709
In this nice perspective Rita Rubin summarizes current knowledge on people who still haven’t fully recovered from COVID-19 weeks or even months after symptoms first arose. Fatigue appears to be the most common symptom, followed by muscle or body aches, shortness of breath or difficulty breathing, and difficulty concentrating.
Garibaldi BT, Fiksel J, Muschelli J, et al. Patient Trajectories Among Persons Hospitalized for COVID-19. A Cohort Study. Ann Intern Med, 22 September 2020. Full-text: https://doi.org/10.7326/M20-3905
Of 787 patients admitted with mild-to-moderate disease between March 4 and April 24 in five US hospitals in Maryland and Washington, 302 (38%) progressed to severe disease or death: 181 (60%) by day 2 and 238 (79%) by day 4. Patients had markedly different probabilities of disease progression on the basis of age, nursing home residence, comorbid conditions, obesity, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, hypoalbuminemia, troponin level, and C-reactive protein level and the interactions among these factors. Using only factors present on admission, a model to predict in-hospital disease progression had an area under the curve of 0.85, 0.79, and 0.79, at day 2, 4, and 7, respectively. An interactive version of a so called “COVID-19 Inpatient Risk Calculator” (CIRC) is available at https://rsconnect.biostat.jhsph.edu/covid_predict/.
Foy BH, Carlson JC, Reinertsen E, et al. Association of Red Blood Cell Distribution Width With Mortality Risk in Hospitalized Adults With SARS-CoV-2 Infection. JAMA Netw Open September 23, 2020;3(9):e2022058. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.22058
Red blood cell distribution width (RDW) as a non-specific marker of illness? RDW is a component of complete blood counts that quantifies the variation of individual red blood cell (RBC) volumes and has been shown to be associated with elevated risk for morbidity and mortality in a wide range of diseases. In this large cohort study including 1641 adults diagnosed with SARS-CoV-2 infection and admitted to 4 hospitals in Boston, RDW was associated with mortality risk in Cox models (hazard ratio of 1.09 per 0.5% RDW increase and 2.01 for an RDW > 14.5% vs ≤ 14.5%).
Roncon L, Zuin M, Barco S, et al. Incidence of acute pulmonary embolism in COVID-19 patients: Systematic review and meta-analysis. Eur J Intern Med. 2020 Sep 17:S0953-6205(20)30349-6. PubMed: https://pubmed.gov/32958372. Full-text: https://doi.org/10.1016/j.ejim.2020.09.006
Loris Roncon and colleagues from Rovigo, Italy have analyzed data from 23 studies, including 7178 COVID-19 patients. Among patients hospitalized in general wards and intensive care units (ICU), the pooled in-hospital incidence of pulmonary embolism (PE) or lung thrombosis was 14.7% and 23.4%, respectively. Segmental/sub-segmental pulmonary arteries were more frequently involved compared to main/lobar arteries. (6.8% vs18.8%, p < 0.001). Computer tomography pulmonary angiogram (CTPA) was used in only 35%, suggesting a potential underestimation of PE cases.
Miller J, Fadel RA, Tang A, et al. The Impact of Sociodemographic Factors, Comorbidities and Physiologic Response on 30-day Mortality in COVID-19 Patients in Metropolitan Detroit. Clin Infect Dis. 2020 Sep 18:ciaa1420. PubMed: https://pubmed.gov/32945856. Full-text: https://doi.org/10.1093/cid/ciaa1420
In this large cohort of 3633 COVID-19 patients, those with comorbidities, advanced age, and physiological abnormalities on presentation had higher odds of death. Of note, disparities in income or source of health insurance were not associated with outcomes.
Neilan AM, Losina E, Bangs AC, et al. Clinical Impact, Costs, and Cost-Effectiveness of Expanded SARS-CoV-2 Testing in Massachusetts. Clin Infect Dis. 2020 Sep 18:ciaa1418. PubMed: https://pubmed.gov/32945845. Full-text: https://doi.org/10.1093/cid/ciaa1418
Anne M. Neilan and colleagues projected the clinical and economic impact of alternative testing strategies on COVID-19 incidence and mortality in Massachusetts using a microsimulation model. Four testing strategies were compared: 1) PCR testing only for patients with severe or critical symptoms warranting hospitalization; 2) PCR for any COVID-19-consistent symptoms (symptomatic), with self-isolation if positive; 3) Symptomatic and one-time PCR for the entire population; and, 4) Symptomatic with monthly re-testing for the entire population. Testing people with any COVID-19-consistent symptoms would be cost-saving compared to testing only those whose symptoms warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Despite modest sensitivity, low-cost, repeat screening of the entire population could be cost-effective in all epidemic settings.
Marinho PM, Nascimento H, Marcos AAA, Romano AC, Belfort R Jr. Seeking clarity on retinal findings in patients with COVID-19 – Authors’ reply. Lancet. 2020 Sep 19;396(10254):e40. Full-text: https://doi.org/10.1016/S0140-6736(20)31912-7
Paula M. Marinho and colleagues reply to major concerns (5 letters) that their initial reports on retinal findings in COVID-19 patients (hyper-reflective lesions at the level of the ganglion cell and inner plexiform layers) were, in fact, cuts through normal retinal blood vessels. To ensure that this was not the case, the authors have excluded vertical optical coherence tomography (OCT) scans and used only horizontal scans to avoid vessel crossings. Since their initial report, they have also examined more than 150 patients, demonstrating an absence of blood flow within the retinal lesions of “many” patients, differentiating these lesions from blood vessels with active blood flow.
Westblade LF, Brar G, Pinheiro LC, et al. SARS-CoV-2. Viral Load Predicts Mortality in Patients with and Without Cancer Who Are Hospitalized with COVID-19. Cancer Cell 2020, published 15 September. Full-text: https://doi.org/10.1016/j.ccell.2020.09.007.
The predictive value of viral load? The authors measured SARS-CoV-2 viral load in nasopharyngeal swab specimens of 100 patients with cancer and 2914 without cancer who were admitted to three New York City hospitals. Overall, the in-hospital mortality rate was 38.8% among patients with a high viral load, 24.1% among patients with a medium viral load, and 15.3% among patients with a low viral load (p < 0.001). Similar findings were observed in patients with cancer. The authors also found that patients with hematologic malignancies had higher median viral loads than patients without cancer. They conclude that viral load measurements might be a valuable tool for clinicians in the care of hospitalized patients with COVID-19.
White-Dzuro G, Gibson LE, Zazzeron L, et al. Multisystem effects of COVID-19: A concise review for practitioners. Postgrad Med. 2020 Sep 14. PubMed: https://pubmed.gov/32921198. Full-text: https://doi.org/10.1080/00325481.2020.1823094
The authors review the multi-system complications of COVID-19 and treatment strategies to improve the care of critically ill COVID-19 patients. They stress that clinicians should be aware of the multi-system impact of the disease so that care can be focused on the prevention of end-organ injuries to potentially improve clinical outcomes.
Lee SW, Yang JM, Moon SY, et al. Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: a nationwide cohort study. Lancet Psychiatry 2020, published 17 September. Full-text: https://doi.org/10.1016/S2215-0366(20)30421-1
People with a pre-existing diagnosis of a mental illness are not at increased risk of infection with SARS-CoV-2. This is the result of a large-scale cohort study with propensity score matching using a South Korean national health insurance claims database. Among the patients who tested positive for SARS-CoV-2, after propensity score matching, 109 (8·3%) of 1320 patients without a mental illness had severe clinical outcomes of COVID-19 compared with 128 (9·7%) of 1320 with a mental illness (adjusted OR 1·27, 95% CI 1·01–1·66).
Bixler D, Miller AD, Mattison CP, et al. SARS-CoV-2–Associated Deaths Among Persons Aged <21 Years — United States, February 12–July 31, 2020. MMWR Morb Mortal Wkly Rep. ePub: 15 September 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6937e4
SARS-CoV-2 infection is usually mild in children. Who are those who die nonetheless? Danae Bixler et al. analyzed 121 SARS-CoV-2–associated deaths among persons aged < 21 years. 12 (10%) were infants and 85 (70%) were aged 10–20 years. Hispanic, non-Hispanic Black and non-Hispanic American Indian/Alaskan Native persons accounted for 94 (78%) of these deaths. They conclude that (1) all persons aged < 21 years exposed to SARS-CoV-2 should be monitored for complications and that (2) infants, children, adolescents, and young adults, particularly those from racial and ethnic minority groups at higher risk, those with underlying medical conditions, and their caregivers, need clear, consistent, and developmentally, linguistically, and culturally appropriate COVID-19 prevention messages (e.g., related to mask wearing, physical distancing, hand hygiene).
Kiang MV, Irizarry RA, Buckee CO, et al. Every Body Counts: Measuring Mortality From the COVID-19 Pandemic. Ann Int Med, September 11, 2020. Full-text: https://doi.org/10.7326/M20-3100
This brilliant article discusses the current difficulties of disaster death attribution and describes the strengths and limitations of relying on death counts from death certificates, estimations of indirect deaths, and estimations of excess mortality.
Muscatello DJ, McIntyre PB. Comparing mortalities of the first wave of coronavirus disease 2019 (COVID-19) and of the 1918–19 winter pandemic influenza wave in the USA. International Journal of Epidemiology, 15 September 2020, dyaa186. Full-text: https://doi.org/10.1093/ije/dyaa186
David J Muscatello and Peter B McIntyre used indirect age standardization to calculate standardized mortality ratios (SMRs) for the 1918–19 winter influenza pandemic wave, with the reference mortality rate being COVID-19 death rates for New York City. They also used mortality data for the 2009 pandemic and the severe 2017–18 season as comparators. All-age COVID-19 mortality rates remain substantially lower than those documented in the 1918–19 influenza pandemic, recognizing that 1918–19 mortality was inflated by lack of now routine treatments. The age-adjusted, all-age mortality rate for the 1918–19 winter wave of the influenza pandemic was 6.7 times higher than COVID-19 cumulative mortality rates to 2 June 2020. In < 45-year-olds, the SMR was 42 times higher for influenza in 1918–19 than for COVID in 2020. However, in ≥ 45-year-olds, the SMR was 44% lower in 1918–19 than for COVID in 2020. COVID-19 mortality was more than 10-fold higher than a severe influenza season, and more than 300-fold higher than the 2009–10 influenza pandemic.
Marshall M. The lasting misery of coronavirus long-haulers. Nature September 14, 2020, 585, 339-341. Full-text: https://www.nature.com/articles/d41586-020-02598-6
Doctors are now concerned that the pandemic will lead to a significant surge of people battling lasting illnesses and disabilities. Because the disease is so new, no one knows yet what the long-term impacts will be. This article gives some insights on how some people are still battling crushing fatigue, lung damage and other symptoms of ‘long COVID’, several months after acute illness.
Zong Y, Gu Y, Yu H, et al. Thrombocytopenia Is Associated with COVID-19 Severity and Outcome: An Updated Meta-Analysis of 5637 Patients with Multiple Outcomes. Laboratory Medicine, 15 September 2020, lmaa067. Full-text: https://doi.org/10.1093/labmed/lmaa067
A meta-analysis of 24 studies, showing a weighted incidence of thrombocytopenia in COVID-19 patients of 12.4% (95% CI 7.9%–17.7%). The meta-analysis of binary outcomes (with and without thrombocytopenia) indicated the association between thrombocytopenia and a 3-fold enhanced risk of a composite outcome of intensive care unit admission, progression to acute respiratory distress syndrome, and mortality (odds ratio 3.49; 95% CI, 1.57–7.78).
De Souza L, Nwanji V, Kaur G. An auspicious triumph of recovery from dialysis-requiring acute kidney injury in COVID-19 in a patient with chronic kidney disease, α-1 antitrypsin deficiency, and liver transplant: A case report. Clin Nephrol. 2020 Sep 10. PubMed: https://pubmed.gov/32909541. Full-text: https://doi.org/10.5414/CN110294
Never give up. Luisa De Souza and colleagues report a unique case of an immunosuppressed 67-year-old female with A1AT deficiency and liver transplant with baseline chronic kidney disease (CKD) stage IIIa, recovering from COVID-19 mediated hypoxic respiratory failure complicated by AKI requiring provisional renal replacement therapy.
Crameri GAG, Bielecki M, Züst R, et al. Reduced maximal aerobic capacity after COVID-19 in young adult recruits, Switzerland, May 2020. Euro Surveill. 2020;25(36):pii=2001542. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.36.2001542
Take a cohort of young, predominantly male military recruits (173 men, 26 women) with a median age of 21 years and compare a fitness test after a diagnosis of SARS-CoV-2 infection (median: 45 days; range: 31–58 days) with a baseline test performed 3 months before the infection. What did Jeremy Werner Deuel, Giovanni Crameri and colleagues find? A decrease in maximal aerobic capacity (VO2 max) among COVID-19 convalescent but not among asymptomatic and not-infected recruits. Ca 19% of COVID-19 convalescent recruits showed a decrease of VO2 max of more than 10% as compared with baseline before infection. Never stop following your patients.
Rajpal S, Tong MS, Borchers J, et al. Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection. JAMA Cardiol. Published online September 11, 2020. Full-text: https://doi.org/10.1001/jamacardio.2020.4916
Recent studies have raised concerns of myocardial inflammation after recovery from COVID-19, even in asymptomatic or mildly symptomatic patients. Here, Saurabh Rajpal et al. performed a comprehensive cardiac magnetic resonance (CMR) examination including cine, T1 and T2 mapping, extracellular volume fraction, and late gadolinium enhancement (LGE), on a 1.5-T scanner in 26 SARS-CoV-2 infected competitive athletes. Four of them (15%) had CMR findings suggestive of myocarditis and 8 additional athletes (30.8%) exhibited LGE without T2 elevation suggestive of prior myocardial injury. Long-term follow-up is required to understand CMR changes in competitive athletes.
Meizlish ML, Pine AB, Bishai JD. A neutrophil activation signature predicts critical illness and mortality in COVID-19. medRxiv 2020, posted 2 September. Full-text: https://doi.org/10.1101/2020.09.01.20183897
In this pre-published article, Hyung Chun, Alfred Lee, Matthew Meizlish and colleagues carried out proteomic profiling of plasma and analyzed clinical data from over 3,300 patients. Their findings suggest that increased circulating levels of neutrophil activators (G-CSF, IL-8) and neutrophil effectors (RETN, LCN2, HGF, and MMP8) might identify non-critically ill patients who are at risk of becoming critically ill. Attention: this article has not yet been peer reviewed!
Cunningham JW, Vaduganathan M, Claggett BL, et al. Clinical Outcomes in Young US Adults Hospitalized With COVID-19. JAMA Intern Med 2020, published 9 September. Full-text: https://doi.org/10.1001/jamainternmed.2020.5313
Does COVID-19 spare young people? Of course not. Here is the proof by Scott Solomon, Jonathan Cunningham and colleagues. They investigated the outcomes of 3222 young adults (age 18 to 34 years) hospitalized for COVID-19. 684 patients (21%) required intensive care, 331 (10%) mechanical ventilation, and 88 patients (2.7%) died. Morbid obesity and hypertension were associated with a greater risk of death or mechanical ventilation. Importantly, young adults age 18 to 34 years with multiple risk factors (morbid obesity, hypertension, and diabetes) faced risks similar to 8862 middle-aged (age 35-64 years) adults without these conditions.
See also the short comment by Katz MH. Regardless of Age, Obesity and Hypertension Increase Risks With COVID-19. JAMA Intern Med 2020, published 9 September. Full-text: https://doi.org/10.1001/jamainternmed.2020.5415 and
Rhee C, Baker M, Vaidya V, et al. Incidence of Nosocomial COVID-19 in Patients Hospitalized at a Large US Academic Medical Center. JAMA Netw Open. 2020;3(9):e2020498. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.20498
How adequate are COVID-19 infection control practices in acute care hospitals? Look at nosocomial transmission of SARS-CoV-2! Here, Chanu Rhee et al. analyzed 9149 patients admitted to a large academic medical center, 697 of whom tested positive for SARS-CoV-2 infection. Of these, only 1 case was deemed to be hospital-acquired, most likely from a pre-symptomatic spouse who was visiting daily and diagnosed with COVID-19 before visitor restrictions and masking were implemented. The authors conclude that nosocomial COVID-19 was rare even during the height of the pandemic. At least at Brigham and Women’s Hospital, Boston, USA.
Fernandes Valente Takeda C, Moura de Almeida M, Gonçalves de Aguiar Gomes R, et al. Case Report: Recurrent Clinical Symptoms of COVID-19 in Healthcare Professionals: A Series of Cases from Brazil. Am J Trop Med Hyg. 2020 Sep 4. PubMed: https://pubmed.gov/32888288. Full-text: https://doi.org/10.4269/ajtmh.20-0893
Luciano Pamplona de Góes Cavalcanti, Christianne Fernandes Valente Takeda and colleagues describe six cases of recurrent SARS-CoV-2 infection in Brazilian healthcare professionals. The time elapsed between the onset of symptoms in the two episodes ranged from 53 to 70 days. Most recurrences progressed without complications. Unfortunately, sequencing of the virus was not possible.
Blackburn J, Yiannoutsos CT, Carroll AE, Halverson PK, Menachemi N. Infection Fatality Ratios for COVID-19 Among Noninstitutionalized Persons 12 and Older: Results of a Random-Sample Prevalence Study. Ann Intern Med. 2020 Sep 2. PubMed: https://pubmed.gov/32877214. Full-text: https://doi.org/10.7326/M20-5352
This study combines prevalence estimates from a state-wide random sample with Indiana (US) vital statistics data of confirmed COVID-19 deaths. The overall non-institutionalized IFR in the state was remarkably low: 0.26%. The demographic-stratified IFR varied most by age, race, ethnicity, and sex. Persons younger than 40 years had an IFR of 0.01%; those aged 60 or older had an IFR of 1.71%. Whites had an IFR of 0.18%; non-Whites had an IFR of 0.59%.
Quast T, Andel R, Gregory S, Storch EA. Years of life lost associated with COVID-19 deaths in the United States. Journal of Public Health, 07 September 2020, fdaa159. Full-text: https://doi.org/10.1093/pubmed/fdaa159
Years of life lost (YLL) estimates the number of years that those who died would have lived if they had not contracted the specified condition. This study of roughly the first 5 months of the COVID-19 epidemic in the USA, calculating the YLLs by jurisdiction and gender, estimates 1.2 million YLLs due to COVID-19.
Sax P. An ID Doctor’s Confrontation with His Own Case of COVID-19 – An Interview with Dr. Michael Saag. Open Forum Infectious Diseases 04 September 2020, Volume 7, Issue 9, 1 September 2020. Full-text: https://doi.org/10.1093/ofid/ofaa395
Read how Michael Saag, a well-known HIV researcher from the University of Alabama, Birmingham, was confronted with his own infection, after picking up the virus from his son. Read about his thoughts on the evening of the sixth day, when the cytokine storm started. And how he spent the following 8 days and nights, watching his pulse race like a hawk and knowing that in the next 15 minutes, it might drop below 90 and he would end up in the hospital. Also available as a podcast.
Yelin D, Wirtheim E, Vetter P, et al. Long-term consequences of COVID-19: research needs. Lancet Inf Dis September 01, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30701-5
Weeks and months after the onset of acute COVID-19, people continue to suffer. But how many? In their important comment on the trajectory of people recovering from COVID-19, Dana Yelin addresses the key issues. A clear definition of patient inclusion criteria, a common protocol, and uniform definitions of outcomes and ways to measure them are required.
Buetti N, Patrier J, Le Hingrat Q, et al. Risk factors for SARS-CoV-2 detection in blood of critically ill patients. Clinical Infectious Diseases, 02 September 2020. Full-text: https://doi.org/10.1093/cid/ciaa1315
Of 81 blood samples for SARS-CoV-2 detection (from 42 critically ill patients), 30 (37%) were positive. Immunosuppression (OR 12.16, 95% CI 1.74-84.93, p = 0.013) and chronic renal failure (OR 5.98) increased the risk for SARS-CoV-2 detection in the blood. In contrast to previous reports, SARS-CoV-2 detection in the blood was not associated with 6-week mortality.
Boulle A, Davies MA, Hussey H, et al. Risk factors for COVID-19 death in a population cohort study from the Western Cape Province, South Africa. Clin Infect Dis. 2020 Aug 29:ciaa1198. PubMed: https://pubmed.gov/32860699. Full-text: https://doi.org/10.1093/cid/ciaa1198
The by far longest co-author list of the day. Around 300 researchers were needed to evaluate risk factors among 3,460,932 patients (16% HIV+) in South Africa. In total, 22,308 were diagnosed with COVID-19, of whom 625 died. COVID-19 death was associated with male sex, increasing age, diabetes, hypertension and chronic kidney disease. HIV and current tuberculosis were independently associated with increased COVID-19 mortality. Adjusted hazard ratio for mortality was 2.14 for HIV (95% CI 1.70-2.70), with similar risks across strata of viral load and immunosuppression. Current and previous tuberculosis were also associated with COVID-19 death (aHRs 2.70 and 1.51).
White PL, Dhillon R, Cordey A, et al. A national strategy to diagnose COVID-19 associated invasive fungal disease in the ICU. Clin Infect Dis. 2020 Aug 29:ciaa1298. PubMed: https://pubmed.gov/32860682. Full-text: https://doi.org/10.1093/cid/ciaa1298
P Lewis White and colleagues from Wales have screened 135 patients admitted to Welsh ICUs with COVID-19 infection for invasive fungal co-infection. The incidence was 26.7% (14.1% aspergillosis, 12.6% yeast infections). The overall mortality rate was 53% and 31% in patients with and without fungal disease, respectively. The use of corticosteroids and history of chronic respiratory disease increased the likelihood of aspergillosis. The authors conclude that screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.
Jones E. The psychology of protecting the UK public against external threat: COVID-19 and the Blitz compared. Lancet Psychiatry 2020, published 27 August. Full-text: https://doi.org/10.1016/S2215-0366(20)30342-4
Do the SARS-CoV-2 pandemic and the German World War 2 aerial bombing campaign against the UK (The Blitz) have something in common? Exposure of the civilian population to a sustained threat, leading to a range of protective measures and behavioral regulations? Follow Edgar Jones on this trip through a phoney war, shelter occupation, deep shelter, adaptation to threat, second wave and risk communication. Your Sunday read.
Hagman K, Hedenstierna M, Gille-Johnson P, et al. SARS-CoV-2 RNA in serum as predictor of severe outcome in COVID-19: a retrospective cohort study. Clinical Infectious Diseases, August 28, 2020. Full-text: https://doi.org/10.1093/cid/ciaa1285
SARS-CoV-2 in serum is unfavorable. In this retrospective study of 167 COVID-19 patients who underwent serum PCR analysis at hospital admission, 3 of 106 serum PCR negative patients and 15 of 61 positive patients died. The hazard ratios for critical disease and all-cause mortality were 7.2 (95% CI 3.0-17) and 8.6 (95% CI 2.4-30) for patients with a positive serum PCR.
Pezzini A, Padovani A. Lifting the mask on neurological manifestations of COVID-19. Nat Rev Neurol 2020, published 28 August. Full-text: https://doi.org/10.1038/s41582-020-0398-3
Another review. Alessandro Pezzini and Alessandro Padovani present preclinical research suggesting that SARS-CoV-2 could be responsible for many neurological manifestations, and summarize the biological pathways that could underlie each neurological symptom.
McCarty TR, Hathorn KE, Redd WD, et al. How Do Presenting Symptoms and Outcomes Differ by Race/Ethnicity Among Hospitalized Patients with COVID-19 Infection? Experience in Massachusetts. Clin Infect Dis 2020, published 22 August. Full-text: https://doi.org/10.1093/cid/ciaa1245
Pre-existing societal inequities, many of which are a result of long-standing structural racism, place Black and Latinx communities and individuals at greater risk of being adversely affected by such disasters. But is there an association between race/ethnicity and clinically relevant hospitalization outcomes, including in-hospital mortality? Walter Chan, Thomas McCarthy and colleagues give us a differentiated appraisal in this retrospective analysis of nine Massachusetts hospitals including all consecutive adult patients hospitalized with laboratory-confirmed COVID-19 (n = 379). Latinx patients were younger, had fewer cardiopulmonary disorders, were more likely to be obese, more frequently reported fever and myalgia, and had lower D-dimer levels compared to white patients (p < 0.05). However, after controlling for confounders (age, gender, obesity, cardiopulmonary comorbidities, hypertension, and diabetes), no significant differences in in-hospital mortality, ICU admission, or mechanical ventilation by race/ethnicity were found. In other words, despite a disproportionate infection rate among Black and Latinx individuals, when their disease is severe enough to require hospitalization, these patients do just as well in terms of important outcomes, including mortality.
Stefanini GG, Chiarito M, Ferrante G, et al. Early detection of elevated cardiac biomarkers to optimise risk stratification in patients with COVID-19. Heart. 2020 Aug 14:heartjnl-2020-317322. PubMed: https://pubmed.gov/32817312. Full-text: https://doi.org/10.1136/heartjnl-2020-317322
An early risk stratification is crucial in order to identify the patients that might benefit from intense monitoring and aggressive treatment strategies. Here Giulio Stefanini et al. stratify 397 patients according to elevated levels of high-sensitivity cardiac troponin I (hs-TnI, a biomarker of myocardial injury), B-type natriuretic peptide (BNP, a biomarker of cardiac stress) or both measured within 24 hours after hospital admission. The rate of mortality was higher in patients with elevated hs-TnI (22.5%), BNP (33.9%) or both (55.6%) as compared with those without elevated cardiac biomarkers (6.25%). The authors recommend cardiac biomarkers to be systematically assessed in patients with COVID-19 at the time of hospital admission.
Nachtigall I, Lenga P, Jóźwiak K, et al. Clinical course and factors associated with outcomes among 1904 patients hospitalized with COVID-19 in Germany: an observational study. Clin Microbiol Infect 2020, published 18 August. Full-text: https://doi.org/10.1016/j.cmi.2020.08.011
In Germany, the COVID-19 pandemic has been associated with a lower case fatality rate (CFR) compared with other Western and Central European countries. The reason? Age! During the first COVID-19 wave in spring 2020, the median age of SARS-CoV-2 infected people in Germany was much lower than in Italy, for example. As younger people have a more benign clinical course, the German CFR remained low. However, once German patients with COVID-19 were admitted to an intensive care unit (ICU), the mortality rate was 29% and thus comparable to other European countries. This is the result of a retrospective cohort study of 1904 patients (median age: 73 years) admitted to a national network of German hospitals, by Irit Nachtigall, Julius Dengler and colleagues. As expected, the authors also find that the most prominent risk factors for death are male sex, pre-existing lung disease, and increased patient age. The mortality rates in detail:
Yueh B. The Worst Patient—A Physician With COVID-19. JAMA Otolaryngol Head Neck Surg 2020, published 20 August. Full-text: https://doi.org/10.1001/jamaoto.2020.2435
As an accomplished surgeon who has missed fewer than 2 weeks of work in 30 years, proud that you operated 2 weeks later with a broken leg and ankle ski lift accident, how could you possibly accept to miss week after week with COVID-19? Bevan Yueh had a hard time. Read about denial, whistleblowers, 500 cc spirometry and nightmares!
Tucker NR, Chaffin M, Bedi KC Jr, et al. Myocyte-Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2-Mediated Myocarditis. Circulation. 2020 Aug 18;142(7):708-710. PubMed: https://pubmed.gov/32795091 . Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047911
Nathan Tucker and colleagues assessed ACE2 expression by performing bulk and single nucleus RNA-Seq on the left ventricles of 11 individuals with dilated cardiomyopathy, 15 individuals with hypertrophic cardiomyopathy, and 16 controls with non-failing hearts. Data suggest that previous cardiovascular disease is a predominant driver of cardiomyocyte-specific increased transcription of ACE2, providing a pathologic link for SARS-CoV–associated viral myocarditis.
Yehia BR, Winegar A, Fogel R, et al. Association of Race With Mortality Among Patients Hospitalized With Coronavirus Disease 2019 (COVID-19) at 92 US Hospitals. JAMA Netw Open. 2020;3(8):e2018039. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.18039
In this cohort study of 11,210 individuals with COVID-19 presenting for care at 92 hospitals across 12 states, there was no difference in all-cause, in-hospital mortality between white and black patients after adjusting for age, sex, insurance status, comorbidity, neighborhood economics, and site of care.
Wu F, Liu M, Wang A, et al. Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China. JAMA Intern Med August 18, 2020. Full-text: https//doi.org/10.1001/jamainternmed.2020.4616
In this cohort study of 175 patients who recovered from mild COVID-19, neutralizing antibody titers (NAbs) varied substantially at the time of discharge. NAbs were detected in patients from day 4 to 6 and reached peak levels from day 10 to 15 after disease onset. Of note, there were 10 patients whose NAb titers were less than the detectable level of the assay.
Iadecola C, Anrather J, Kamel H. Effects of COVID-19 on the nervous system. Cell 2020, published 19 August. Full-text: https://www.cell.com/cell/fulltext/S0092-8674(20)31070-9
Many hospitalized COVID-19 patients exhibit neurological manifestations, ranging from headache and loss of smell, to confusion and disabling strokes. The disease might also take a toll on the nervous system in the long term. Follow Costantino Iadecola, Josef Anrather and Hooman Kamel in this appraisal of the potential for neurotropism and mechanisms of neuropathogenesis of SARS-CoV-2.
Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020 Aug 11;370:m3026. PubMed: https://pubmed.gov/32784198. Full-text: https://doi.org/10.1136/bmj.m3026
Up to 10% of people may experience prolonged illness after COVID-19. Trish Greenhalgh and colleagues give a thorough overview of the management of post-acute COVID-19 (“long COVID”). A must-read for all practitioners.
Tatu AL, Nadasdy T, Bujoreanu FC. Familial Clustering of COVID-19 Skin Manifestations. Dermatol Ther. 2020 Aug 14:e14181. PubMed: https://pubmed.gov/32794366. Full-text: https://doi.org/10.1111/dth.14181
Does genetics play a role in the manifestation of viral exanthems? Probably, according to this report of a familial clustering of a maculopapular COVID-19 rash. Among 8 people in a family who contracted SARS-CoV-2 infection, only the 4 who were related by blood presented dermatological manifestations.
Alwan NA. A negative COVID-19 test does not mean recovery. Nature 2020, published 11 August. Full-text: https://www.nature.com/articles/d41586-020-02335-z
Data from a UK smartphone app for tracking symptoms suggests that at least one in ten of those reporting are ill for more than three weeks. Clinicians have an idea of who is at increased risk of dying from COVID, but they don’t know who is more likely to experience prolonged ill health following symptomatic, or even asymptomatic, SARS-CoV-2 infection. Nisreen Alwan insists that we need a new ‘recovery’ definition. That definition must include duration, severity and fluctuation of symptoms, as well as functionality and quality of life. The narrow narrative of death as the only bad outcome from COVID needs broadening to include people becoming less healthy, less capable, less productive and living with more pain.
Uppuluri EM, Shapiro NL. Development of pulmonary embolism in a nonhospitalized patient with COVID-19 who did not receive venous thromboembolism prophylaxis. Am J Health Syst Pharm 2020, published 11 August. Full-text: https://doi.org/10.1093/ajhp/zxaa286
Ellen Uppuluri and Nancy Shapiro report a the case of a 32-year-old, overweight (weight, 90 kg; body mass index, 28) male who was treated for COVID-19 in an emergency department (ED) and discharged home. Twelve days later he was found to have a PE. The authors suggest that non-hospitalized patients with COVID-19 may be at higher risk for VTE than patients with other medical illnesses.
Poletti P, Tirani M, Cereda D, et al. Age-specific SARS-CoV-2 infection fatality ratio and associated risk factors, Italy, February to April 2020. Euro Surveill. 2020 Aug;25(31). PubMed: https://pubmed.gov/32762797. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.31.2001383
Piero Poletti, Marcello Tirani and colleagues analyzed 5,484 close contacts of COVID-19 cases in Italy. Infection fatality ratio was 0.43% for individuals younger than 70 years and 10.5% for older individuals. The risk of death after infection was 62% lower in clusters identified after 16 March 2020 and 1.8-fold higher for males.
Crosby SS. My COVID-19. Ann Intern Med 2020, published 11 August. Full-text: https://www.acpjournals.org/doi/10.7326/M20-5126
In this On Being a Doctor report, Sondra Crosby, working at the center of the Boston coronavirus storm in March 2020, remembers a myriad of symptoms after coming down with COVID-19 herself. Read about her shortness of breath, confusion, not eating for 5 days, keeping in the prone position and a nauseating and horrid odor. With the exception of a handful of mediocre and uninspired politicians, this is not something you would wish on your worst enemy.
Lee S, Kim T, Lee E, et al. Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea. JAMA Intern Med, August 6, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.3862
This cohort study included 303 patients in a community treatment center in the Republic of Korea, among them 110 (36.3%) asymptomatic at the time of isolation (21 developed symptoms during isolation). The cycle threshold values of RT-PCR for SARS-CoV-2 (“viral load”) in asymptomatic patients were similar to those in symptomatic patients. Of note, the Ct values from lower respiratory tract specimens tended to decrease more slowly in asymptomatic patients than in symptomatic (including pre-symptomatic) patients.
Kaige Wang, Jianfei Luo, Fen Tan, Jiasheng Liu, Zhong Ni, Dan Liu, Panwen Tian, Weimin Li, Acute pancreatitis as the initial manifestation in two cases of COVID-19 in Wuhan, China, Open Forum Infectious Diseases, , ofaa324, https://doi.org/10.1093/ofid/ofaa324
Tingting Liao, Zhengrong Yin, Juanjuan Xu, Zhilei Lv, Sufei Wang, Limin Duan, Jinshuo Fan, Yang Jin, The correlation between clinical features and viral RNA shedding in outpatients with COVID-19, Open Forum Infectious Diseases, https://doi.org/10.1093/ofid/ofaa331
Perez-Guzman PN, Daunt A, Mukherjee S, et al. Clinical characteristics and predictors of outcomes of hospitalized patients with COVID-19 in a multi-ethnic London NHS Trust: a retrospective cohort study. Clin Infect Dis 2020, published 7 August. Full-text: https://doi.org/10.1093/cid/ciaa1091
In the UK, ethnic minorities are disproportionately affected by COVID-19. Shevanthi Nayagam and colleagues evaluated the factors associated with mortality in patients admitted for COVID-19 in three large London hospitals. As of 1 May, 381 of 614 patients (62%) were discharged alive, 178 (29%) died and 55 (9%) remained hospitalized. The authors provide evidence that, beyond the widely reported factors associated with increased COVID-19 mortality (age, sex and severe hypoxemia on admission), thrombocytopenia, leukocytosis, hypoalbuminemia and reduced eGFR are also significantly associated with increased in-hospital death. They also find an association of increased odds of death among black (compared to white) patients, when adjusted for age, sex, burden of comorbidities and severity of disease on admission.
Wang K, Luo J, Tan F, et al. Acute pancreatitis as the initial manifestation in two cases of COVID-19 in Wuhan, China. Open Forum Infect Dis 2020, published 7 August. Full-text: https://doi.org/10.1093/ofid/ofaa324
Weimin Li and colleagues describe two cases of COVID-19 (two males, 42 and 35 years old) with acute pancreatitis as the initial manifestation.
A dual-physician couple — a cardiology fellow and a general surgery resident —narrate their experience of memorizing the ARDSNet ladder for ratios of positive end-expiratory pressure and fraction of inspired oxygen instead of learning the ins and outs of coronary angiography and laparoscopy. In the middle of their unexpected experience: their 3½ year-old son and the Zoom session decision to keep him safe.
Pujadas E, Chaudry F, McBride R, et al. SARS-CoV-2 viral load predicts COVID-19 mortality. Lancet Respir Med August 06, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30354-4
In this large cohort (n=1145) of hospitalized, symptomatic patients from New York, viral loads were measured. In a Cox proportional hazards model adjusting for several confounders, Carlos Cordon-Cardo and colleagues found a significant independent association between viral load and mortality (hazard ratio 1.07, 95% CI 1.03–1.11, p = 0.0014), with a 7% increase in hazard for each log transformed copy / mL.
Califf RM, Hernandez AF, Landray M, et al. Weighing the Benefits and Risks of Proliferating Observational Treatment Assessments: Observational cacophony, randomized harmony. JAMA. Published online July 31, 2020. Full-text: https://doi.org/10.1001/jama.2020.13319
The authors provide some thoughts on how hundreds of observational studies that have added nothing more than noise, confusion, and false confidence when their findings were widely disseminated by the lay media.
Zhao J, Yang Y, Huang H, et al. Relationship between the ABO Blood Group and the COVID-19 Susceptibility. Clinical Infectious Diseases, August 4, 2020, ciaa1150, https://doi.org/10.1093/cid/ciaa1150.
Among 3700 patients from Wuhan, the risk for infection significantly increased for blood group A (OR 1.3, 95% CI1.1-1.4) and decreased for blood group O (OR 0.7, 95% CI 0.6-0.8). Blood group O was associated with a lower risk of death compared with non-O groups, with an OR of 0.7 (95% CI 0.5-0.9). On the other hand, blood group A was associated with a higher risk of death compared with non-A groups, with an OR of 1.5 (95% CI 1.1-2.0). However, many open questions remain and the authors conclude that it would be premature to use this study to guide clinical practice at this time.
Anderson MR, Geleris J, Anderson DR, et al. Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection. Ann Intern Med 2020, published 29 July. Full-text: https://www.acpjournals.org/doi/10.7326/M20-3214
Should obesity be associated with increased risk for intubation or death from COVID-19 in adults younger than 65 years, but not in adults aged 65 years or older? That’s the suggestion of a large multi-ethnic cohort study by Michaela Anderson and colleagues who looked at 2466 adults hospitalized with SARS-CoV-2 infection in a quaternary academic medical center and community hospital in New York City. Compared with overweight patients, patients with obesity had higher risk for intubation or death, with the highest risk among those with class 3 obesity (hazard ratio, 1.6 [95% CI, 1.1 to 2.1]). Interestingly, this association was primarily observed among patients who were younger than 65 years, but not in older patients (p for interaction by age = 0.042). Body mass index was not associated with admission levels of biomarkers of inflammation, cardiac injury, or fibrinolysis.
Discover multiple potential mechanisms that may underlie the observed association of obesity with acute respiratory failure and death from SARS-CoV-2 infection.
Karagiannidis C, Mostert C, Hentschker C, et al. Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study. Lancet Respir Med 2020, published 28 July. Full-text: https://doi.org/10.1016/S2213-2600(20)30316-7
In this observational study, Christian Karagiannidis and colleagues report on 10,021 adult patients with a confirmed COVID-19 diagnosis, who were admitted to 920 hospitals in Germany between 26 February and 19 April 2020. The median age was 72 years. 1727 patients (17%) needed mechanical ventilation. The main findings:
- Patients on mechanical ventilation had more comorbidities than patients without mechanical ventilation
- Mortality was 53% in patients being mechanically ventilated, reaching 63% in patients aged 70–79 years and 72% in patients aged 80 years and older
- Mortality was 73% in patients requiring both ventilation and dialysis
|Table 1. Mortality in patients of the German AOK study.|
|With ventilation + dialysis||78%
Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 2020. MMWR Morb Mortal Wkly Rep. ePub: 24 July 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6930e1
What is the clinical course of COVID-19 and how long does it take for persons with milder illness to return to baseline health? Mark W. Tenforde and colleagues provide us with a treasure of data. They conducted telephone interviews with a random sample of adults aged ≥ 18 years who were tested SARS-CoV-2 positive at an outpatient visit at one of 14 US academic health care systems. Interviews were conducted 14 – 21 days after the test date. 274 persons reported one or more symptoms at testing and were included in this analysis. The median age of symptomatic respondents was 42.5 years Overall, 141 of 264 (53%) with available data reported one or more chronic medical conditions. Among the 270 of 274 interviewees with available data on return to usual health, 175 (65%) reported that they returned to their usual state of health a median of 7 days (IQR = 5–12 days) from the date of testing. Ninety-five (35%) reported that they had not returned to their usual state of health at the time of interview. The proportion who had not returned to their usual state of health differed across age groups: 26% of interviewees aged 18 – 34 years, 32% aged 35 – 49 years, and 47% aged ≥ 50 years reported not having returned to their usual state of health (p = 0.010) within 14–21 days after receiving a positive test result.
Mackey K, Kansagara D, Vela K. Update Alert 2: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults. Ann Intern Med. 2020 Jul 23. PubMed: https://pubmed.gov/32701362. Full-text: https://doi.org/10.7326/L20-0969
In this second monthly update of a living review (Medline), inclusion of three new meta-analyses and five new observational studies did not change the certainty of evidence rating reported in the original manuscript: there is high-certainty evidence that ACEI or ARB use is not associated with more severe COVID-19 disease.
Walker A, Potting G, Scott A, Hopkins C. Anosmia and loss of smell in the era of covid-19. BMJ 2020;370:m2808. Full-text: https://doi.org/10.1136/bmj.m2808 (Published 21 July 2020)
The BMJ 10-Minute Consultation summarizes in four points what you need to do:
- Half of patients with COVID-19 may lose their sense of smell; guidance states that a new change or loss in sense of smell should prompt a period of self-isolation
- Nine in 10 patients can expect substantial improvement in their sense of smell within four weeks
- Most patients with loss of smell do not require further investigations or referral, although their COVID-19 status should be established if possible
- Treatment involves reassurance, olfactory training, safety advice, and topical corticosteroids—but oral prednisolone should be avoided where acute COVID-19 infection is suspected
Covid-19: What do we know about “long covid”? BMJ 2020;370:m2815. Full-text: https://doi.org/10.1136/bmj.m2815
A reminder of “long COVID-19”. In particular, re-read Paul Garner’s experience: For 7 weeks I have been through a roller coaster of ill health, extreme emotions, and utter exhaustion. The BMJ Opinion, 5 May 2020. Full-text: https://blogs.bmj.com/bmj/2020/05/05/paul-garner-people-who-have-a-more-protracted-illness-need-help-to-understand-and-cope-with-the-constantly-shifting-bizarre-symptoms/ (accessed 16 May 2020)
Hadjieconomou S, Hughes J. Covid-19 associated chilblain-like lesions in an asymptomatic doctor. BMJ 2020;370:m2245. Full-text. https://doi.org/10.1136/bmj.m2245 (Published 22 July 2020)
A reminder of chilblain with two photos.
Pham TD, Huang CH, Wirz OF, et al. SARS-CoV-2 RNAemia in a Healthy Blood Donor 40 Days After Respiratory Illness Resolution. Ann Int Med Jul 17, 2020. Full-text: https://doi.org/10.7326/L20-0725
What happened here? The authors describe a case of donor RNAemia more than one month after symptom resolution. Plasma viral RNA was reproducibly detected at a time point that exceeded recommendations for deferral based on time since symptom resolution (14 days). Given the low viral load, however, these data suggest that this donor posed a limited but uncertain risk to the safety of the blood supply.
Perez-Saez J, Lauer SA, Kaiser L. Serology-informed estimates of SARS-CoV-2 infection fatality risk in Geneva, Switzerland. Lancet July 14, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30584-3
This important study has estimated age-specific infection fatality risks (IFRs) for Geneva, Switzerland, using population-based seroprevalences. After accounting for demography and age-specific seroprevalence, the population-wide IFR was 0.64% (0.38–0.98). Check your age: IFR differed markedly between the age groups. IFR was only 0.0092% (95% between 0.0042–0.016) for individuals aged 20–49 years, 0.14% (0.096–0.19) for those aged 50–64 years but 5.6% (4.3–7.4) for those aged 65 years and older.
Buscarini E, Manfredi G, Brambilla G, et al. GI symptoms as early signs of COVID-19 in hospitalised Italian patients. Gut. 2020 Aug;69(8):1547-1548. PubMed: https://pubmed.gov/32409587 . Full-text: https://doi.org/10.1136/gutjnl-2020-321434
Among 411 consecutive COVID-19 patients, 42 (10.2%) reported GI symptoms including nausea (4.3%), vomiting (3.8%), diarrhea (3.6%) or abdominal pain (1.2%). GI symptoms had a mean onset of 4.9 ± 4.4 days before admission. Absence of cough was reported in 35/42 (83%) patients with GI symptoms. According to the authors, their findings of these 10% of COVID-19 patients confirms that the prevalence of GI symptoms at onset “is not negligible”. That’s probably why this was published in Gut.
Yadav DK, Singh A, Zhang Q, et al. Involvement of liver in COVID-19: systematic review and meta-analysis. Gut. 2020 Jul 15:gutjnl-2020-322072. PubMed: https://pubmed.gov/32669289. Full-text: https://doi.org/10.1136/gutjnl-2020-322072
In this meta-analysis of 9 studies with a total of 2115 patients, patients with COVID-19 with liver injury were at an increased risk of severity (OR 2.57) and mortality (1.66). Thus, special attention should be given to any liver dysfunction while treating patients with COVID-19.
Belanger MJ, Hill MA, Angelidi AM, Dalamaga M, Sowers JR, Mantzoros CS. Covid-19 and Disparities in Nutrition and Obesity. N Engl J Med. 2020 Jul 15. PubMed: https://pubmed.gov/32668105. Full-text: https://doi.org/10.1056/NEJMp2021264
Nice perspective. Though the factors underlying racial and ethnic disparities in COVID-19 in the United States are multifaceted and complex, long-standing disparities in nutrition and obesity play a crucial role in the health inequities unfolding during the pandemic.
Zhang AJ, Lee AC, Chu H, et al. SARS-CoV-2 infects and damages the mature and immature olfactory sensory neurons of hamsters. Clin Infect Dis. 2020 Jul 15. PubMed: https://pubmed.gov/32667973. Full-text: https://doi.org/10.1093/cid/ciaa99532667967
Poor golden Syrian hamsters. But, this probably explains what happens in your nose. After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues peaking between 2 to 4 days post-infection with the highest viral load detected at day 2 post-infection.
Fauvel C, Weizman O, Trimaille A. Pulmonary embolism in COVID-19 patients: a French multicentre cohort study. European Heart Journal, 13 July 2020. Full-text: https://doi.org/10.1093/eurheartj/ehaa500
In this retrospective multicentre study, 103/1,240 (8.3%) consecutive patients hospitalized for COVID-19 (patients who were directly admitted to an ICU were excluded) had evidence for PE. In a multivariable analysis, male gender, anticoagulation with a prophylactic or therapeutic dose, elevated C-reactive protein, and time from symptom onset to hospitalization were associated with PE risk. PE risk factors in the COVID-19 context do not include traditional thromboembolic risk factors but rather independent clinical and biological findings at admission, including a major contribution of inflammation.
Bäuerle A, Teufel N, Musche V. Increased generalized anxiety, depression and distress during the COVID-19 pandemic: a cross-sectional study in Germany. Journal of Public Health, 13 July 2020. Full-text: https://doi.org/10.1093/pubmed/fdaa106
The more you know, the more afraid you’ll be of COVID-19. In this cross-sectional study on 15,704 German residents, trust in governmental actions to face COVID-19 and the subjective level of information regarding COVID-19 were negatively associated with mental health burden. However, the subjective level of information regarding COVID-19 was positively associated with increased COVID-19-related fear.
Smithgall MC, Dowlatshahi M, Spitalnik SL. Types of Assays for SARS-CoV-2 Testing: A Review Laboratory Medicine, 2020, Jul 13. Full-text: https://doi.org/10.1093/labmed/lmaa039
Comprehensive review of multiple novel assays for SARS-CoV-2 diagnosis, including molecular and serologic-based tests, some with point-of-care testing capabilities.
Shafi AMA, Shaikh SA, Shirke MM, Iddawela S, Harky A. Cardiac manifestations in COVID-19 patients-A systematic review. J Card Surg. 2020 Jul 11. PubMed: https://pubmed.gov/32652713. Full-text: https://doi.org/10.1111/jocs.14808
This literature review includes 61 articles on a wide array of cardiovascular manifestations (including heart failure, cardiogenic shock, arrhythmia, and myocarditis among others) and cardiac-specific biomarkers (including CK-MB, CK, myoglobin, troponin, and NT-proBNP) as prognostic tools. But who did review this review? In the methods, there is no date re: when this analysis was performed.
Naeini AS, Karimi-Galougahi M, Raad N, et al. Paranasal sinuses computed tomography findings in anosmia of COVID-19. Am J Otolaryngol. 2020 Jul 3;41(6):102636. PubMed: https://pubmed.gov/32652405. Full-text: https://doi.org/10.1016/j.amjoto.2020.102636
Interesting finding: among 49 confirmed COVID-19 patients with anosmia, there were no significant pathological changes in the paranasal sinuses on CT scans. Olfactory cleft and ethmoid sinuses appeared normal while in other sinuses, partial opacification was detected only in some cases. Conductive causes of anosmia (i.e., mucosal disease) do not seem play a significant role.
Nemati M, Ansary J, Nemati N. Machine Learning Approaches in COVID-19 Survival Analysis and Discharge Time Likelihood Prediction using Clinical Data. Pattern July 10, 2020. Full-text: https://doi.org/10.1016/j.patter.2020.100074
How many patients stay how long in which hospital unit? This work introduces statistical models and machine learning (ML)-based approaches that can be directly applied to real-world COVID-19 data to predict the patient discharge time from hospital and evaluate how the patient clinical information could have an impact on the length of stay in hospital. These estimations are important for decision-makers for efficient allocation of equipment and managing hospital overload.
Wortham JM, Lee JT, Althomsons S, et al. Characteristics of Persons Who Died with COVID-19 — United States, February 12–May 18, 2020. MMWR Morb Mortal Wkly Rep. ePub: 10 July 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6928e1
Using national case-based surveillance and supplementary data reported from 16 jurisdictions, detailed characteristics of 10,647 COVID-19 deaths that occurred during February 12–April 24, 2020 are described. More than one third of Hispanic decedents (34.9%) and nearly one third (29.5%) of non-white decedents were aged < 65 years, but only 13.2% of white decedents were aged < 65 years. Most decedents had one or more underlying medical conditions reported (76.4%) or were aged ≥ 65 years (74.8%). Among reported underlying medical conditions, cardiovascular disease and diabetes were the most common.
Kirschenbaum D, Imbach LL, Ulrich S, et al. Inflammatory olfactory neuropathy in two patients with COVID-19. Lancet July 10, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31525-7
Post-mortem histological analysis of the olfactory epithelium in two COVID-19 patients showed prominent leukocytic infiltrates in the lamina propria and focal atrophy of the mucosa. However, it is unclear whether the observed inflammatory neuropathy is a result of direct viral damage or is mediated by damage to supporting non-neural cells.
Hengeveld PJ, Omar Khader A, de Bruin LHA, et al. Blood cell counts and lymphocyte subsets of patients admitted during the COVID-19 pandemic: a prospective cohort study. Br J Haematol. 2020 Jul 11. PubMed: https://pubmed.gov/32652585. Full-text: https://doi.org/10.1111/bjh.16983
Based on ICU admission or death during hospital admission, 197 COVID-19 patients were compared with 354 patients in whom COVID-19 was ruled out (controls). At admission, anemia, leukocytosis and neutrophilia were more prevalent in controls than in COVID-19 patients. In agreement with recent reports, thrombocyte counts were lower in COVID-19 patients, and thrombocytopenia was associated with an increased risk of in-hospital mortality.
Carfi A, Bernabei R, Landi F. Persistent Symptoms in Patients After Acute COVID-19. JAMA July 9, 2020. Full-text: https://doi.org/10.1001/jama.2020.12603 l (Important)
Long time to recover: 143 patients discharged from the hospital after recovery from COVID-19 were assessed for follow-up post–acute care after a mean of 60 days after onset of the first COVID-19 symptom. Only 18 (12.6%) were completely free of any COVID-19 related symptom, while 32% had 1 or 2 symptoms and 55% had 3 or more. None of the patients had fever or any signs or symptoms of acute illness. Worsened quality of life was observed among 44.1% of patients. Many patients still reported fatigue (53%), dyspnea (43%), joint pain (27%) and chest pain (28%).
Gupta A, Madhavan MV, Sehgal K. et al. Extrapulmonary manifestations of COVID-19. Nat Med Jul 10, 2020. https://doi.org/10.1038/s41591-020-0968-3 l (Important)
This article reviews the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 (248 references!). These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications.
Faghy MA, Ashton RE, Maden-Wilkinson TM, et al. Integrated sports and respiratory medicine in the aftermath of COVID-19. Lancet Resp Med July 09, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30307-6
The long-term effects on recovering patients remains unknown. According to this commentary, we must marshal our resources and develop strong collaborative approaches that combine clinical and sports medicine disciplines.
Williamson EJ, Walker AJ, Bhaskaran K et al. OpenSAFELY: factors associated with COVID-19 death in 17 million patients. Nature 08 July 2020 (2020). Full-text: https://doi.org/10.1038/s41586-020-2521-4 l (Important)
Using a secure health analytics platform covering 40% of all patients in England, primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19-related deaths. COVID-19-related death was associated with being male (hazard ratio 1.59, 95% CI 1.53–1.65); older age and deprivation, ie marginalized, (both with a strong gradient); diabetes; severe asthma; and various other medical conditions. Compared with people with white ethnicity, Black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48 and 1.44, respectively).
Patterson RW, Brown RL, Benjamin L, et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain 08 July 2020. Full-text: https://doi.org/10.1093/brain/awaa240
A broad spectrum of neurological complications: among 43 patients (29 with confirmed diagnosis) admitted to a London hospital, five major categories emerged: 1. Encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities 2. Inflammatory CNS syndromes (n = 12) including encephalitis 3. Ischemic strokes (n = 8) 4. Peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome. 5. Miscellaneous central disorders (n = 5) who did not fit these categories.
Liu YC, Ang M, Ong HS, et al. SARS-CoV-2 infection in conjunctival tissue. Lancet Resp Med July, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30272-1
Is the conjunctival epithelium a potential portal of infection? These authors doubt it. A brief review on current knowledge is given.
Merkler ASE, Parikh NS, Mir S, et al. Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza. JAMA Neurol. Published online July 2, 2020. Full-text: https://doi.org/10.1001/jamaneurol.2020.2730
Again, it’s NOT a flu. In this retrospective cohort study, 1,916 COVID-19 patients and 1,486 influenza patients (with emergency department visits or hospitalizations) were compared. There were 31 (1.6%; 95% CI, 1.1% – 2.3%) acute ischemic strokes with COVID-19, compared to 3 with influenza (0.2%; 95% CI, 0.0% – 0.6%). After adjustment for age, sex, and race, the likelihood of stroke was almost 8-fold higher with COVID-19 (odds ratio, 7.6; 95% CI, 2.3 – 25.2).
Goyal P, Ringel JB, Rajan M, et al. Obesity and COVID-19 in New York City: A Retrospective Cohort Study. Ann Int Med 6 Jul 2020. Full-text: https://www.acpjournals.org/doi/10.7326/M20-2730
More on obesity. In this study of 1,687 adults hospitalized with COVID-19 in New York City, obesity was an independent risk factor for respiratory failure but not for in-hospital mortality. These findings explain the extensive use of invasive mechanical ventilation reported in the US, where the prevalence of obesity exceeds 40%. The risk conferred by obesity was similar across age, sex, and race.
Hoxha A, Wyndham-Thomas C, Klamer S, et al. Asymptomatic SARS-CoV-2 infection in Belgian long-term care facilities. Lancet Inf Dis July 03, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30560-0
Following a mass testing campaign in long-term care facilities in Belgium, no symptoms were reported for 2,185 (74.0%) staff and 4,059 (75.3%) residents. Given the cross-sectional nature of this analysis, however, it was not possible to determine whether any of the asymptomatic individuals went on to develop symptoms. If pre-symptomatic or asymptomatic: risk of under-ascertainment of symptoms, although mitigated by medical assessment, persists.
Vestergaard LS, Nielsen J, Richter L, et al. Excess all-cause mortality during the COVID-19 pandemic in Europe – preliminary pooled estimates from the EuroMOMO network, March to April 2020. Euro Surveill. 2020;25(26). Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.26.2001214
The authors present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March–April 2020. Excess mortality particularly affected ≥ 65-year-olds (91% of all excess deaths), to a lesser extent those 45–64 (8%) and 15–44-year-olds (1%). The cumulative excess mortality from week 1 to week 18, 2020 reached a total of 185,287 deaths, including 24,438 (13%) in persons aged 65–74 years, 55,226 (30%) in persons aged 75–84 years, and 88,598 (48%) in persons aged ≥ 85 years.
Shi D, Wu W, Wang Q, et al. Clinical characteristics and factors associated with long-term viral excretion in patients with SARS-CoV-2 infection: a single center 28-day study. J Inf Dis, 02 July 2020. Full-text: https://doi.org/10.1093/infdis/jiaa388
SARS-CoV-2 RNA clearance time was associated with sex, disease severity and lymphocyte function. Among 99 patients, 61 patients had SARS-CoV-2 clearance (virus-negative group), but 38 patients had sustained positive results (virus-positive group). Male sex (HR, 0.58), immunoglobulin use (0.42), APACHE II score (0.89), and lymphocyte count (1.81) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. Antiviral therapy and corticosteroid treatment were not independent factors.
Boscolo-Rizzo P, Borsetto D, Fabbris C, et al. Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19. JAMA Otolaryngol Head Neck Surg. 2020 Jul 2. PubMed: https://pubmed.gov/32614442. Full-text: https://doi.org/10.1001/jamaoto.2020.1379
At 4 weeks from onset, most patients experience complete resolution or even improvement of altered sense of smell or taste. Of 202 patients completing the survey at baseline, 187 (92.6%) also completed the follow-up survey. The evaluation of 113 patients reporting sudden onset of these symptoms at baseline showed that 55 patients (49%) reported complete resolution of smell or taste impairment, 46 (41%) reported an improvement in the severity, and only 12 (11%) reported the symptom was unchanged or worse. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection.
Baqui P, Bica I, Marra V, et al. Ethnic and regional variations in hospital mortality from COVID-19 in Brazil: a cross-sectional observational study. Lancet Global Health 2020, July 2. Full-text: https://doi.org/10.1016/S2214-109X(20)30285-0
The most extensive study (cross-sectional observational) of COVID-19 hospital survival in Brazil ranks second worldwide in total number of COVID-19 cases and deaths. Survivors were more likely to be younger, be women, and have fewer comorbidities, keeping with worldwide findings. In addition, Pardo ethnicity (mixed race) was the second most important risk factor (after age) for death. The ethnicity effect might be related to differences in susceptibility to COVID-19 and access to health care (including intensive care) across ethnicities.
Feaster M, Goh Y-Y. High proportion of asymptomatic SARS-CoV-2 infections in 9 long-term care facilities, Pasadena, California, USA, April 2020. Emerg Infect Dis 2020, Jul 2. Full-text: https://doi.org/10.3201/eid2610.202694
SARS-CoV-2 prevalence in 9 long-term care facilities demonstrated a high proportion (40.7%, 257/631) of asymptomatic infections among residents and staff members. The prevalence of asymptomatic infection differed markedly between facilities: among staff members from 17.4% to 30.6%, among residents from 19.0% to 85.7%.
Ikeuchi K, Saito M, Yamamoto S, Nagai H, Adachi E. Relative bradycardia in patients with mild-to-moderate coronavirus disease, Japan. Emerg Infect Dis 2020, July 1. Full-text: https://doi.org/10.3201/eid2610.202648
Relative bradycardia is a characteristic physical finding in some intracellular bacterial infections, viral infections, and non-infectious diseases. In this case series of 54 patients with mild-to-moderate COVID-19 in Japan, it was also a common finding. This clinical sign could help clinicians to diagnose this disease. Only body temperature was independently associated with pulse rate by multivariate analysis. The predicted change in pulse rate was 7.37 beats/min for each 1°C increase in body temperature.
Weinberger DM, Chen J, Cohen T, et al. Estimation of Excess Deaths Associated With the COVID-19 Pandemic in the United States, March to May 2020. JAMA Intern Med July 1, 2020. Full-text: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2767980
There were approximately 781,000 deaths in the US from March 1 to May 30, 2020, representing 122,300 (95% prediction interval, 116,800 – 127,000) more deaths than would typically be expected. The number of excess all-cause deaths was 28% higher than the official tally of COVID-19–reported deaths during that period. There was substantial variability between states in the difference between official COVID-19 deaths and the estimated burden of excess deaths.
Woolf SH, Chapman DA, Sabo RT. Excess Deaths From COVID-19 and Other Causes, March-April 2020. JAMA July 1, 2020. Full-text: https://jamanetwork.com/journals/jama/fullarticle/2768086
Same idea: the weekly death data for the 50 US states and the District of Columbia were obtained from the National Center for Health Statistics for January through April 2020 and the preceding 6 years. The authors provide state-by-state estimates of excess deaths and a more detailed account of the 5 states most affected by COVID-19. It was estimated that the number of COVID-19 deaths reported in the first weeks of the pandemic captured only two-thirds of excess deaths in the US.
Lavezzo E, Franchin E, Ciavarella C et al. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature 2020, June 30. Full-text: https://doi.org/10.1038/s41586-020-2488-1
On the 21st of February 2020 a resident of the municipality of Vo’, a small town near Padua, Italy, died of pneumonia due to SARS-CoV-2 infection. At the start and the end of the lockdown, NP swabs were performed for 85.9% and 71.5% of the population (n=2,812), yielding to a prevalence of infection of 2.6% (95% CI 2.1-3.3%) and 1.2% (95% CI 0.8-1.8%), respectively. Of note, 42.5% of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic. Viral load of symptomatic versus asymptomatic infections did not differ.
Hewitt J, Carter B, Vilches-Moraga A, et al. The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study. Lancet June 30, 2020. Full-text: https://doi.org/10.1016/S2468-2667(20)30146-8
Using the clinical frailty scale (CFS), 1,564 patients from the UK and Italy were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). Not very surprising: Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1.55 for CFS 3–4, 1.83 for CFS 5–6, and 2.39 for CFS 7–9. Of note, disease outcomes were better predicted by frailty than either age or comorbidity.
Price-Haywood EG, Burton J, Fort D, et al. Hospitalization and Mortality among Black Patients and White Patients with Covid-19. N Engl J Med 2020; June 25, 382:2534-2543. Full-text: https://doi.org/10.1056/NEJMsa2011686
It’s not ethnicity. Of a total of 3,481 COVID-19 patients, seen within an integrated-delivery health system in Louisiana, 70.4% were black non-Hispanic. Although black patients represent 31% of the patients routinely cared for in the system, they made up 76.9% of hospitalized COVID-19 patients. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. However, black race was NOT associated with higher in-hospital mortality than white race, after adjustment for sociodemographic and clinical differences on admission. Of note, there were racial differences in several laboratory results, indicating a longer wait to access care among black patients, resulting in more severe illness on presentation to health care facilities.
Bielecki M, Züst R, Siegrist D, et al. Social distancing alters the clinical course of COVID-19 in young adults: A comparative cohort study. Clin Inf Dis, June 29, 2020. Full-text: https://doi.org/10.1093/cid/ciaa889 l (Important)
Important finding that was long suspected: viral inoculum during infection or mode of transmission may be key factors determining the clinical course of COVID-19. The authors prospectively studied an outbreak in Switzerland among a population of 508 predominantly male soldiers with a median age of 21 years. Infections were followed in two spatially separated cohorts with almost identical baseline characteristics – before and after implementation of stringent social distancing. Results: of 354 soldiers infected prior to the implementation of social distancing, 30% fell ill. In contrast, none out of 154 soldiers in which infections (confirmed by NP swabs or serology) appeared after implementation of social distancing developed COVID-19.
Lockhart SM, O’Rahilly S. When two pandemics meet: Why is obesity associated with increased COVID-19 mortality? Med 2020,June 25. Full-text: https://doi.org/10.1016/j.medj.2020.06.005 l (Important)
What a nice understatement. The authors describe “some hypotheses regarding the deleterious impact of obesity on the course of COVID-19”. This brilliant overview summarizes current knowledge on the underlying mechanisms. These are: 1. Increased inflammatory cytokines (potentiate the inflammatory response), 2. reduction in adiponectin secretion (abundant in the pulmonary endothelium), 3. increases in circulating complement components, 4. systemic insulin resistance (associated with endothelial dysfunction and with increased plasminogen activator inhibitor-1), and 5. ectopic lipid deposited in type 2 pneumocytes (pre-disposing to lung injury).
Roca-Ginés J, Torres-Navarro I, Sánchez-Arráez J, et al. Assessment of Acute Acral Lesions in a Case Series of Children and Adolescents During the COVID-19 Pandemic. JAMA Dermatol. 2020 Jun 25. PubMed: https://pubmed.gov/32584397. Full-text: https://doi.org/10.1001/jamadermatol.2020.2340 l (Important)
In this case series from Valencia following 20 patients aged 1 to 18 years with new-onset acral inflammatory lesions, all lacked systemic manifestations of COVID-19. Surprisingly, both PCR and serologic test results were negative for SARS-CoV-2, questioning an association between acral skin disease and COVID-19.
Herman A, Peeters C, Verroken A, et al. Evaluation of Chilblains as a Manifestation of the COVID-19 Pandemic. JAMA Dermatol. 2020 Jun 25. PubMed: https://pubmed.gov/32584377. Full-text: https://doi.org/10.1001/jamadermatol.2020.2368
Same in Belgium. Of 31 patients (mostly teenagers) who had recently developed chilblains, histopathologic analysis of skin biopsy specimens (22 patients) confirmed the diagnosis of chilblains and showed occasional lymphocytic or microthrombotic phenomena. In all patients, PCR and serology remained negative. Chilblains appeared not to be directly associated with COVID-19 in this case series. According to the authors, lifestyle changes associated with community containment and lockdown measures are a possible explanation for these lesions.
Varatharaj A, Thomas N, Ellul MA, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry June 25, 2020. Full-text: https://doi.org/10.1016/S2215-0366(20)30287-X
Online network study from the UK, including 125 patients with data and with neurologic/neuropsychiatric complications. Of these, 77 (62%) presented with a cerebrovascular event, of whom 57 (74%) had an ischemic stroke, nine (12%) an intracerebral hemorrhage, and one (1%) CNS vasculitis. Altered mental status was the second most common presentation (31%), comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients.
Maugeri G, Castrogiovanni P, Battaglia G. The impact of physical activity on psychological health during Covid-19 pandemic in Italy. Heliyon June 24, 2020. Full-text: https://doi.org/10.1016/j.heliyon.2020.e04315
Maintain your exercise routine! Among 2524 subjects completing an online survey, total physical activity significantly decreased between before and during the COVID-19 pandemic. A significant positive correlation was found between the variation of physical activity and mental well-being, suggesting that the reduction of total physical activity had a profoundly negative impact on psychological health and well-being of population.
Mallapaty S. Mounting clues suggest the coronavirus might trigger diabetes. Nature 2020, June 24. Full-text: https://www.nature.com/articles/d41586-020-01891-8
Does COVID-19 lead to diabetes? Some comments on preprint papers indicating growing evidence from tissue studies and some clinical cases that the virus damages insulin-producing cells. It remains to be seen how relevant this problem is.
Borras-Bermejo B, Martínez-Gómez X, Gutierrez-San Miguel M, et al. Asymptomatic SARS-CoV-2 infection in nursing homes, Barcelona, Spain, April 2020. Emerg Infect Dis. 2020 Sep [June 23, 2020]. https://doi.org/10.3201/eid2609.202603
High number of asymptomatic patients: the authors obtained a total of 5,869 samples, 3,214 from residents and 2,655 from facility staff in 69 nursing homes. Overall, 768 (23.9%) residents and 403 (15.2%) staff members tested positive for SARS-CoV-2. The presence of fever or respiratory symptoms during the preceding 14 days was recorded in 2,624 residents (81.6%) and 1,772 staff members (66.7%). Among those testing positive with information about symptoms, 69.7% of the residents and 55.8% of staff were asymptomatic. However, the ascertainment process could lead to misclassification due to atypical symptoms in the elderly. Moreover, cross-sectional symptom assessment did not allow the authors to differentiate between presymptomatic and asymptomatic cases.
Grant MC, Geoghegan L, Arbyn M, et al. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLoS One. 2020 Jun 23;15(6. PubMed: https://pubmed.gov/32574165. Full-text: https://doi.org/10.1371/journal.pone.0234765 l (Important)
What hard work. Of 851 unique citations, 148 articles were included which comprised 24,410 adults with confirmed COVID-19 from 9 countries. The most prevalent symptoms were fever (78%), cough (57%) and fatigue (31%). Overall, 19% of hospitalized patients required non-invasive ventilation (44 studies, 6,513 patients), 17% required intensive care (33 studies, 7504 patients), 9% required invasive ventilation (45 studies, 6933 patients) and 2% required ECMO (12 studies, 1,486 patients).
Kronbichler A, Kresse D, Yoon S, Lee KH, Effenberger M, Shin JI. Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis. Int J Infect Dis. 2020 Jun 17:S1201-9712(20)30487-2. PubMed: https://pubmed.gov/32562846. Full-text: https://doi.org/10.1016/j.ijid.2020.06.052
In total, 506 patients from 34 studies (68 single cases and 438 from case series) with an asymptomatic course were identified. Main findings: Asymptomatic patients tend to be younger and may be more socially active. Laboratory findings in most asymptomatic cases were unremarkable. However, 62% had lung opacities, most frequently ground glass opacities.
Lee YH, Hong CM, Kim DH, Lee TH, Lee J. Clinical Course of Asymptomatic and Mildly Symptomatic Patients with Coronavirus Disease Admitted to Community Treatment Centers, South Korea. Emerg Infect Dis. 2020 Jun 22;26(10). PubMed: https://pubmed.gov/32568662. Full-text: https://doi.org/10.3201/eid2610.201620
Of 632 asymptomatic and mildly symptomatic patients admitted to community treatment centers for isolation in South Korea, 75 (12%) had symptoms at admission, 186 (29%) were asymptomatic at admission but developed symptoms during their stay, and 371 (59%) remained asymptomatic during their entire clinical course. The mean virologic remission period was 20.1 days (SD + 7.7 days). The virologic remission period was longer in symptomatic patients than in asymptomatic patients. In mildly symptomatic patients, the mean duration from symptom onset to virologic remission was 11.7 days (SD + 8.2 days).
Bangalore S, Sharma A, Slotwiner A. ST-Segment Elevation in Patients with Covid-19 — A Case Series. N Engl J Med June 18, 2020; 382:2478-2480. Full-text: https://doi.org/10.1056/NEJMc2009020
Among 18 patients with COVID-19 who had ST-segment elevation indicating potential acute myocardial infarction 6/9 patients who underwent coronary angiography had obstructive disease. However, prognosis was dismal: A total of 13 patients (72%) died in the hospital (4 with myocardial infarction and 9 with noncoronary myocardial injury).
Ghannam M, Alshaer Q, Al-Chalabi M, Zakarna L, Robertson J, Manousakis G. Neurological involvement of coronavirus disease 2019: a systematic review. J Neurol. 2020 Jun 19. PubMed: https://pubmed.gov/32561990. Full-text: https://doi.org/10.1007/s00415-020-09990-2
In a systematic review of the literature, 82 cases of COVID-19 with neurological complications were identified. Conclusion: Neurological manifestations of COVID-19 are not rare, especially large vessel stroke, Guillain–Barré syndrome, and meningoencephalitis.
Schaefer IM, Padera RF, Solomon IH, et al. In situ detection of SARS-CoV-2 in lungs and airways of patients with COVID-19. Mod Pathol. 2020 Jun 19. PubMed: https://pubmed.gov/32561849. Full-text: https://doi.org/10.1038/s41379-020-0595-z
In 5/5 patients with acute phase DAD (≤ 7 days from onset of respiratory failure), SARS-CoV-2 was detected in pulmonary pneumocytes and ciliated airway cells, and in 2/5 in upper airway epithelium. In two patients with organizing DAD (> 14 days from onset of respiratory failure), no virus was detected in the lungs or airways. No endothelial cell infection was observed. The findings suggest that the virus is absent in the organizing phase.
Berzuini A, Bianco C, Paccapelo C, et al. Red cell bound antibodies and transfusion requirements in hospitalized patients with COVID-19. Blood. 2020 Jun 19:. PubMed: https://pubmed.gov/32559762. Full-text: https://doi.org/10.1182/blood.2020006695
The direct antiglobulin test (DAT) detects immunoglobulin or complement bound in vivo to red blood cells (RBC), and is widely used to diagnose immune mediated hemolytic anemias. A positive DAT was found in 52 of 113 COVID-19 patients (46%) using the microcolumn screening assay. Thus, anti-RBC antibodies were detectable in almost half of the patients. Although the serologic features of DAT reactivity in COVID-19 patients were somewhat different from those generally observed in autoimmune hemolytic anemia, DAT positivity was associated with increasing frequency of anemia and greater transfusion requirements.
Sardanelli D, Cozzi A, Monfardini L, et al. Association of mediastinal lymphadenopathy with COVID-19 prognosis. Lancet Inf Dis June 19, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30521-1
Among 410 patients with COVID-19 who underwent CT at emergency department admission in three hospitals in Lombardy, Italy, 76 (19%) patients had mediastinal lymphadenopathies (ie, lymph nodes with a short-axis diameter > 1 cm). Data suggest that lymphadenopathy may be considered a predictor of a worse outcome. The pathophysiological meaning of this finding remains to be investigated.
Tan T, Khoo B, Mills EG, et al. Association between high serum total cortisol concentrations and mortality from COVID-19. Lancet Diabetes and Endocrinology 2020, June 18. Full-text: https://doi.org/10.1016/S2213-8587(20)30216-3
In 535 patients, multivariable analysis showed that a doubling of cortisol concentration was associated with a significant 42% increase in the hazard of mortality, after adjustment for age, the presence of comorbidities, and laboratory tests. Cortisol seemed to be a better independent predictor than other laboratory markers associated with COVID-19, such as CRP, D-dimer, and neutrophil to leukocyte ratio.
Hubiche T, Le Duff F, Chiverini C, et al. Negative SARS-CoV-2 PCR in patients with chilblain-like lesions. Lancet Inf Dis 2020, Published: June 18, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30518-1 l (Important)
Among 40 young patients with chilblain lesions and with suspected SARS-CoV-2 infection, COVID-19 serology was positive in 12 (30%) patients. All had negative PCR results at the time of presentation, suggesting that in young patients SARS-CoV-2 is completely suppressed before a humoral immune response is induced.
Elinghaus D, Degenhardt F, Bujanda L, et al. Genomewide Association Study of Severe Covid-19 with Respiratory Failure. NEJM, June 17, 2020. Full-text: https://doi.org/10.1056/NEJMoa2020283 l (Important)
The authors identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with COVID-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. A blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79). However, please don’t measure the blood groups of your patients now. The risk elevations are low (male gender possibly, see below). These results are much more relevant with regard to the underlying pathophysiology (the locus also contains genes encoding chemokine receptors).
Clark A, Jit M, Warren-Gash C, et al. Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study. The Lancet Global Health June 15, 2020. Full-text: https://doi.org/10.1016/S2214-109X(20)30264-3
No good prospects. Analyzing data from 188 nations, the team estimates that 1.7 billion people worldwide have an elevated risk of ‘severe’ illness. The researchers also estimate that 349 million (186–787) people (4% of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from < 1% of those younger than 20 years to approximately 20% of those aged 70 years or older). In total, 6% of males were found to be at high risk compared with 3% of females.
Suleyman G, Fadel RA, Malette KM, et al. Clinical Characteristics and Morbidity Associated With Coronavirus Disease 2019 in a Series of Patients in Metropolitan Detroit. JAMA Netw Open. 2020 Jun 1;3(6):e2012270. PubMed: https://pubmed.gov/32543702. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.12270-
Case series of 463 consecutive patients with COVID-19 (72.1% African American), evaluated at Henry Ford Health System in metropolitan Detroit, Michigan. Most patients (94%) had at least 1 comorbidity, including hypertension (64%), chronic kidney disease (39.3%), and diabetes (38%). 355 patients (77%) were hospitalized; 141 (40%) required intensive care unit management and 114 (81%) of those patients required invasive mechanical ventilation. Male sex (OR, 1.8) and age older than 60 years (OR 5.3) were significantly associated with mortality, whereas African American race was not.
Patel MC, Chaisson LH, Borgetti S, et al. Asymptomatic SARS-CoV-2 infection and COVID-19 mortality during an outbreak investigation in a skilled nursing facility. Clin Infect Dis. 2020 Jun 16:ciaa763. PubMed: https://pubmed.gov/32548628. Full-text: https://doi.org/10.1093/cid/ciaa763
Of 126 residents tested at a skilled nursing facility in Illinois, 33 had confirmed SARS-CoV-2. Nineteen (58%) had symptoms at the time of testing, 1 (3%) developed symptoms over follow-up, and 13 (39%) remained asymptomatic. Thirty-five residents who tested negative on March 15 developed symptoms over follow-up; of these, 3 were re-tested and 2 were positive. The 30-day probability of death among cases was 29%.
Sakurai A, Sasaki T, Kato S, et al. Natural History of Asymptomatic SARS-CoV-2 Infection. NEJM June 12, 2020. Full-text: https://DOI.ORG/10.1056/NEJMc2013020
More on asymptomatic infection: The authors followed 90 persons from the cruise ship Diamond Princess who were asymptomatic at the time of the positive PCR test and remained so until the resolution of infection (as determined by two consecutive negative PCR tests). 27% had coexisting medical conditions. The median time between the first positive PCR test result (either on the ship or at the hospital) and the first of the two serial negative PCR results was 9 days (range, 3 to 21), and the cumulative percentages of persons with resolution of infection 8 and 15 days after the first positive PCR were 48% and 90%, respectively.
Tabata S, Imai K, Kawano S, et al. Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis. Lancet Inf Dis 2020, June 12. Full-text: https://doi.org/10.1016/S1473-3099(20)30482-5.
Among 104 people from the Diamond Princess cruise ship who were admitted to a Tokyo hospital, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period.
Solomon IH, Normandin E, Bhattacharyya B, et al. Neuropathological Features of Covid-19. NEJM June 12, 2020. Full-text: https://DOI.ORG/10.1056/NEJMc2019373
Histopathological examination of brain specimens obtained from 18 patients who died 0 to 32 days after the onset of symptoms showed only hypoxic changes and did not show encephalitis or other specific brain changes referable to the virus. The virus was detected at low levels in 6 brain sections obtained from 5 patients; it remains to be seen whether this was due to in situ virions or viral RNA from blood.
Wright Hr KP, Linton SK, Withrow D. Sleep in University Students Prior to and During COVID-19 Stay-at-Home Orders. Current Biology, June 10, 2020 Full-text: https://doi.org/10.1016/j.cub.2020.06.022
Good to know: during lockdown, they sleep better. This ground-breaking study investigated sleep behaviors prior to and during Stay-at-Home orders in 139 university students. During Stay-at-Home, nightly time in bed devoted to sleep increased by 30 min during weekdays and by 24 mins on weekends and regularity of sleep timing improved by 12 min. Sleep timing became later by 50 min during weekdays and 25 min on weekends, and thus the difference between weekend and weekday sleep timing decreased—hence reducing the amount of social jetlag. A subsequent study on changes in breakfast behaviors is eagerly awaited (proposed hypothesis: less coffee, more jam).
Destras G, Bal A, Excuret V, et al. Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic. The Lancet Microbe June 11, 2020. Full-text: https://doi.org/10.1016/S2666-5247(20)30066-5
Among 578 CSF samples analyzed at the virology laboratory of Lyon University Hospital during the COVID-19 epidemic (Feb 1 to May 11, 2020), all were negative, except for two samples that were slightly positive for SARS-CoV-2 corresponding to post-mortem samples from two adults with confirmed COVID-19. Importantly, the other 21 CSF samples from patients with confirmed COVID-19 were negative. These data suggest that, although SARS-CoV-2 is able to replicate in neuronal cells in vitro, SARS-CoV-2 testing in CSF is not relevant in the general population.
Covino M, De Matteis G, Santoro M, et al. Clinical characteristics and prognostic factors in COVID-19 patients aged ≥80 years. Geriatr Gerontol Int. 2020 Jun 9. PubMed: https://pubmed.gov/32516861. Full-text: https://doi.org/10.1111/ggi.13960
Of 69 patients aged 80-98 years who presented at a large center in Rome, Italy, 36% had a critical COVID-19 disease. Multivariate Cox regression analysis showed that, among other factors, severe dementia was an independent risk factor for death (Hazard Ratio 3.9, 95 % CI 1.2-12.2).
Gervaise A, Bouzad C, Peroux E, Helissey C. Acute pulmonary embolism in non-hospitalized COVID-19 patients referred to CTPA by emergency department. Eur Radiol. 2020 Jun 9. PubMed: https://pubmed.gov/32518989. Full-text: https://doi.org/10.1007/s00330-020-06977-5
Acute pulmonary embolism (APE) is not limited to severe or critical COVID-19. Five of 13 (38%) patients with APE in this small study had a moderate clinical COVID-19 type.
Lala A, Johnson KW, Januzzi JL, et al. Prevalence and Impact of Myocardial Injury in Patients Hospitalized with COVID-19 Infection. J Am Coll Cardiol. 2020 Jun 5:S0735-1097(20)35552-2. PubMed: https://pubmed.gov/32517963. Full-text: https://doi.org/10.1016/j.jacc.2020.06.007
Myocardial injury is prevalent. Among 2,736 COVID-19 patients admitted to one of five Mount Sinai Health System hospitals in New York City who had troponin-I measured within 24 hours of admission, 985 (36%) patients had elevated troponin concentrations. After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (0.03-0.09 ng/mL) were significantly associated with death (adjusted HR: 1.75, 95% CI 1.37-2.24) while greater amounts (>0.09 ng/dL) were significantly associated with higher risk (adjusted HR 3.03, 95% CI 2.42-3.80).
Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review. Ann Intern Med. 2020 Jun 3. PubMed: https://pubmed.gov/32491919. Full-text: https://doi.org/10.7326/M20-3012
Review of the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40-45% of infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. The absence of COVID-19 symptoms might not necessarily imply an absence of harm as subclinical lung abnormalities are frequent.
Kola L. Global mental health and COVID-19. Lancet Psychiatry June 02, 2020. Full-text: https://doi.org/10.1016/S2215-0366(20)30235-2
Intelligent comment. The psychosocial burden of COVID-19 will become increasingly evident in the coming months as the effects of social measures such as physical distancing, loneliness, death of friends and family members, and job losses manifest. Bad news, no good prospects (but the best author name of the month!).
Argenziano MG, Bruce SL, Slater CL, et al. Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series. BMJ. 2020 May 29. PubMed: https://pubmed.gov/32471884. Full-text: https://doi.org/10.1136/bmj.m1996
Characterization of the first 1000 consecutive patients with COVID-19 who received care at the emergency department in NYC hospital. Rates of renal complications were high: 33.9% of all patients and 78% of patients in intensive care units developed acute kidney injury. Concomitantly, 13.8% of all patients and 35.2% of patients in intensive care units required in-patient dialysis, leading to a shortage of equipment for dialysis and continuous renal replacement therapy.
Szekely Y, Lichter Y, Taieb P, et al. The Spectrum of Cardiac Manifestations in Coronavirus Disease 2019 (COVID-19) – a Systematic Echocardiographic Study. Circulation. 2020 May 29. PubMed: https://pubmed.gov/32469253. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047971
100 consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared to reference values. Thirty two patients (32%) had a normal echocardiogram at baseline. The most common cardiac pathology was RV right ventricular (RV) dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%). The authors concluded that LV systolic function is preserved in the majority of patients, but LV diastolic and RV function are impaired.
Phipps MM, Barraza LH, LaSota ED, et al. Acute Liver Injury in COVID-19: Prevalence and Association with Clinical Outcomes in a Large US Cohort. Hepatology. 2020 May 30. PubMed: https://pubmed.gov/32473607. Full-text: https://doi.org/10.1002/hep.31404
One of the largest studies evaluating liver injury. Among 2,273 patients who tested positive, 45% had mild, 21% moderate, and 6.4% severe liver injury. In multivariate analysis, severe acute liver injury was significantly associated with elevated inflammatory markers including ferritin and IL‐6. Peak ALT was significantly associated with death or discharge to hospice (OR 1.14, p = 0.044), controlling for age, body mass index, diabetes, hypertension, intubation, and renal replacement therapy.
Marijon E, Karam N, Jost D, et al. Out-of-hospital cardiac arrest during the COVID-19 pandemic in Paris, France: a population-based, observational study. Lancet Public Health. 2020 May 27:S2468-2667(20)30117-1. PubMed: https://pubmed.gov/32473113. Full-text: https://doi.org/10.1016/S2468-2667(20)30117-1
Staying at home is not always the best decision. During the COVID-19 pandemic in the Paris area, authors observed a significant (two-fold) and transient increase in the incidence of out-of-hospital cardiac arrest (OHCA), coupled with a major reduction in survival at hospital admission. Although this finding might be partly related to direct COVID-19 deaths, indirect effects related to lockdown and reorganisation of healthcare systems may account for a substantial part.
Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020 May 27:S0163-4453(20)30323-6. PubMed: https://pubmed.gov/32473235. Full-text: https://doi.org/10.1016/j.jinf.2020.05.046
According to this review, low proportions of COVID-19 patients have a bacterial co-infection, less than in previous influenza pandemics. These findings do not support the routine use of antibiotics in the management of confirmed COVID-19 infection.
Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and Mortality among Black Patients and White Patients with Covid-19. N Engl J Med. 2020 May 27. PubMed: https://pubmed.gov/32459916. Full-text: https://doi.org/10.1056/NEJMsa2011686
It’s poverty and obesity, but not race. In a large cohort of 3,481 patients in Louisiana, 76.9% of the patients who were hospitalized with COVID-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the population. Of note, black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.
Zubair AS, McAlpine LS, Gardin T, et al. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurology May 29, 2020. Full-text: https://10.1001/jamaneurol.2020.2065 l (Important)
Viral neuro-invasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. This review summarizes available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system.
Politi LS, Salsano E, Grimaldi M. Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurology May 29, 2020. Full-text: https://10.1001/jamaneurol.2020.2125
Interesting case report, describing in vivo brain alteration during COVID-19. A patient with COVID-19 showed a signal alteration compatible with viral brain invasion in a cortical region (ie, posterior gyrus rectus). Slight and reversible olfactory bulb changes were also seen.
Yang R, Gui X, Xiong Y, et al. Comparison of Clinical Characteristics of Patients with Asymptomatic vs Symptomatic Coronavirus Disease 2019 in Wuhan, China. JAMA Netw Open, May 27 2020. Full-text: https://10.1001/jamanetworkopen.2020.10182i l (Important)
Case series, including carefully selected data for 78 patients (33 asymptomatic) from 26 cluster cases of exposure to the Hunan seafood market or close contact with other patients with COVID. Asymptomatic patients were younger and had a median shorter duration of viral shedding from nasopharynx swabs (median duration, 8 days vs 19 days)
Lechien JR, Chiesa-Estomba CM, Hans S, et al. Loss of Smell and Taste in 2013 European Patients With Mild to Moderate COVID-19. Annals Int Med 2020, May 26. Full-text: https://doi.org/10.7326/M20-2428
The largest study to date, analysing these important symptoms. Of 2,013 patients, 1,754 patients (87%) reported loss of smell, whereas 1,136 (56%) reported taste dysfunction. Most patients had loss of smell after other general and otolaryngologic symptoms. Mean duration of olfactory dysfunction was 8.4 days. The prevalence of self-reported smell and taste dysfunction was higher than previously reported and may be characterized by different clinical forms. Anosmia may not be related to nasal obstruction or inflammation. Of note, only two thirds of patients reporting olfactory symptoms and who had objective olfactory testing had abnormal results.
Kuo CL, Pilling LC, Atkins JL, et al. APOE e4 genotype predicts severe COVID-19 in the UK Biobank community cohort. The Journals of Gerontology: May 26, 2020. Full-text: https://doi.org/10.1093/gerona/glaa131
The authors investigated the association between different ApoEe4 alleles and COVID-19 severity, using the UK Biobank data. ApoEe4e4 homozygotes were more likely to be COVID-19 test positives (OR = 2.31, 95% CI: 1.65 to 3.24) compared to e3e3 homozygotes. The ApoEe4e4 allele increased risks of severe COVID-19 infection, independent of pre-existing dementia, cardiovascular disease, and type 2 diabetes. This interesting observation needs to be confirmed (and explained).
Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020 May 22;369:m1966. PubMed: https://pubmed.gov/32444366. Full-text: https://doi.org/10.1136/bmj.m1966
Of 5,279 cases confirmed in a large medical center in New York, 52% were admitted to hospital, of whom 1,904 (69.5%) were discharged alive without hospice care and 665 (24.3%) were discharged to hospice care or died. Of 647 (23.6%) patients requiring mechanical ventilation, 391 (60.4%) died and 170 (26.2%) were extubated or discharged. The strongest risk for hospital admission was associated with age with an odds ratio of 37.9 for ages 75 years and older. Other risks were heart failure (OR 4.4), male sex (2.8), chronic kidney disease (2.6), and BMI >40 (2.5). Admission oxygen saturation of <88% (3.7), troponin level >1 (4.8), CRP >200 (5.1), and D dimer level >2500 (3.9) were more strongly associated with critical illness than age or comorbidities. Risk of critical illness decreased significantly over the study period. Similar associations were found for mortality alone.
Docherty AB, Harrison EM, Green CA, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020 May 22;369:m1985. PubMed: https://pubmed.gov/32444460. Full-text: https://doi.org/10.1136/bmj.m1985 ll (outstanding)
Clinical data from 20,133 patients, admitted to (or diagnosed in) 208 acute care hospitals in the UK until April 19. Median age was 73 years (interquartile range 58-82) and 60% were men. Comorbidities were common, namely chronic cardiac disease (31%), diabetes (21%), non-asthmatic chronic pulmonary disease (18%). Overall, 41% of patients were discharged alive, 26% died, and 34% continued to receive care. 17% required admission to high dependency or intensive care units; of these, 28% were discharged alive, 32% died, and 41% continued to receive care. Of those receiving mechanical ventilation, 17% were discharged alive, 37% died, and 46% remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital.
Michelozzi P, de’Donato Francesca, Scortichini Matteo, et al. Mortality impacts of the coronavirus disease (COVID-19) outbreak by sex and age: rapid mortality surveillance system, Italy, 1 February to 18 April 2020. Euro Surveill. 2020;25(19). Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.19.2000620
Old white men. From the start of the epidemic until 18 April, an overall 4,805 (+45%) excess deaths were observed in Italian cities, with a significantly higher excess in the north (+76%, +4,295 deaths) compared with the center and the south (+10%, +510 deaths). Overall, the excess in mortality was higher among men than among women in cities in the north vs the center and the south (men: +87% and +70% and women: +17% and +9%, respectively), with an increase in the trend by age. The greatest excess in the north was among elderly men (+76% in 65–74 year-olds, +89% in 75–84 year-olds and +102% in those 85 years and older). In central and southern Italy, the excess in mortality among men was lower, with a statistically significant excess only among elderly men: +13% and +28%, respectively, in the 75–84 years and ≥85 years age group.
Zhang L, Feng X, Zhang D, et al. Deep Vein Thrombosis in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) in Wuhan, China: Prevalence, Risk Factors, and Outcome. Circulation 2020 May 18. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.046702
The next study emphasizes the high thrombosis risk. Of 143 patients hospitalized with COVID-19 (aged 63 ± 14 years; 52% men), 66 patients developed lower extremity Deep Vein Thrombosis (DVT) (46.1%), among them 23 with proximal DVT. Compared with patients without DVT, patients were older and had a lower oxygenation index, a higher rate of cardiac injury, and worse prognosis. Multivariate analysis found CURB-65 score 3-5 (OR = 6.122), Padua prediction score ≥4 (OR = 4.016), and D-dimer >1.0 μg/ml (OR = 5.818) to be associated with DVT.
Caussy C, Pattou RF, Wallet F, et al. Prevalence of obesity among adult inpatients with COVID-19 in France. Lancet Diabetes Endocrinology 2020, May 18. Full-text: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30160-1/fulltext
Analysis of 340 hospitalized patients in Lyon with information on BMI. In multivariable analyses, odds of critical COVID-19 versus non-critical COVID-19 were higher in patients with obesity than in patients without obesity when adjusted for age and sex. The association remained significant after adjustment for the other potential specific risk factors, with age-sex-adjusted ORs ranging between 1·80 and 2·03.
Rogers JP, Chesney E, Oliver D, et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry 2020, May 18. Full-text: https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(20)30203-0/fulltext
It’s time to talk about possible psychiatric and neuropsychiatric implications of the current pandemic. According to this systematic review, preliminary data suggest that patients with COVID-19 might experience delirium, confusion, agitation, and altered consciousness, as well as symptoms of depression, anxiety, and insomnia. High-quality peer-reviewed research into psychiatric symptoms as well as into potential mitigating factors and interventions is needed.
Piccininni M, Rohmann JL, Foresti L, et al. Use of all cause mortality to quantify the consequences of covid-19 in Nembro, Lombardy: descriptive study. BMJ 2020, May 14. Full-text: https://doi.org/10.1136/bmj.m1835
One common argument in the current discussion is that some of the people who died “with” COVID-19 did not actually die “from” it. This would overestimate the “real” mortality. This is probably true. However, the opposite is also true – that many who died from the infection without testing positive never contribute to the official death toll. In the small town of Nembro (around 11,500 residents) that was among the first Italian cities hit by COVID-19, monthly all-cause mortality between 2012 and February 2020 fluctuated around 10 per 1000 person years, with a maximum of 21.5. In March 2020, mortality reached a peak of 154.4 (driven by older men) and decreased to 23.0 in early April. From the outbreak onset until 11 April 2020, only half (85/166) of deaths had a confirmed COVID-19 diagnosis. The full implications of this crisis can only be completely understood if all-cause mortality in a given region and time frame is considered.
Nice overview on a symptom which is frequently overlooked in clinical practice. Headache was observed in 11-34% of hospitalized patients (in 6-10% as presenting symptom). Significant features are moderate to severe, bilateral headache with pulsating or pressing quality in the temporo-parietal, forehead or periorbital region. The most striking features are sudden to gradual onset and poor response to common analgesics. Possible pathophysiological mechanisms include activation of peripheral trigeminal nerve endings by SARS-CoV2 directly or through vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia.
New York City Department of Health and Mental Hygiene (DOHMH) COVID-19 Response Team. Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak — New York City, March 11–May 2, 2020. Morb Mortal Wkly Rep 2020; 69:603-605. Full-text: http://dx.doi.org/10.15585/mmwr.mm6919e5
Anybody out there still doubting excess mortality? Please show them this paper, including the most impressive figure of the day. It depicts the total excess all-cause deaths in New York, calculated as observed deaths minus expected deaths as determined by a seasonal regression model using mortality data from the period January 1, 2015–May 2, 2020.
Smith JC, Sauswille EL, Girish V, et al. Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract. Development Cell, May 16, 2020. Full-text: https://doi.org/10.1016/j.devcel.2020.05.012
Quit smoking, immediately! Lung ACE2 levels do not vary by age or sex, but smokers exhibit upregulated ACE2. Cigarette smoke triggers an increase in ACE2+ cells by driving secretory cell expansion. The overabundance of ACE2 in the lungs of smokers may partially explain why smokers are significantly more likely to develop severe COVID-19.
Lusignan S, Dorward J, Correa A, et al. Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study. Lancet Inf Dis 2020, May 15. Full-text: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30371-6/fulltext – PDF: https://doi.org/10.1016/S1473-3099(20)30371-6
Well, it’s not that easy (quitting smoking and finding clinical correlations to cell experiments). Within a surveillance centre primary care sentinel network, multivariable logistic regression models were used to identify risk factors for positive SARS-CoV-2 tests. Of note, active smoking was associated with decreased odds (yes, decreased: adjusted OR 0.49, 95% CI 0.34–0.71). According to the authors, their findings should not be used to conclude that smoking prevents SARS-CoV-2 infection, or to encourage ongoing smoking. Several explanations are given, such as selection bias (smokers are more likely to have a cough, more frequent testing could increase the proportion of smokers with negative results). Active smoking might also affect RT-PCR test sensitivity.
Marinho PM, Marcos AAA, Romano AC, Nascimento H, Belfort R Jr. Retinal findings in patients with COVID-19. Lancet. 2020 May 12PubMed: https://pubmed.gov/32405105. Full-text: https://doi.org/10.1016/S0140-6736(20)31014-X
COVID-19 and the eye: Using optical coherence tomography (OCT) as a non-invasive imaging technique that is useful for demonstrating subclinical retinal changes, the authors describe their experience in 12 adult patients (9 were physicians). All patients showed hyper-reflective lesions at the level of the ganglion cell and the inner plexiform layers more prominently at the papillomacular bundle in both eyes.
Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and Renal Tropism of SARS-CoV-2. NEJM May 13, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMc2011400
SARS-CoV-2 viral load was quantified in autopsy tissue samples obtained from 22 deceased patients. The highest levels were detected in the respiratory tract, but lower levels were also detected in the kidneys, liver, heart, brain, and blood, indicating a broad organotropism of SARS-CoV-2.
Zhou J, Li C, Liu X et al. Infection of bat and human intestinal organoids by SARS-CoV-2. Nat Medicine 2020. https://doi.org/10.1038/s41591-020-0912-6
Authors demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. They also established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells.
Liang W, Liang H, Ou L, et al. Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. JAMA Intern Med. 2020 May 12. PubMed: https://pubmed.gov/32396163. Full-text: https://doi.org/10.1001/jamainternmed.2020.2033
Using a development cohort of 1590 patients and a validation cohort of 710 patients, a risk score was developed (COVID-GRAM) to predict development of critical illness. The risk factors used in the score were: chest radiography abnormality, age, hemoptysis, dyspnea, unconsciousness, number of comorbidities, cancer history, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and direct bilirubin. The score has been translated into an online risk calculator that is freely available to the public (http://188.8.131.52/)
Menni C, Valdes AM, Freidin MB, et al. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med 2020, May 11. https://doi.org/10.1038/s41591-020-0916-2
A total of 18,401 participants from US/UK reported potential symptoms on a smartphone app and underwent a SARS-CoV-2 test. The proportion of participants who reported loss of smell and taste was higher in those with a positive test result (65% vs 22%). A combination of symptoms, including anosmia, fatigue, persistent cough and loss of appetite was appropriate to identify individuals with COVID-19.
Teufel M, Schweda A, Dörrie N. Not all world leaders use Twitter in response to the COVID-19 pandemic: impact of the way of Angela Merkel on psychological distress, behaviour and risk perception. Journal of Public Health May 12, 2020. Full-text: https://academic.oup.com/jpubhealth/advance-article/doi/10.1093/pubmed/fdaa060/5835923
By no doubt the weirdest paper title of the day. In a large online survey, the authors determined the levels of COVID-19 fear, anxiety and depression in 12,244 respondents during two weeks in March. Concurrent with Angela Merkel’s speech on March 16, a reduction of anxiety and depression was noticeable in the German population.
Parohan M, Yaghoubi S, Seraj A. Liver injury is associated with severe Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of retrospective studies. Hepatol Res. 2020 May 9. PubMed: https://pubmed.gov/32386449. Full-text: https://doi.org/10.1111/hepr.13510
Meta-analysis of 20 retrospective studies with 3,428 COVID-19 infected patients (1,455 severe cases and 1,973 mild cases). Higher serum levels of ALT, AST, bilirubin and lower serum levels of albumin were associated with a significant increase in the severity of COVID-19.
Draulans D. Scientist who fought Ebola and HIV reflects on facing death from COVID-19. Sciencemag 2020, May 8. Full-text: https://www.sciencemag.org/news/2020/05/finally-virus-got-me-scientist-who-fought-ebola-and-hiv-reflects-facing-death-covid-19
Peter Piot, 71, one of the discoverers of the Ebola virus in 1976, former UNAIDS director and coronavirus adviser to European Commission President Ursula von der Leyen, discusses a severe case of COVID-19 occurring in March: his own. Interesting reflections on the disease and on death.
Creel-Bulos C, Hockstein M, Amin N, Melhem S, Truong A, Sharifpour M. Acute Cor Pulmonale in Critically Ill Patients with Covid-19. N Engl J Med. 2020 May 6. PubMed: https://pubmed.gov/32374956. Full-text: https://doi.org/10.1056/NEJMc2010459
Five patients from Atlanta, USA, with profound hemodynamic instability due to the development of acute cor pulmonale. Although acute pulmonary thromboembolism was the most likely cause of right ventricular failure in these patients (4/5 were younger than 65 years of age), this was not definitively confirmed in all cases.
Wichmann D, Sperhake JP, Lutgehetmann M, et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med. 2020 May 6. PubMed: https://pubmed.gov/32374815. Full-text: https://doi.org/10.7326/M20-2003 l (Important)
Autopsy findings from 12 COVID-19 patients who died in Hamburg, Germany. Seven of the twelve had deep vein thrombosis, and pulmonary embolism was the direct cause of death in four cases. Of note, viremia was found in 6 of 10 patients tested and 5/12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.
Ong SW, Young BE, Leo YS. Association of higher body mass index (BMI) with severe coronavirus disease 2019 (COVID-19) in younger patients. Clinical Infectious Diseases 2020, May 8. Full-text: https://doi.org/10.1093/cid/ciaa548
Retrospective analysis of 182 patients from Singapore. Among those aged <60 years, a BMI ≥25 was significantly associated with pneumonia on chest radiograph on admission (p value = 0.017), requiring low-flow supplemental oxygen (OR 6.32, 95% CI 1.23 – 32.34) and mechanical ventilation (OR 1.16, 95% CI 1.00 – 1.34).
Jiang M, Guo Y, Luo Q, et al. T cell subset counts in peripheral blood can be used as discriminatory biomarkers for diagnosis and severity prediction of COVID-19. J Infect Dis. 2020 May 7. PubMed: https://pubmed.gov/32379887. Full-text: https://doi.org/10.1093/infdis/jiaa252
CD3+, CD4+ and CD8+T cells but also NK cells were significantly decreased in COVID-19 patients and related to the severity of the disease. Thresholds of CD8+T and CD4+T used for distinguishing between COVID-19 patients and healthy controls were 285.5/µl and 386.0/µl. According to the authors, CD8+T and CD4+T cell counts can be used as diagnostic markers of COVID-19 and predictors of disease severity.
Metlay JP, Waterer GW. Treatment of Community-Acquired Pneumonia During the Coronavirus Disease 2019 (COVID-19) Pandemic. Ann Intern Med. 2020 May 7. PubMed: https://pubmed.gov/32379883. Full-text: https://doi.org/10.7326/M20-2189
Some ideas on how to treat community-acquired pneumonia (CAP) during these days and how to interpret CAP guidelines.
Discharge from ICU is not the end. Challenges remain for appropriate rehabilitation—physical, cognitive, and psychological. And whether this will be available for the huge numbers of people who will need to deal with the enormous impact of a stay in critical care.
Middeldorp S, Coppens M, van Haaps TF, et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020 May 5. PubMed: https://pubmed.gov/32369666. Full-text: https://doi.org/10.1111/jth.14888 l (Important)
The next study reporting on an incredibly high number of venous thromboembolism (VTE). In this single-center study from Amsterdam on 198 hospitalized cases, the cumulative incidence of VTE at 7, 14, and 21 days were 16%, 33% and 42%. In 74 ICU Patients, cumulative incidence was 59% at 21 days, despite thrombosis prophylaxis. The authors have changed their practice during the follow-up period by performing screening compression ultrasound in the ICU every 5 days.
Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020 May 4. PubMed: https://pubmed.gov/32367170. Full-text: https://doi.org/10.1007/s00134-020-06062-x
Same idea: In this prospective study from France, 64/150 (43%) patients were diagnosed with clinically relevant thrombotic complications. Authors argue for higher anticoagulation targets in critically ill patients.
Ahmed MZ, Khakwani M, Venkatadasari I, et al. Thrombocytopenia as an initial manifestation of Covid-19; Case Series and Literature review. Br J Haematol. 2020 May 5. PubMed: https://pubmed.gov/32369609. Full-text: https://doi.org/10.1111/bjh.16769
Three patients, two of them with hemorrhagic manifestation and severe thrombocytopenia responded to IVIG fairly quickly with a sustained response over weeks.
Martin Carreras-Presas C, Amaro Sanchez J, Lopez-Sanchez AF, Jane-Salas E, Somacarrera Perez ML. Oral vesiculobullous lesions associated with SARS-CoV-2 infection. Oral Dis. 2020 May 5. PubMed: https://pubmed.gov/32369674. Full-text: https://doi.org/10.1111/odi.13382
Three cases of COVID-19-associated ulcers in the oral cavity, with pain, desquamative gingivitis, and blisters.
Hu L, Chen S, Fu Y, et al. Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Hospitalized Patients in Wuhan, China. Clin Infect Dis. 2020 May 3. PubMed: https://pubmed.gov/32361738. Full-text: https://doi.org/10.1093/cid/ciaa539
In multivariate regression, age > 65 years, smoking, critical disease status, diabetes, high hypersensitive troponin I (>0.04 pg/mL), leukocytosis (>10 x 109/L) and neutrophilia (>75 x 109/L) predicted unfavorable clinical outcomes. Of note, the administration of hypnotics was significantly associated with favorable outcomes (p<0.001). Dexzopiclone, a drug for insomnia, was administered at a dose of 1.0 mg per day to 82 patients for the duration of their hospitalization. Overall, favorable outcomes were recorded for these patients, including a better survival rate. Hypnotics may be an effective ancillary treatment for COVID-19.
Du RH, Liang LR, Yang CQ, et al. Predictors of Mortality for Patients with COVID-19 Pneumonia Caused by SARS-CoV-2: A Prospective Cohort Study. Eur Respir J. 2020 Apr 8. PubMed: https://pubmed.gov/32269088. Full-text: https://doi.org/10.1183/13993003.00524-2020
Among their 179 COVID-19 patients, the authors identified four risk factors, age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T cells ≤75 cell·μL-1, and cardiac troponin I ≥0.05 ng·mL-1. Especially the latter two factors were predictors for mortality. Two predictive models for in-hospital mortality are presented.
Menter T, Haslbauer JD, Nienhold R, et al. Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction. Histopathology. 2020 May 4. PubMed: https://pubmed.gov/32364264. Full-text: https://doi.org/10.1111/his.14134
Post-mortem examination of 21 COVID-19 cases, indicating a strong virus-induced vascular dysfunction. Interesting co-finding: 65% of the deceased patients had blood group A. Coincidence? Probably not. Blood group A may be associated with the failure of pulmonary microcirculation and coagulopathies in COVID-1. Another explanation could be the direct interaction between antigen A and the viral S protein, thus facilitating virus entry via ACE2.
Bowles L, Platton S, Yartey N, et al. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19. NEJM May 5, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMc2013656?query=featured_home
Of 216 patients with SARS-CoV-2, 44 (20%) were found to have a prolonged aPTT. After excluding 9 patients, 31/34 (91%) had positive lupus anticoagulant assays. As this is not associated with a bleeding tendency, authors recommend that prolonged aPTT should not be a barrier to the use of anticoagulation therapies in the prevention and treatment of venous thrombosis.
von der Thusen J, van der Eerden M. Histopathology and genetic susceptibility in COVID-19 pneumonia. Eur J Clin Invest. 2020 Apr 30. PubMed: https://pubmed.gov/32353898. Full-text: https://doi.org/10.1111/eci.13259
Brief review on the current knowledge on the remarkable heterogeneity of disease patterns from a clinical, radiological, and histopathological point of view. The idiosyncratic responses of individual patients may be in part related to underlying genetic variations.
Zhang Y, Qin L, Zhao Y, et al. Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with disease severity in COVID-19. J Infect Dis. 2020 Apr 29. PubMed: https://pubmed.gov/32348495. Full-text: https://doi.org/10.1093/infdis/jiaa224
The first study providing some evidence for a predisposition for severe disease. The authors analyzed a genetic variant of IFITM3. This gene encodes an immune effector protein critical to viral restriction and homozygosity for the C allele that has been associated with influenza severity. The CC genotype was found in 12/24 (50%) patients with severe COVID-19, compared to 16/56 (29%) with mild disease. After adjusting for age groups, the odds ratio for severe disease in patients with CC genotype was 6.3 (p < 0.001).
Meng Y, Wu P, Lu W, et al. Sex-specific clinical characteristics and prognosis of coronavirus disease-19 infection in Wuhan, China: A retrospective study of 168 severe patients. PLOS Pathogens 2020, April 28, 2020. https://doi.org/10.1371/journal.ppat.1008520. https://doi.org/10.1371/journal.ppat.1008520
This retrospective cohort highlights sex-specific differences in clinical characteristics and prognosis. Older age and the presence of comorbidities were prognostic risk factors in 86 males but not in 82 females. Some laboratory parameters also showed significant differences.
Wadhera RK, Wadhera P, Gaba P, et al. Variation in COVID-19 Hospitalizations and Deaths Across New York City Boroughs. April 29, 2020. AMA. Published online April 29, 2020. Full-text: https://doi.org/10.1001/jama.2020.7197
By April 25, the Bronx (which has the highest proportion of racial/ethnic minorities, the most persons living in poverty, and the lowest levels of educational attainment) had higher rates (almost two-fold) of hospitalization and death related to COVID-19 than the other four New York City boroughs Brooklyn, Manhattan, Queens and Staten Island.
Oxley J, Mocco J, Majidi S, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med, April 28, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMc2009787
Five cases of large-vessel stroke in younger patients (age 33-49, 2 without any risk factors) who presented in New York City. By comparison, every 2 weeks over the previous 12 months, on average 0.73 patients younger than 50 years of age with large-vessel stroke had been treated.
Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020 Apr 27. PubMed: https://pubmed.gov/32339221. Full-text: https://doi.org/10.1182/blood.2020006000 l (Important)
Excellent review of coagulation abnormalities that occur in association with COVID-19, and clinical management questions likely to arise. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen degradation products, while abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. Current data do not suggest the use of full intensity anticoagulation doses unless otherwise clinically indicated.
Gandhi RT, Lynch JB, del Rio C. Mild or Moderate Covid-19. NEJM April 24, 2020, Full-text: https://doi.org/10.1056/NEJMcp2009249.
Nice review on clinical manifestations, evaluation and management, but also on infection control and prevention efforts.
Lai J, Ma S, Wang Y, et al. Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019. JAMA Netw Open. 2020;3(3):e203976. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.3976.
Protecting health care workers is an important component of public health measure! This cross-sectional survey of 1257 health care workers in Chinese hospitals found considerable proportions of participants with symptoms of depression (50%), anxiety (47%), insomnia (34%), and distress (72%). Participants reported experiencing psychological burden, especially nurses, women, those in Wuhan, and frontline health care workers directly engaged in the care for patients with COVID-19.
Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 Apr 22. PubMed: https://pubmed.gov/32320003. Full-text: https://doi.org/10.1001/jama.2020.6775 l (Important)
The numbers are becoming huge now. This case series from New York included 5,700 COVID-19 patients admitted to 12 hospitals between March 1 and April 4, 2020. Median age was 63 years (IQR 52-75), the most common comorbidities were hypertension (57%), obesity (42%), and diabetes (34%). At triage, 31% of patients were febrile, 17% had a respiratory rate greater than 24 breaths/minute, and 28% received supplemental oxygen. Of 2,634 patients with an available outcome, 14% (median age 68 years, IQR 56-78, 33% female) were treated in ICU, 12% received invasive mechanical ventilation and 21% died. Mortality for those requiring mechanical ventilation was 88.1%.
Pan Y, Yu X, Du X, et al. Epidemiological and clinical characteristics of 26 asymptomatic SARS-CoV-2 carriers. J Infect Dis. 2020 Apr 22. PubMed: https://pubmed.gov/32318703. Full-text: https://doi.org/10.1093/infdis/jiaa205
Retrospective analysis of 26 persistently asymptomatic patients. The median period from contact to the last positive nucleic acid test was 21.5 days (10-36 days). At least 10 patients had typical ground-glass or patchy opacities on CT.
Spinato G, Fabbris C, Polesel J, et al. Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection. JAMA. 2020 Apr 22. PubMed: https://pubmed.gov/32320008. Full-text: https://doi.org/10.1001/jama.2020.6771
Telephone survey, analyzing 202 adult COVID-19 patients with mild symptoms, 5-6 after the positive swab was performed. Any altered sense of smell or taste was reported by 130 patients (64%, 95% CI, 57%-71%, more frequent in women, 73%). This was seen in 12% before, in 23% at the same time and in 27% after other symptoms. An altered sense of smell or taste was reported as the only symptom by 6 patients (3.0%).
Some thoughts on the pathogenesis of hyposmia. According to the authors, the most likely cause for transient hypogeusia and hyposmia in SARS-CoV-2-infected patients is a direct contact and interaction of the virus with gustatory receptors or olfactory receptor cells.
Effenberger M, Grabherr F, Mayr L, et al. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut. 2020 Apr 20. PubMed: https://pubmed.gov/32312790. Full-text: https://doi.org/10.1136/gutjnl-2020-321388
Fecal calprotectin (FC) has evolved as a reliable fecal biomarker allowing detection of intestinal inflammation in inflammatory bowel diseases and infectious colitis. This report on 40 patients provides some evidence that SARS-CoV-2 infection instigates an inflammatory response in the gut, as elevated FC (largely expressed by neutrophil granulocytes) and diarrhea.
Toscano G, Palmerini F, Ravaglia S, et al. Guillain-Barre Syndrome Associated with SARS-CoV-2. N Engl J Med. 2020 Apr 17. PubMed: https://pubmed.gov/32302082. Full-text: https://doi.org/10.1056/NEJMc2009191
Observational cohort from Italy, involving five patients with COVID-19–associated Guillain-Barré syndrome which probably should be distinguished from critical illness neuropathy and myopathy, which tend to appear later in the course of critical COVID-19 illness.
Gutierrez-Ortiz C, Mendez A, Rodrigo-Rey S, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020 Apr 17. PubMed: https://pubmed.gov/32303650. Full-text: https://doi.org/10.1212/WNL.0000000000009619
The next paper on neurological complications seen with COVID-19, probably due to an aberrant immune response.
Chen R, Liang W, Jiang M, et al. Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China. Chest. 2020 Apr 15. PubMed: https://pubmed.gov/32304772. Full-text: https://doi.org/10.1016/j.chest.2020.04.010
It’s only age. Multivariate analysis of a retrospective cohort of 1590 hospitalized subjects with COVID-19 throughout China revealed the following factors associated with mortality: Age 75 or older (HR: 7.86, 95% CI: 2.44-25.35), Age 65-74 years (HR: 3.43, 95% CI: 1.24-9.5), coronary heart disease (HR: 4.28, 95% CI: 1.14-16.13), cerebrovascular disease(HR: 3.1, 95% CI: 1.07-8.94), dyspnea (HR: 3.96, 95% CI:1.42-11), procalcitonin > 0.5ng/ml (HR: 8.72, 95% CI:3.42-22.28), AST > 40 U/L (HR: 2.2, 95% CI: 1.1- 6.73). Not very new, but by now the largest cohort with detailed information.
Chow EJ, Schwartz NG, Tobolowsky FA, et al. Symptom Screening at Illness Onset of Health Care Personnel With SARS-CoV-2 Infection in King County, Washington. JAMA. 2020 Apr 17. PubMed: https://pubmed.gov/32301962. Full-text: https://doi.org/10.1001/jama.2020.6637
Detailed analysis of symptoms of all laboratory-confirmed SARS-CoV-2 infections in HCP residing in King County. Screening only for fever, cough, shortness of breath, or sore throat might have missed 17% of symptomatic HCP at the time of illness onset; expanding criteria for symptoms screening to include myalgias and chills may still have missed 10%.
Chong VCL, Lim EKG, Fan EB, Chan SSW, Ong KH, Kuperan P. Reactive lymphocytes in patients with Covid-19. Br J Haematol. 2020 Apr 16. PubMed: https://pubmed.gov/32297330. Full-text: https://doi.org/10.1111/bjh.16690
Examination of the peripheral blood films of 32 patients found reactive lymphocytes in 72%. This seems to be in stark contrast to the SARS outbreak where reactive lymphocytes of this type were only rarely seen.
Goyal P, Choi JJ, Pinheiro LC, et al. Clinical Characteristics of Covid-19 in New York City. N Engl J Med. 2020 Apr 17. PubMed: https://pubmed.gov/32302078. Full-text: https://doi.org/10.1056/NEJMc2010419
Clinical characteristics of the first 393 consecutive patients who were admitted to two hospitals in New York City, among them 130 needing invasive mechanical ventilation. The latter were more likely to be male, to be obese, and to have elevated liver-function values and inflammatory markers (ferritin, D-dimer, C-reactive protein, and procalcitonin). Diarrhea (23.7%), and nausea and vomiting (19.1%) were more frequent than in the reports from China (it remains unclear whether this difference reflects geographic variation or differential reporting).
Bangalore S, Sharma A, Slotwiner A, et al. ST-Segment Elevation in Patients with Covid-19 – A Case Series. N Engl J Med. 2020 Apr 17. PubMed: https://pubmed.gov/32302081. Full-text: https://doi.org/10.1056/NEJMc2009020
In this case series of 18 patients who had ST-segment elevation, there was variability in presentation, a high prevalence of non-obstructive disease, and a poor prognosis. 6/9 patients undergoing coronary angiography had obstructive disease. Of note, all 18 patients had elevated D-dimer levels.
Gong J, Ou J, Qiu X, et al. A Tool to Early Predict Severe Corona Virus Disease 2019 (COVID-19) : A Multicenter Study using the Risk Nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020 Apr 16. PubMed: https://pubmed.gov/32296824. Full-text: https://doi.org/10.1093/cid/ciaa443
A risk prediction nomogram for severe COVID-19 was evaluated, including older age, and higher serum lactate dehydrogenase, C-reactive protein, the coefficient of variation of red blood cell distribution width, blood urea nitrogen, direct bilirubin and lower albumin. Interesting, but needs to be validated in larger trials.
In this observational series of 58 patients, ARDS due to SARS-CoV-2 infection was associated with encephalopathy, prominent agitation and confusion, and corticospinal tract signs. It remained unclear which of these features were due to critical illness–related encephalopathy, cytokines, or the effect or withdrawal of medication, and which features were specific to SARS-CoV-2 infection.
In China, among 3387 healthcare workers infected with SARS-CoV-2, 23 persons died. Median age was 55 years (range, 29 to 72). Eleven of these persons had been rehired after retirement and 8 were surgeons. Only 2 of the 23 health care workers were physicians in respiratory medicine who had been specifically assigned to treat patients with COVID-19.
Hendren NS, Drazner MH, Bozkurt B, Cooper LT Jr. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation. 2020 Apr 16. PubMed: https://pubmed.gov/32297796. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047349
SARS-CoV-2 has the potential to infect cardiomyocytes, pericytes and fibroblasts via the ACE2 pathway leading to direct myocardial injury, but that pathophysiological sequence remains unproven. A second hypothesis to explain COVID-19 related myocardial injury centers on cytokine excess and/or antibody mediated mechanisms. Clinically, COVID-19 can manifest with an acute cardiovascular syndrome (termed “ACovCS”). This review shows surveillance, diagnostic and management strategies for ACovCS that balances potential patient risks and healthcare staff exposure.
Review focussing on thrombocytopenia which is commonly seen in COVID-19. Three mechanisms are discussed: direct infection of bone marrow cells by the virus and inhibition of platelet synthesis, platelet destruction by the immune system and platelet aggregation in the lungs, resulting in microthrombi and platelet consumption.
Zini G, Bellesi S, Ramundo F, d´Onofrio G. Morphological anomalies of circulating blood cells in COVID-19. Am J Hematol. 2020 Apr 12. PubMed: https://pubmed.gov/32279346. Full-text: https://doi.org/10.1002/ajh.25824
Morphologic changes in the peripheral blood over time in a few COVID-19 patients from Italy. In the early phase of symptom aggravation, a pronounced granulocytic reaction with immaturity, dysmorphism and apoptotic-degenerative morphological evidence was seen. Later the hematologic picture tended to shift toward impressive reactive lymphocyte activation, often with numerical increase, and heterogeneous morphological expression.
Yousefzadegan S, Rezaei N. Case Report: Death Due to Novel Coronavirus Disease (COVID-19) in Three Brothers. Am J Trop Med Hyg. 2020 Apr 10. PubMed: https://pubmed.gov/32277694. Full-text: https://doi.org/10.4269/ajtmh.20-0240
Is there a genetic predisposition for severe diseases? This report from Iran describes three brothers aged 54-66 years, all dying from COVID-19 with a relatively similar pattern after less than 2 weeks of illness. All were previously healthy, without histories of underlying diseases.
Casini A, Alberio L, Angelillo-Scherrer A, et al. Thromboprophylaxis and laboratory monitoring for in-hospital patients with Covid-19 – a Swiss consensus statement by the Working Party Hemostasis. Swiss Med Wkly. 2020 Apr 11;150:w20247. PubMed: https://pubmed.gov/32277760. Full-text: https://doi.org/10.4414/smw.2020.20247 l (Important)
All in-hospital COVID-19 patients should receive pharmacological thromboprophylaxis according to a risk stratification score, unless contraindicated. In patients with creatinine clearance > 30 ml/min, low molecular weight heparin (LMWH) should be administered according to the prescribing information. These guidelines also suggest regularly monitoring prothrombin time, D-dimers, fibrinogen, platelet count, LDH, creatinine and ALT daily or at least 2-3 times per week.
Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms. Int Forum Allergy Rhinol. 2020 Apr 12. PubMed: https://pubmed.gov/32279441. Full-text: https://doi.org/10.1002/alr.22579
“Flu plus ‘loss of smell’ means COVID-19”. Among 263 patients presenting in March (in a single center in San Diego) with flu-like symptoms, loss of smell was found in 68% of COVID-19 patients (n=59), compared to only 16% in negative patients (n=203). Smell and taste impairment were independently and strongly associated with positivity (anosmia: adjusted odds ratio 11, 95%CI: 5‐24). Conversely, sore throat was independently associated with negativity.
Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Apr 10. PubMed: https://pubmed.gov/32275288. Full-text: https://doi.org/10.1001/jamaneurol.2020.1127
This retrospective, observational case series found 78/214 patients (36%) with neurologic manifestations, ranging from fairly specific symptoms (loss of sense of smell or taste, myopathy, and stroke) to more non-specific symptoms (headache, low consciousness, dizziness, or seizure). Whether these more non-specific symptoms are manifestations of the disease itself remains to be seen.
Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr 9. PubMed: https://pubmed.gov/32271988. Full-text: https://doi.org/10.1111/jth.14830
Among 81 severe COVID-19 patients, incidence of venous thromboembolism (VTE) was 25%. A significant increase of D-dimer was a good index for identifying high-risk groups of VTE.
Wang Y, Lu X, Chen H, et al. Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19. Am J Respir Crit Care Med. 2020 Apr 8. PubMed: https://pubmed.gov/32267160. Full-text: https://doi.org/10.1164/rccm.202003-0736LE
Large single-center case study on 344 severe and critically ill patients admitted to Tongji hospital from January 25 through February 25, 2020. 133 (38.7%) patients died at a median of 15 days. Beside older age, hypertension and COPD were more common in non-survivors but not diabetes. No difference was seen between patients with or without ACE inhibitors.
Ji D, Zhang D, Xu J, et al. Prediction for Progression Risk in Patients with COVID-19 Pneumonia: the CALL Score. Clin Infect Dis. 2020 Apr 9. PubMed: https://pubmed.gov/32271369. Full-text: https://doi.org/10.1093/cid/ciaa414
CURB-65 severity score may not be suitable for COVID-19. In 208 patients, a risk factors scoring system was developed, for prediction of progression, based on patients’ age, comorbidities, lymphocyte count and serum LDH at presentation. Needs to be validated by larger studies.
Zhang Y, Xiao M, Zhang S, et al. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020 Apr 8. PubMed: https://pubmed.gov/32268022. Full-text: https://doi.org/10.1056/NEJMc2007575
Case series on 3 patients with critical illness, developing antiphospholipid antibodies. These antibodies may rarely lead to thrombotic events that are difficult to differentiate from other causes of multifocal thrombosis in critically patients, such as disseminated intravascular coagulation, heparin-induced thrombocytopenia, and thrombotic microangiopathy.
Lechien JR, Chiesa-Estomba CM, De Siati DR, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020 Apr 6. PubMed: https://pubmed.gov/32253535. Full-text: https://doi.org/10.1007/s00405-020-05965-1 l (Important)
This important study shows that in Europe, otolaryngologic symptoms are much more common than in Asia (it remains unclear whether this is a true difference). Among 417 mild-to-moderate COVID-19 patients (from 12 European hospitals), 86% and 88% reported olfactory and gustatory dysfunctions, respectively. The vast majority was anosmic (hyposmia, parosmia, phantosmia did also occur), and the early olfactory recovery rate was 44%. Females were more affected than males. Olfactory dysfunction appeared before (12%), at the same time (23%) or after (65%) the appearance of other symptoms. There is no doubt that sudden anosmia or ageusia need to be recognized as important symptoms of COVID-19.
Neuroinvasive propensity has been demonstrated as a common feature of human coronaviruses. These viruses can invade brainstem via a synapse-connected route from the lung and airways. With regard to SARS-CoV-2, early occurrences such as olfactory symptoms (see above) should be further evaluated for CNS involvement. Potential late neurological complications in cured COVID-19 patients are discussed. No data are available yet. However, after reading this, you will ask yourself whether herd immunity (infection of broader populations) is such a good idea.
Miller DG, Pierson L, Doernberg S. The Role of Medical Students During the COVID-19 Pandemic. Ann Intern Med. 2020 Apr 7. PubMed: https://pubmed.gov/32259194. Full-text: https://doi.org/10.7326/M20-1281
The American Association of Medical Colleges (AAMC) recommends that “unless there is a critical health care workforce need locally, we strongly suggest that medical students not be involved in any direct patient care activities”. The authors disagree (for good reasons).
Cheung KS, Hung IF, Chan PP, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis. Gastroenterology. 2020 Apr 3. PubMed: https://pubmed.gov/32251668. Full-text: https://doi.org/10.1053/j.gastro.2020.03.065
In a meta-analysis of 60 studies comprising 4,243 patients, the pooled prevalence of gastrointestinal symptoms was 17.6% (95% CI, 12.3% – 24.5%). Prevalence was lower in studies from China than other countries. Pooled prevalence of stool samples that were positive for virus RNA was 48.1% and could persist for up to ≥ 33 days from onset of illness even after viral RNA negativity in respiratory specimens. Stool viral RNA was detected at higher frequency among those with diarrhea.
Shanafelt T, Ripp J, Trockel M. Understanding and Addressing Sources of Anxiety Among Health Care Professionals During the COVID-19 Pandemic. JAMA. 2020 Apr 7. PubMed: https://pubmed.gov/32259193. Full-text: https://doi.org/10.1001/jama.2020.5893
This viewpoint summarizes key considerations for supporting the health care workforce.
Short but interesting viewpoint on current clinical insights and key questions. Is PCR always positive? What about reinfection, immunity? What do we know about transmission?
Grasselli G, Zangrillo A, Zanella A, et al. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 6. PubMed: https://pubmed.gov/32250385. Full-text: https://doi.org/10.1001/jama.2020.5394 l (Important)
Important work, providing sobering evidence about the burden of critical illness. Over a period of 28 days, 1,591 COVID-19 patients (88% requiring endotracheal intubation and ventilatory support) were admitted to 72 Italian ICUs, an average of 22 patients per ICU (median length of stay was 9 days). Of note, 82% were male and median age was only 63 years (IQR 56-70), suggesting that older age alone is not a risk factor for admission to the ICU. As of March 25, ICU mortality was 26%. However, 58% were still in the ICU. Scary study, telling us a lot about the fragility of health care systems in even the wealthiest countries.
Wunsch H. The outbreak that invented intensive care. Nature, World View, April 3, 2020. Full-text: https://www.nature.com/articles/d41586-020-01019-y
Interesting article on Copenhagen’s polio epidemic in 1952, when over 300 patients (see below) developed respiratory paralysis within a few weeks, completely overwhelming the ventilator facilities. Does this remind you of something?
West JB. The physiological challenges of the 1952 Copenhagen poliomyelitis epidemic and a renaissance in clinical respiratory physiology. J Appl Physiol 2005 Aug;99(2):424-32. PubMed: https://pubmed.gov/16020437. Full-text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1351016/
Yes, it’s old. But, please, read this incredible story on hope and despair, on enormous medical challenges and true heroes, highly topical after almost 60 years. A comprehensive review about a forgotten epidemic occurring 1952 at the Belgdam Hospital in Copenhagen, Denmark: about 3,000 polio patients were admitted between August and December, among them 1,250 with paralysis and 345 with respiratory failure – due to bulbar or bulbospinal polio affecting brainstem or nerves that control breathing. The heroic solution was to recruit 1,500 medical and dental students, providing round-the-clock manual ventilation using rubber bags, with only the patient’s appearance to guide them. For a total of 165,000 hours. Think about it. The students were flying by sight. Sometimes, only the patients’ rolling back eyes signalled that more ventilation was needed. Watery eyes while reading this heartbreaking article. A perfect story for anti-vaxxers (if these damned trolls would take notice). And about how fast we forget!
Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility – King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 3;69(13):377-381. PubMed: https://pubmed.gov/32240128. Full-text: https://doi.org/10.15585/mmwr.mm6913e1
Outbreak in a long-term care facility: Test them all, immediately! Following identification of a case of SARS-CoV-2 in a health care worker, 13/23 residents who tested positive were asymptomatic or presymptomatic on the day of testing.
Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology. 2020 Apr 2. PubMed: https://pubmed.gov/32240279. Full-text: https://doi.org/10.4193/Rhin20.114
Case report and series on isolated sudden onset anosmia, urging to consider this presentation.
Back A, Tulsky JA, Arnold RM. Communication Skills in the Age of COVID-19. Ann Intern Med 2020, April 2. Full-text: https://doi.org/10.7326/M20-1376
Thoughts about how to communicate as a clinician in this crisis. Talking maps for communication tasks that none of us have faced before, including facilitating virtual goodbyes between family members and dying patients with restricted access. And explaining decisions on why a particular patient will not receive a scarce resource: “I can see how it feels unfair”. Phew. Could anyone ever have imagined that?
Wu P, Duan F, Luo C, et al. Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. Published online March 31, 2020. Full-text: https://doi.org/10.1001/jamaophthalmol.2020.1291
In a case series from China, 12/38 patients (32%, more common in severe COVID-19 cases) had ocular manifestations consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, or increased secretions. Two patients had positive PCR results from conjunctival swabs.
Bonow RO, Fonarow GC, O´Gara PT, Yancy CW. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiol. 2020 Mar 27. PubMed: https://pubmed.gov/32219362. Full-text: https://doi.org/10.1001/jamacardio.2020.1105
Brief review on the potential for direct and indirect adverse effects of SARS-CoV-2 on the heart and especially so in those with already established heart disease.
Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020; (published online March 30.) Full-text: https://doi.org/10.1016/S1473-3099(20)30243-7
Defining the case fatality rate (CFR) remains challenging and simply dividing the number of deaths by the number of cases can be misleading. Using individual-case data and after careful modelling, CFR was 1.38% (95% CI, 1.23–1.53) in this analysis. The mean duration from symptom onset to death was 17.8 days (95% 16.9–19.2).
Bhatraju PK, Ghassemieh BJ, Nichols M. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. NEJM March 30, 2020. Full-text: https://doi.org/10.1056/NEJMoa2004500
More than “Ok, COVID-19 has reached the US”: this paper describes in detail the demographic characteristics, coexisting conditions, imaging findings, and outcomes among 21 critically ill patients admitted at ICUs.
An older patient with COVID-19 and non-specific symptoms is described, as well as another case with heart failure, mimicking COVID-19. Both cases underline the need for extensive testing.
Chen G, Wu D, Guo W, et al. Clinical and immunologic features in severe and moderate Coronavirus Disease 2019. J Clin Invest. 2020 Mar 27. PubMed: https://pubmed.gov/32217835. Full-text: https://doi.org/137244
First study on immunologic characteristics of 21 patients (retrospective). Total lymphocytes but also CD4+ and CD8+ T cells decreased in nearly all patients, and were markedly lower in severe cases (294, 178 and 89 x 106/L) than moderate cases (641, 382 and 254 x 106/L). Immunological markers may be of importance due to their correlation with disease severity in COVID-19.