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New Year 2020
ProMed (International Society for Infectious Diseases). Undiagnosed pneumonia – China (HU): RFI. Archive Number: 20191230.6864153. Full-text: https://promedmail.org/promed-post/?id=6864153 ll
This email is the first message that alerted the world to what was to become the worst health crisis in 100 years.
Cyranoski D. New virus identified as likely cause of mystery illness in China. Nature (News). Full-text: https://www.nature.com/articles/d41586-020-00020-9 ll
The first news report in a major scientific journal. A day later, an updated version reports a new coronavirus as the likely cause of the pneumonia-like illness. The virus’s genome is sequenced.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. PubMed: https://pubmed.gov/31986264. Full-text: https://doi.org/10.1016/S0140-6736(20)30183-5 l (Important)
The first clinical paper about what would later be called COVID-19. The authors describe 41 patients with a median age of 49 years admitted by 2 January to Jin Yin-Tan Hospital (金银潭医院), Wuhan. Thirteen patients (32%) needed ICU care and 6 patients died (15%). The paper offers the first glimpse at laboratory prognostic markers.
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Feb 24. PubMed: https://pubmed.gov/32091533. Fulltext: https://doi.org/10.1001/jama.2020.2648 l (Important)
A bonanza of data at a fairly early stage of the pandemic – and shocking numbers at a moment when local epidemics were taking off in Europe. A must-read for everyone.
Spectrum of disease:
- Mild: 81%
- Severe: 14%
- Critical: 5%
- 14.8% in patients aged ≥ 80 years
- 8.0% in patients aged 70-79 years
* Summaries of the articles from
24 February until 27 March will be added soon. *
Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. PubMed: https://pubmed.gov/32109013. Full-text: https://doi.org/10.1056/NEJMoa2002032 ll (Outstanding)
Xia Y, Jin R, Zhao J, Li W, Shen H. Risk of COVID-19 for patients with cancer. Lancet Oncol. 2020 Apr;21(4):e180. PubMed: https://pubmed.gov/32142622. Full-text: https://doi.org/10.1016/S1470-2045(20)30150-9
Hong H, Wang Y, Chung HT, Chen CJ. Clinical characteristics of novel coronavirus disease 2019 (COVID-19) in newborns, infants and children. Pediatr Neonatol. 2020 Mar 10. PubMed: https://pubmed.gov/32199864. Fulltext: https://doi.org/10.1016/j.pedneo.2020.03.001
Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13:e200994. PubMed: https://pubmed.gov/32167524. Full-text: https://doi.org/10.1001/jamainternmed.2020.0994
Wang Y, Liu Y, Liu L, Wang X, Luo N, Li L. Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China. J Infect Dis. 2020 May 11;221(11):1770-1774. PubMed: https://pubmed.gov/32179910. Full-text: https://doi.org/10.1093/infdis/jiaa119
Wu JT, Leung K, Bushman M, et al. Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China. Nat Med. 2020 Apr;26(4):506-510. PubMed: https://pubmed.gov/32284616. Full-text: https://doi.org/10.1038/s41591-020-0822-7 l (Important)
Clerkin KJ, Fried JA, Raikhelkar J, et al. COVID-19 and Cardiovascular Disease. Circulation. 2020 May 19;141(20):1648-1655. PubMed: https://pubmed.gov/32200663. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.046941
Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 2020 Mar;25(10):2000180. PubMed: https://pubmed.gov/32183930. Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.10.2000180 l (Important)
Poston JT, Patel BK, Davis AM. Management of Critically Ill Adults With COVID-19. JAMA. 2020 Mar 26. PubMed: https://pubmed.gov/32215647. Full-text: https://doi.org/10.1001/jama.2020.4914
Daily Top 10
Fauci AS, Lane HC, Redfield RR. Covid-19 – Navigating the Uncharted. N Engl J Med. 2020 Mar 26;382(13):1268-1269. PubMed: https://pubmed.gov/32109011. Full-text: https://doi.org/10.1056/NEJMe2002387
Brief overview of current research topics from opinion leaders.
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.
Risk factors, comorbidities
McMichael TM, Currie DW, Clark S, et al. Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington. N Engl J Med. 2020 Mar 27. PubMed: https://pubmed.gov/32220208. Full-text: https://doi.org/10.1056/NEJMoa2005412 l (Important)
Important paper that highlights the severity of COVID-19 in older people. A total of 167 confirmed cases affecting 101 residents in a long-term care facility, 50 health care personnel (HCP), and 16 visitors. The case fatality rate for residents was 33.7% (34 of 101) and 0% among HCP.
Guan WJ, Liang WH, Zhao Y, et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis. Eur Respir J. 2020 Mar 26. PubMed: https://pubmed.gov/32217650. Full-text: https://doi.org/10.1183/13993003.00547-2020 l (Important)
More on the role of comorbidities. 1,590 hospitalised patients from 575 hospitals across mainland China. After adjusting for age and smoking status, COPD [hazards ratio (HR) 2.681, 95% confidence interval (95%CI) 1.424-5.048], diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were risk factors of reaching endpoints.
Inciardi RM, Lupi L, Zaccone G, et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 Mar 27. PubMed: https://pubmed.gov/32219357. Full-text: https://doi.org/10.1001/jamacardio.2020.1096
Interesting case report on myopericarditis with systolic dysfunction which highlights cardiac involvement as a complication, even without symptoms and signs of interstitial pneumonia.
Kutikov A, Weinberg DS, Edelman MJ, Horwitz EM, Uzzo RG, Fisher RI. A War on Two Fronts: Cancer Care in the Time of COVID-19. Ann Intern Med. 2020 Mar 27. PubMed: https://pubmed.gov/32219410. Full-text: https://doi.org/10.7326/M20-1133
Inspiring thoughts on treatment and care for patients with cancer. No new data.
Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091. PubMed: https://pubmed.gov/32217556. Full-text: https://doi.org/10.1136/bmj.m1091
Retrospective case series of 113 deceased patients. The median time from disease onset to death was 16 (IQR 12.0-20.0) days. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (100%), type I respiratory failure (51%), sepsis (100%), acute cardiac injury (77%), heart failure (49%), alkalosis (40%), hyperkalemia (37%), acute kidney injury (25%), and hypoxic encephalopathy (20%).
Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020 Mar 27;368:m1185. PubMed: https://pubmed.gov/32220865. Full-text: https://doi.org/10.1136/bmj.m1185
Discussion of a possible link between NSAIDs and both respiratory and cardiovascular adverse effects in COVID-19. Recommends pragmatic approach: regular NSAID use should probably not be recommended first line.
Vaduganathan M, Vardeny O, Michel T, McMurray JV, Pfeffer MA, Solomon SD. Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. NEJM, March 30, 2020. Fulltext: https://www.nejm.org/doi/full/10.1056/NEJMsr2005760?
Fantastic review of an interdisciplinary expert panel on the use, risks and benefit of RAAS inhibitors (ACE inhibitors and sartans) in the COVID-19 era. Bottom line: We don’t know enough. Until further data are available, RAAS inhibitors can be continued.
Joob B, Wiwanitkit V. SARS-CoV-2 and HIV. J Med Virol. 2020 Mar 27. PubMed: https://pubmed.gov/32220066. Fulltext: https://doi.org/10.1002/jmv.25782
A few new thoughts on HIV infection and COVID-19.
Zhu F, Cao Y, Xu S, Zhou M. Co-infection of SARS-CoV-2 and HIV in a patient in Wuhan city, China [published online ahead of print March 11, 2020]. J Med Virol. https://doi.org/10.1002/jmv.25732
First case report of patient with undiagnosed HIV infection (low CD4 counts), recovering from a coronavirus–related pneumonia. Argues against deleterious effect of HIV.
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.
Nickel CH, Bingisser R. Mimics and chameleons of COVID-19. Swiss Med Wkly. 2020 Mar 23;150:w20231. PubMed: https://pubmed.gov/32202647. https://doi.org/10.4414/smw.2020.20231
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.
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).
Yao H, Chen JH, Xu YF. Patients with mental health disorders in the COVID-19 epidemic. Lancet Psychiatry. 2020 Apr;7(4):e21. Full-text: https://doi.org/10.1016/S2215-0366(20)30090-0
Don’t forget people with mental health conditions! A few thoughts on these patients who could be more substantially affected, resulting in relapses or worsening of an already existing mental health condition because of high susceptibility to stress compared with the general population.
Chen Q, Liang M, Li Y, et al. Mental health care for medical staff in China during the COVID-19 outbreak. Lancet Psychiatry. 2020 Apr;7(4):e15-e16. PubMed: https://pubmed.gov/32085839. Full-text: https://doi.org/10.1016/S2215-0366(20)30078-X
And don’t forget the staff! Some thoughts on how to maintain staff mental health during such a crisis.
Jin XH, Zheng KI, Pan KH, Xie YP, Zheng MH. COVID-19 in a patient with chronic lymphocytic leukaemia. Lancet Haematol. 2020 Apr;7(4):e351-e352. Full-text: https://doi.org/10.1016/S2352-3026(20)30074-0
Interesting case report on a patient with CLL. Clinical and biochemical features of COVID-19 might be partly masked by coexisting CLL. Longer incubation period was presumed.
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.
Kaiser UB, Mirmira RG, Stewart PM. Our Response to COVID-19 as Endocrinologists and Diabetologists. J Clin Endocrin Metabol, 105, May 2020, published 31 March 2020, dgaa148, https://doi.org/10.1210/clinem/dgaa148
Thoughts on diabetes management, glucocorticoid use, pituitary or other neuroendocrine diseases.
CDC COVID-19 Response Team. Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020. MMWR Morb Mortal Wkly Rep. ePub: 31 March 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6913e2
No, the situation in the US does not differ from other countries. Among 7,162 patients with underlying health conditions or potential risk factors reported to the CDC, those with these conditions were more likely admitted to the hospital and to an ICU. And yes, “persons with underlying health conditions who have symptoms of COVID-19 should immediately contact their health care provider”.
Bousquet J, Akdis C, Jutel M, et al. Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement. Allergy. 2020 Mar 31. PubMed: https://pubmed.gov/32233040. Full-text: https://doi.org/10.1111/all.14302
A joint statement of the European Academy of Allergology and Clinical Immunology, following the results of a questionnaire. Bottom line: Stopping intranasal steroids is not advised, until we know better.
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?
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.
Meng J, Xiao G, Zhang J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020 Dec;9(1):757-760. PubMed: https://pubmed.gov/32228222. Full-text: https://doi.org/10.1080/22221751.2020.1746200
First study arguing against any deleterious effect of RAAS inhibitors (ACE inhibitors or sartans) in COVID-19! Among 42 of 417 patients admitted to Shenzhen Hospital while on antihypertensive therapy, those receiving RAAS inhibitors had a lower rate of severe diseases than patients without (5/17 compared to 12/25) and a trend toward a lower level of IL-6 in peripheral blood.
The Lancet Oncology. COVID-19: global consequences for oncology. Lancet Oncol. 2020 Apr;21(4):467. PubMed: https://pubmed.gov/32240603. Full-text: https://doi.org/10.1016/S1470-2045(20)30175-3
Thoughts on how the pandemic affects treatment of patients with cancer and how it will hit the wider oncology community. Substantial changes for research, education, and collaboration are expected, including reduced international travel and increased remote networking and telemedicine.
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.
Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers. JAMA Cardiol. 2020 Apr 3. PubMed: https://pubmed.gov/32242890. Full-text: https://doi.org/10.1001/jamacardio.2020.1282
This mini-review outlines the mechanisms by which RAAS inhibitors (ACEIs/ARBs) may be of benefit in COVID-19. Overview of the current recommendations for their use in infected patients. According to the authors, the biological plausibility of the salutary effects of RAAS inhibitors is intriguing and several trials of starting losartan in patients with COVID-19 are currently being planned.
Al-Shamsi HO, Alhazzani W, Alhuraiji A, et al. A Practical Approach to the Management of Cancer Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic: An International Collaborative Group. Oncologist. 2020 Apr 3. PubMed: https://pubmed.gov/32243668. Full-text: https://doi.org/10.1634/theoncologist.2020-0213
Detailed and important review for oncologists, addressing current challenges associated with managing cancer patients during theCOVID-19 pandemic.
Volkow ND. Collision of the COVID-19 and Addiction Epidemics. Ann Intern Med. 2020 Apr 2. PubMed: https://pubmed.gov/32240293. Full-text: https://doi.org/10.7326/M20-1212
Don’t forget or marginalize persons with substance use disorders during this crisis!
Fried JA, Ramasubbu K, Bhatt R, et al. The Variety of Cardiovascular Presentations of COVID-19. Circulation. 2020 Apr 3. PubMed: https://pubmed.gov/32243205. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047164
Four COVID-19 cases with cardiovascular presentations are described. In patients presenting with what appears to be a typical cardiac syndrome, COVID-19 infection should be in the differential during the current pandemic, even in the absence of fever or cough.
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!
Omer SB, Malani P, Del Rio C. The COVID-19 Pandemic in the US: A Clinical Update. JAMA. 2020 Apr 6. PubMed: https://pubmed.gov/32250388. Full-text: https://doi.org/10.1001/jama.2020.5788
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?
Schiffrin EL, Flack J, Ito S, Muntner P, Webb C. Hypertension and COVID-19. Am J Hypertens. 2020 Apr 6. PubMed: https://pubmed.gov/32251498. Full-text: https://doi.org/10.1093/ajh/hpaa057
Is hypertension a true risk factor for severe COVID-19 courses? According to the authors, there is as yet (March 29) “no evidence” that hypertension is related to outcomes of COVID-19, or that ACE inhibitor or ARB use is harmful, or for that matter beneficial.
Pasha SB, Fatima H, Ghouri YA. Management of Inflammatory Bowel Diseases in the Wake of COVID-19 Pandemic. J Gastroenterol Hepatol. 2020 Apr 4. PubMed: https://pubmed.gov/32246874. Full-text: https://doi.org/10.1111/jgh.15056
Some thoughts on how to manage patients suffering from Inflammatory Bowel Diseases, regarding their ongoing immunosuppressive therapies which could render them more susceptible to acquire COVID-19 infection and develop severe courses.
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.
Dave M, Seoudi N, Coulthard P. Urgent dental care for patients during the COVID-19 pandemic. Lancet. 2020 Apr 3. PubMed: https://pubmed.gov/32251619. Full-text: https://doi.org/10.1016/S0140-6736(20)30806-0
Don’t forget the dentists! And test them with the same high priority as that of medical healthcare workers in hospitals!
Sun J, Aghemo A, Forner A, Valenti L. COVID-19 and liver disease. Liver Int. 2020 Apr 6. doi: https://doi.org/10.1111/liv.14470. [Epub ahead of print]
“Since December 2019, patients with unexplained pneumonia have been found in Wuhan, Hubei Province, China, which was caused by a novel coronavirus that had not been previously identified (1). Tentatively defined as 2019 novel coronavirus (2019-nCoV), the pathogen has now been named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) (2), while the disease termed Coronavirus Disease 2019 (COVID-19).” This abstract was published on April 6, with references. In all seriousness. Come on guys, we all know that already! Is it to be feared that nobody will read your interesting mini-review on mechanisms and clinical implications of liver injury, unmet clinical needs and main research questions?
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.
Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther. 2020 Apr 7. PubMed: https://pubmed.gov/32266761. Full-text: https://doi.org/10.1111/cns.13372
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.
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.
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.
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.
Torres T, Puig L. Managing Cutaneous Immune-Mediated Diseases During the COVID-19 Pandemic. Am J Clin Dermatol. 2020 Apr 10. PubMed: https://pubmed.gov/32277351. Full-text: https://doi.org/10.1007/s40257-020-00514-2
Patients with cutaneous immune-mediated diseases (including psoriasis, atopic dermatitis, and hidradenitis suppurativa) may continue their treatment even during the COVID-19 outbreak, preventing disease flares. However, in patients with active COVID-19 infection, it is generally recommended to withhold immunosuppressive or biologic treatment.
Coles CE, Aristei C, Bliss J, et al. International Guidelines on Radiation Therapy for Breast Cancer During the COVID-19 Pandemic. Clin Oncol (R Coll Radiol). 2020 May;32(5):279-281. PubMed: https://pubmed.gov/32241520. Full-text: https://doi.org/10.1016/j.clon.2020.03.006
In order to reduce hospital visits to a minimum and to ease pressure on workforce, detailed guidelines on radiation therapy for breast cancer are given, mainly focussing on hypofractionation.
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.
Wang H, Li T, Barbarino P, et al. Dementia care during COVID-19. Lancet. 2020 Apr 11; 395(10231):1190-1191. PubMed: https://pubmed.gov/32240625. Full-text: https://doi.org/10.1016/S0140-6736(20)30755-8
Some thoughts on dementia care in this crisis.
Daniels MJ, Cohen MG, Bavry AA, Kumbhani DJ. Reperfusion of STEMI in the COVID-19 Era – Business as Usual? Circulation. 2020 Apr 13. PubMed: https://pubmed.gov/32282225. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047122
In the current crisis with limited resources to protect the work force, fibrinolytic therapy (FT) may be considered for patients with myocardial infarction (STEMI). FT may even be preferred over primary percutaneous coronary intervention. Arguments for this strategy are summarized.
Zhong Z, Zhang Q, Xia H, et al. Clinical characteristics and immunosuppressants management of coronavirus disease 2019 in solid organ transplant recipients. Am J Transplant. 2020 Apr 13. PubMed: https://pubmed.gov/32282986. Full-text: https://doi.org/10.1111/ajt.15928
COVID-19 was observed in two transplant recipients (liver and kidney), with different treatments and prognoses. Both patients recovered.
Zhan M, Qin Y, Xue X, Zhu S. Death from Covid-19 of 23 Health Care Workers in China. N Engl J Med. 2020 Apr 15. PubMed: https://pubmed.gov/32294342. Full-text: https://doi.org/10.1056/NEJMc2005696
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.
Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol. 2020 Apr 15. PubMed: https://pubmed.gov/32296910. Full-text: https://doi.org/10.1007/s00277-020-04019-0
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.
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.
Helms J, Kremer S, Merdji H, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020 Apr 15. PubMed: https://pubmed.gov/32294339. Full-text: https://doi.org/10.1056/NEJMc2008597
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.
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.
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.
Brojakowska A, Narula J, Shimony R, Bander J. Clinical Implications of SARS-Cov2 Interaction with Renin Angiotensin System. J Am Coll Cardiol. 2020 Apr 14. PubMed: https://pubmed.gov/32305401. Full-text: https://doi.org/10.1016/j.jacc.2020.04.028
Don’t stop your sartans or ACE inhibitors! The authors hypothesize that the benefits of treatment with renin-angiotensin system inhibitors in SARS-COV-2 may outweigh the risks and at the very least should not be withheld.
Kennedy NA, Jones GR, Lamb CA, et al. British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic. Gut. 2020 Apr 17. PubMed: https://pubmed.gov/32303607. Full-text: https://doi.org/10.1136/gutjnl-2020-321244
Making recommendations in the absence of data is not that easy. The authors have made heroic attempts to balance the risk of immune modifying drugs with the risk associated with active disease.
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.
Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020 Jun 1;217(6). PubMed: https://pubmed.gov/32302401. Full-text: https://doi.org/10.1084/jem.20200652
Case report of a patient who succumbed to COVID-19. Hypothesis that a powerful function of neutrophils – the ability to form neutrophil extracellular traps (NETs) – may contribute to organ damage and mortality in COVID-19. Targeting NETs directly and/or indirectly with existing drugs may reduce clinical severity.
Spiezia L, Boscolo A, Poletto F, et al. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure. Thromb Haemost. 2020 Apr 21. PubMed: https://pubmed.gov/32316063. Full-text: https://doi.org/10.1055/s-0040-1710018
Case series of 22 patients with acute respiratory failure present a severe hypercoagulability rather than consumptive coagulopathy. Fibrin formation and polymerization may predispose to thrombosis and correlate with a worse outcome.
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%).
Finsterer J, Stollberger C. Causes of hypogeusia/hyposmia in SARS-CoV2 infected patients. J Med Virol. 2020 Apr 20. PubMed: https://pubmed.gov/32311107. Full-text: https://doi.org/10.1002/jmv.25903
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.
Sattar N, McInnes IB, McMurray JJV. Obesity a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms. Circulation. 2020 Apr 22. PubMed: https://pubmed.gov/32320270. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047659
Brief review on obesity as a unifying risk factor for severe COVID-19 infection, reducing both protective cardiorespiratory reserve as well as potentiating the immune dysregulation. Possible patho-mechanisms are discussed.
Caputo ND, Strayer RJ, Levitan R. Early Self-Proning in Awake, Non-intubated Patients in the Emergency Department: A Single ED´s Experience during the COVID-19 Pandemic. Acad Emerg Med. 2020 Apr 22. PubMed: https://pubmed.gov/32320506. Full-text: https://doi.org/10.1111/acem.13994
Proning helps, even in awake, non-intubated patients. Among 50 patients, the median SpO2 at triage was 80%. After application of supplemental oxygen was given to patients on room air it was 84%. After 5 minutes of proning was added, SpO2 improved to 94%.
Sriram K, Insel PA. Risks of ACE inhibitor and ARB usage in COVID-19: evaluating the evidence. Clin Pharmacol Ther. 2020 Apr 22. PubMed: https://pubmed.gov/32320478. Full-text: https://doi.org/10.1002/cpt.1863
Nice review. Data from 12 animal studies and from 12 human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. The authors conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.
Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020 Apr 17. PubMed: https://pubmed.gov/32302265. Full-text: https://doi.org/10.1161/CIRCRESAHA.120.317134
Same idea: in this retrospective, multi-center study of 1128 adult patients with hypertension diagnosed with COVID-19, 188 patients taking ACEI/ARB were compared with 940 patients without using ACEI/ARB. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%). In a Cox model, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group (adjusted HR 0.42; 95%CI, 0.19-0.92).
Pereira MR, Mohan S, Cohen DJ, et al. COVID-19 in Solid Organ Transplant Recipients: Initial Report from the US Epicenter. Am J Transplant. 2020 Apr 24. PubMed: https://pubmed.gov/32330343. Full-text: https://doi.org/10.1111/ajt.15941
The first large cohort of COVID-19 in transplant recipients. Of 90 patients (median age 57 years), 46 were kidney recipients, 17 lung, 13 liver, 9 heart and 5 dual-organ transplants. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU), indicating that transplant recipients appear to have more severe outcomes.
Akalin E, Azzi Y, Bartash B. Covid-19 and Kidney Transplantation. N Engl J Med. 2020 Apr 24. PubMed: https://pubmed.gov/32329975. Full-text: https://doi.org/10.1056/NEJMc2011117
Single center experience with 36 kidney transplant recipients. Patients appear to have less fever as an initial symptom, lower CD3/4/8 cell counts and more rapid clinical progression: after 21 days, 10 died.
French JA, Brodie MJ, Caraballo R, et al. Keeping people with epilepsy safe during the Covid-19 pandemic. Neurology. 2020 Apr 23. PubMed: https://pubmed.gov/32327490. Full-text: https://doi.org/10.1212/WNL.0000000000009632
Some helpful recommendations on how to modify clinical care for people with epilepsy and what general advice can be given to these patients during this crisis.
Cai G, Bosse Y, Xiao F, Kheradmand F, Amos CI. Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020 Apr 24. PubMed: https://pubmed.gov/32329629. Full-text: https://doi.org/10.1164/rccm.202003-0693LE
Brand new information: smoking is not the best idea. However, this is particularly true in the current pandemic. Ever having smoked significantly and substantially increased pulmonary ACE2 expression by 25%. The significant smoking effect on ACE2 pulmonary expression may suggest an increased risk for viral binding and entry of SARS-CoV-2 in lungs of smokers.
Wadman M, Couzin-Frankel J, Kaiser J, et al. A rampage through the body. Science 24 Apr 2020: Vol. 368, Issue 6489, pp. 356-360. Full-text: https://science.sciencemag.org/content/368/6489/356 l (Important)
Is there anybody still twaddling about herd immunity? Let him read this detailed feature, describing the map of the devastation that COVID-19 can inflict not only on the lungs but on other organs as well, including blood vessels, heart, brain, kidneys and other organs. Scientists are just beginning to probe the nature of that harm.
Servick K. Survivors’ burden. Science 24 Apr 2020: Vol. 368, Issue 6489, pp. 359. https://science.sciencemag.org/content/368/6489/359
Discharge from ICU is not the end of it. Clinicians are now turning their attention to potential lingering effects of both the virus and the emergency treatments that allow people to survive. Scarring can cause long-term breathing problems. This article also discusses other topics of concern such as muscle atrophy and weakness, mental problems but also cognitive impairment after leaving long-term intensive care.
Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. 2020 Apr 24. PubMed: https://pubmed.gov/32329799. Full-text: https://doi.org/10.1001/jama.2020.6825
Useful review on the unique lung injury induced by SARS-CoV-2 infection. It has become clear that acute respiratory distress syndrome (ARDS) in COVID-19 is different from ARDS. “CARDs” appears to include an important vascular insult that potentially mandates a different treatment approach than customarily applied for ARDS. The authors review their experiences and propose to categorize patients. In type L (low lung elastance, high compliance, low response to PEEP), infiltrates are often limited in extent and initially characterized by a ground-glass pattern on CT that signifies interstitial rather than alveolar edema. Many patients do not appear overtly dyspneic and may stabilize at this stage without deterioration. Others may transit to a clinical picture more characteristic of typical ARDS: Type H shows extensive CT consolidations, high elastance (low compliance) and high PEEP response. Clearly, types L and H are the conceptual extremes of a spectrum that includes intermediate stages.
Poissy J, Goutay J, Caplan M, et al. Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence. Circulation. 2020 Apr 24. PubMed: https://pubmed.gov/32330083. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047430
Case series from Lille, France showing a high prevalence of Pulmonary Embolism (PE) in severe COVID-19. Among the first 107 COVID-19 patients admitted to the ICU for pneumonia in March, the authors identified 22 (20.6%) cases. It is of note that at the time of diagnosis of PE, 20/22 were receiving prophylactic antithrombotic treatment (UFH or LWMH) according to the current guidelines in critically ill patients.
Matheny Antommaria AH, Gibb TS, McGuire AL, et al. Ventilator Triage Policies During the COVID-19 Pandemic at U.S. Hospitals Associated With Members of the Association of Bioethics Program Directors. Ann Intern Med. 2020 Apr 24. PubMed: https://pubmed.gov/32330224. Full-text: https://doi.org/10.7326/M20-1738
Triage? Nobody is prepared, according to this survey among 67 Bioethics Program Directors from North American hospitals. Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation. Of note, among the most frequently cited triage criteria was “lottery” (35%). Great.
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.
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.
De Filippo O, D’Ascenzo F, Angelini F, et al. Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy. N Engl J Med, April 28, 2020. Full-text: https://doi.org/10.1056/NEJMc2009166
The authors report a significant decrease in acute coronary syndrome-related hospitalization rates across several cardiovascular centers in northern Italy during the early days of the outbreak.
Castiglion V, Chiriacò M, Emdin M, et al. Statin therapy in COVID-19 infection. European Heart Journal Cardiovascular Pharmacotherapy, 2020, 29 April. Full-text: https://doi.org/10.1093/ehjcvp/pvaa042
Brief review: adjuvant treatment and continuation of pre-existing statin therapy could improve the clinical course of patients with COVID-19, either by their immunomodulatory action or by preventing cardiovascular damage.
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.
Haberman R, Axelrad J, Chen A, et al. Covid-19 in Immune-Mediated Inflammatory Diseases – Case Series from New York. N Engl J Med. 2020 Apr 29. PubMed: https://pubmed.gov/32348641. Full-text: https://doi.org/10.1056/NEJMc2009567
Baseline use of biologics is not associated with worse COVID-19 outcomes. A case series of 86 patients with immune-mediated inflammatory disease (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, or related conditions) and symptomatic COVID-19, among them 62 (72%) receiving biologics or Janus kinase (JAK) inhibitors. The percentage of patients who were receiving biologics or JAK inhibitors at baseline was higher among the ambulatory patients than among the hospitalized patients. In contrast, hospitalization rates were higher in patients treated with oral glucocorticoids, hydroxychloroquine and methotrexate.
Rangé G, Hakim R, Motreff P. Where have the STEMIs gone during COVID-19 lockdown? European Heart Journal – Quality of Care and Clinical Outcomes, April 29, 2020. Full-text: https://doi.org/10.1093/ehjqcco/qcaa034
Best paper title of the day. Using a French Registry, the authors found a spectacular drop of 25% for admission due to STEMI between March 2019 and March 2020. The steep decline was found for both acute (< 24hrs) and late presentation (> 24 hrs) STEMI. But where did they go? According to the authors, explanations may be patients’ fear of coming to the hospital or disturbing busy caregivers, especially in the case of mild STEMI clinical presentation. Other hypothetical reasons are reduced air pollution, better adherence to treatment, limited physical activity or absence of occupational stress during lockdown. When will we ever learn?
Baldi E, Sechi GM, Mare C, et al. Out-of-Hospital Cardiac Arrest during the Covid-19 Outbreak in Italy. N Engl J Med. 2020 Apr 29. PubMed: https://pubmed.gov/32348640. Full-text: https://doi.org/10.1056/NEJMc2010418
Avoiding hospitals, staying at home, dying of fear? Using data from the Lombardy Cardiac Arrest Registry for the provinces of Lodi, Cremona, Pavia, and Mantua during the first 40 days of the COVID-19 outbreak (February 21 through March 31, 2020), the authors found a 58% increase of out-of-hospital cardiac arrest compared to the same period in 2019.
Ziehr DR, Alladina J, Petri CR, et al. Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study. Am J Respir Crit Care Med. 2020 Apr 29. PubMed: https://pubmed.gov/32348678. Full-text: https://doi.org/10.1164/rccm.202004-1163LE
Treat it like ARDS! The authors provide a pathophysiologic justification for the use of established ARDS therapies, including low tidal volume and early prone ventilation. In their retrospective cohort of 66 COVID-19 patients (median age 58 years) with respiratory failure, fatality was only 17%. The authors conclude that their patients exhibit similar gas exchange, respiratory system mechanics, and response to prone ventilation as prior large cohorts of patients with ARDS.
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.
Stefanini GG, Montorfano M, Trabattoni D, et al. ST-Elevation Myocardial Infarction in Patients with COVID-19: Clinical and Angiographic Outcomes. Circulation. 2020 Apr 30. PubMed: https://pubmed.gov/32352306. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047525
STEMI may represent the first clinical manifestation of COVID-19. In 11 out of 28 patients (39%) with STEMI, a culprit lesion was not identifiable by coronary angiography. According to the authors, a dedicated diagnostic pathway should be delineated for COVID-19 patients with STEMI, aimed at minimizing patients’ procedural risks and healthcare providers’ risk of infection.
Yang G, Tan Z, Zhou L, et al. Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study. Hypertension. 2020 Apr 29. PubMed: https://pubmed.gov/32348166. Full-text: https://doi.org/10.1161/HYPERTENSIONAHA.120.15143
The next retrospective study analysing COVID-19 patients with hypertension, argueing against deleterious effects of angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors. Patients on these drugs (n=43) had significantly lower concentrations of CRP (p = 0.049) and procalcitonin (p = 0.008) than patients on other antihypertensive drugs (n = 83). Furthermore, trends toward lower proportions of critical diseases (9.3% vs 22.9%; p = 0.061) and death rates (4.7% vs 13.3%; p = 0.216) were observed.
This has been the week of the dermatologists: numerous studies reported on cutaneous manifestations seen in the context of COVID-19. The most prominent phenomenon, the so-called “COVID toes”, are chilblain-like lesions which mainly occur at acral areas [chilblain: Frostbeule (de), engelure (fr), sabañón (es), gelone (it), frieira (pt), 冻疮 (cn)]. These lesions can be painful (sometimes itchy, sometimes asymptomatic) and may represent the only symptom or late manifestations of SARS-CoV-2 infection. Of note, in most patients with “COVID toes” the disease is only mild to moderate. It is speculated that the lesions are caused by inflammation in the walls of blood vessels, or by small micro-clots in the blood. However, whether “COVID toes” represent a coagulation disorder or a hypersensitivity reaction is still unknown. In addition, in many patients, SARS-CoV-2 PCR was negative (or not done) and serology tests (to prove the relationship) are still pending.
Fernandez-Nieto D, Jimenez-Cauhe J, Suarez-Valle A, et al. Characterization of acute acro-ischemic lesions in non-hospitalized patients: a case series of 132 patients during the COVID-19 outbreak. J Am Acad Dermatol. 2020 Apr 24. PubMed: https://pubmed.gov/32339703. Full-text: https://doi.org/10.1016/j.jaad.2020.04.093
Authors describe two different patterns of acute acro-ischemic lesions, which can overlap. The chilblain-like pattern was present in 95 patients (72.0%). It is characterized by red to violet macules, plaques and nodules, usually at the distal aspects of toes and fingers. The erythema multiforme-like pattern was present in 37 patients (28.0%).
Galvan Casas C, Catala A, Carretero Hernandez G, et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020 Apr 29. PubMed: https://pubmed.gov/32348545. Full-text: https://doi.org/10.1111/bjd.19163 l (Important)
The authors describe five clinical cutaneous manifestations of lesions: acral areas of erythema with vesicles or pustules (pseudo-chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo-chilblain pattern frequently appears late in the evolution of the COVID-19 disease (59% after other symptoms).
Piccolo V, Neri I, Filippeschi C, et al. Chilblain-like lesions during COVID-19 epidemic: a preliminary study on 63 patients. J Eur Acad Dermatol Venereol. 2020 Apr 24. PubMed: https://pubmed.gov/32330334. Full-text: https://doi.org/10.1111/jdv.16526
Preliminary results of a survey among Italian dermatologists and pediatrics, reporting on 63 cases (only a few patients with confirmed COVID-19).
Recalcati S, Barbagallo T, Frasin LA, et al. Acral cutaneous lesions in the Time of COVID-19. J Eur Acad Dermatol Venereol. 2020 Apr 24. PubMed: https://pubmed.gov/32330324. Full-text: https://doi.org/10.1111/jdv.16533
A dermatology unit in Italy reports on 14 cases including 11 children. Lesions were localized on the feet in 8 cases, on the hands in 4 cases, on both sites in 2.
Duong TA, Velter C, Rybojad M, et al. Did Whatsapp reveal a new cutaneous COVID-19 manifestation? J Eur Acad Dermatol Venereol. 2020 Apr 24. PubMed: https://pubmed.gov/32330322. Full-text: https://doi.org/10.1111/jdv.16534
In a Whatsapp group of 400 French dermatologists, a total of 295 atypical skin eruptions or lesions of suspected or confirmed COVID-19 patients were posted between March 14 and April 10. Chilblains or chilblain-like lesions represented 146 posts, and 149 posts included other suspected COVID-19-related skin eruption, e.g. urticaria, rash, chickenpox-like or pityriasis rosea.
Marzano AV, Genovese G, Fabbrocini G, et al. Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients. J Am Acad Dermatol. 2020 Apr 16. PubMed: https://pubmed.gov/32305439. Full-text: https://doi.org/10.1016/j.jaad.2020.04.044
Case series on 22 adult patients with varicella-like lesions. Typical features were constant trunk involvement, usually scattered distribution and mild/absent pruritus, the latter being in line with most viral exanthems but unlike true varicella. Lesions generally appeared 3 days after systemic symptoms and disappeared by 8 days.
Sanchez A, Sohier P, Benghanem S, et al. Digitate Papulosquamous Eruption Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. JAMA Dermatol. 2020 Apr 30. PubMed: https://pubmed.gov/32352486. Full-text: https://doi.org/10.1001/jamadermatol.2020.1704
Case report on digitate papulosquamous eruption in a patient with severe COVID-19. This paraviral dermatosis could be a secondary result of the immune response against the virus.
Diaz-Guimaraens B, Dominguez-Santas M, Suarez-Valle A, et al. Petechial Skin Rash Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. JAMA Dermatol. 2020 Apr 30. PubMed: https://pubmed.gov/32352487. Full-text: https://doi.org/10.1001/jamadermatol.2020.1741
And yes, of course, rash may also occur. A case report with petechial skin rash with striking absence of lesions in the crural folds.
Quintana-Castanedo L, Feito-Rodriguez M, Valero-Lopez I, Chiloeches-Fernandez C, Sendagorta-Cudos E, Herranz-Pinto P. Urticarial exanthem as early diagnostic clue for COVID-19 infection. JAAD Case Rep. 2020 Apr 29. PubMed: https://pubmed.gov/32352022. Full-text: https://doi.org/10.1016/j.jdcr.2020.04.026
Another patient with impressive rash (a 61-year-old Spanish medical doctor).
Madigan LM, Micheletti RG, Shinkai K. How Dermatologists Can Learn and Contribute at the Leading Edge of the COVID-19 Global Pandemic. JAMA Dermatol. 2020 Apr 30. PubMed: https://pubmed.gov/32352485. Full-text: https://doi.org/10.1001/jamadermatol.2020.1438
A word of caution. Not all rashes or cutaneous manifestations seen in patients with COVID-19 can be attributed to the virus. Coinfections or medical complications have to be considered. Comprehensive mucocutaneous examinations, analysis of other systemic clinical features or host characteristics, and histopathologic correlation, will be vital to understanding the pathophysiologic mechanisms of what we are seeing on the skin.
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.
Zhu L, She ZG, Cheng X. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metabolism, April 30, 2020. Full-text: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30238-2 l (Important)
Check your HbA1c! The hitherto largest retrospective study on the impact of type 2 diabetes (T2D) has carefully analyzed 7,337 cases of COVID-19 in Hubei Province, China, among them 952 with pre-existing T2D. The authors found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio, 1.49) and multiple organ injury than the non-diabetic individuals. Well-controlled blood glucose was associated with markedly lower mortality (in-hospital death rate 1.1% versus 11.0%) compared to individuals with poorly controlled BG.
Piccolo R, Bruzzese D, Mauro C, et al. Population Trends in Rates of Percutaneous Coronary Revascularization for Acute Coronary Syndromes Associated with the COVID-19 Outbreak. Circulation. 2020 Apr 30. PubMed: https://pubmed.gov/32352318. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047457
Collateral damage of the current pandemic: data from Italy providing evidence that the outbreak of COVID-19 was associated with a decline by 32% in the number of percutaneous coronary intervention for acute coronary syndromes.
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.
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.
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.
Thornton J. Covid-19: the challenge of patient rehabilitation after intensive care. BMJ. 2020 May 6;369:m1787. PubMed: https://pubmed.gov/32376670. Full-text: https://doi.org/10.1136/bmj.m1787
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.
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Kawasaki-like syndrome in children (March/April 2020)
A new twist in this new pandemic: at the end of March 2020, Jones et al. described the case of a six-month-old baby girl with fever, rash and swelling characteristic of a rare pediatric inflammatory condition, Kawasaki syndrome (Jones 2020). The child is treated according to treatment guidelines with a single dose of 2g/kg intravenous immunoglobulin and high dose acetylsalicylic 20mg/kg four times daily. The fever breaks within hours.
A month later, on 27 April, the National Health Service (NHS) sends an email alert to members of the British Paediatric Critical Care Society (PICS) highlighting “a small rise in the number of cases of critically ill children presenting with an unusual clinical picture.” Many of these children have tested positive for COVID-19, while some had not. The alert indicates that “the cases have in common overlapping features of toxic shock syndrome and atypical Kawasaki disease with blood parameters consistent with severe COVID-19 in children. Abdominal pain and gastrointestinal symptoms have been a common feature as has cardiac inflammation”, (see the PICS statement).
A few days later, Sylvain Renolleau, head of the intensive care unit at Necker hospital, Paris, reports more than 20 children and adolescents 3 to 17 years old hospitalized in intensive care. The first cases were seen around 15 April. Symptoms included abdominal pain, diarrhea and vomiting, sometimes fever, myocarditis, and a strong inflammatory syndrome. Although not all children tested positive for SARS-CoV-2, all seem to have been in contact with the virus. No deaths have been reported so far. At the end of April, nearly 100 cases had been found in children in France, Great Britain, Italy, Spain, Switzerland and the United States.
On 1 May 2020, the Royal College of Paediatrics and Child Health released guidance describing a systemic inflammatory response sharing “common features with other pediatric inflammatory conditions including: Kawasaki disease, staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes (Royal College of Paediatrics and Child Health 2020).” On 4 May, New York City’s Department of Health issued a similar alert (NYC Health 2020). Two days later, 64 cases were reported from New York (New York Department of Health 2020).
Kawasaki disease (KD) is an acute-onset systemic vasculitis of medium-sized vessels that mostly affects infants and toddlers (Hedrich 2017).
The first English-language report of 50 patients goes back to Tomisaku Kawasaki in 1974 (Kawaski 1974, Burns 2000). The KD incidence is much higher in Northeast Asian countries including Japan, South Korea, China, and Taiwan, 10–30 times higher than that of KD in North America and Europe (see the world map in Kim GB 2019).
More than 90% of children were less than 5 years old in a study from Inner Mongolia (Zhu 2015). Untreated, KD leads to coronary artery aneurysms in around 25% of cases (don’t miss this paper: McCrindle 2017). The diagnosis of “classic KD” is based on the presence of ≥5 days of fever plus four out of five diagnostic criteria including erythema of the lips or mouth, trunk rash, swelling or erythema of the hands or feet, conjunctivitis, and lymph node swelling (see the detailed discussion in McCrindle 2017).
Prompt diagnosis is essential, immune globulin being the mainstay of initial treatment. Even in these COVID-19 times, physicians should keep an eye out for KD in all children with prolonged fever, especially in those younger than 1 year (Harasheh 2020).
The cause of KD remains unknown. Some lines of evidence point to a post-infectious trigger causing hyperreaction of the immune system (Dietz 2017) and an association between viral respiratory infections and KD (Jordan-Villegas 2010, Kim JH 2012, Turnier 2015). The primarily winter-spring KD seasonality and well-documented Japanese epidemics with wave-like spread also support an infectious trigger (Rowley 2018).
It is still unknown if there is a correlation between the cases described above and COVID-19. If there is a correlation, it is unclear whether COVID-19-associated inflammatory disorder and Kawasaki disease are identical (COVID-19-associated cases seem to have more severe abdominal pain, nausea and vomiting; those with severe shock are often older than the typical Kawasaki patients; and in Kawasaki cases, heart vessels seem to be more involved).
- A new Kawasaki-like syndrome may be emerging in children of all ages.
- The syndrome is rare.
- This syndrome may be related to SARS-CoV-2 but could as well be related to a different infectious pathogen with similar characteristics.
- So far, little is known about the new syndrome.
- To be remembered: serious COVID-19 complications are very rare among children. Throughout Europe, SARS-CoV-2 has caused very few victims among children. In Britain, only 9 children aged 0 to 19 have died after testing positive for coronavirus (0.05% of the 21,678 deaths recorded at the end of April).
See also selected press articles from France (Le Monde, Libération), UK (The Guardian), Spain (El País), Italy (Corriere della Sera) and Germany (FAZ).
Burns JC, Kushner HI, Bastian JF, et al. Kawasaki disease: A brief history. Pediatrics. 2000 Aug;106(2):E27. PubMed: https://pubmed.gov/10920183. Full-text: https://pediatrics.aappublications.org/content/106/2/e27
Dietz SM, van Stijn D, Burgner D, et al. Dissecting Kawasaki disease: a state-of-the-art review. Eur J Pediatr. 2017 Aug;176(8):995-1009. PubMed: https://pubmed.gov/28656474. Full-text: https://doi.org/10.1007/s00431-017-2937-5
Harahsheh AS, Dahdah N, Newburger JW, et al. Missed or Delayed Diagnosis of Kawasaki Disease During the 2019 Novel Coronavirus Disease (COVID-19) Pandemic. J Pediatr. 2020 Apr 23. PubMed: https://pubmed.gov/32370951. Full-text: https://doi.org/10.1016/j.jpeds.2020.04.052
Hedrich CM, Schnabel A, Hospach T. Kawasaki Disease. Front Pediatr. 2018 Jul 10;6:198. PubMed: https://pubmed.gov/30042935. Full-text: https://doi.org/10.3389/fped.2018.00198
Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr. 2020 Apr 7. PubMed: https://pubmed.gov/32265235. Full-text: https://doi.org/10.1542/hpeds.2020-0123 l (Important) – This is the first report about Kawasaki disease and concurrent SARS-CoV-2 infection. The authors describe the case of a a six-month-old baby girl with fever, rash and swelling characteristic of Kawasaki syndrom. The child had minimal respiratory symptoms. She was treated with a single dose of 2g/kg intravenous immunoglobulin (IVIG) and high dose acetylsalicylic acid (ASA 20mg/kg four times daily) according to treatment guidelines.
Jordan-Villegas A, Chang ML, Ramilo O, Mejias A. Concomitant respiratory viral infections in children with Kawasaki disease. Pediatr Infect Dis J. 2010 Aug;29(8):770-2. PubMed: https://pubmed.gov/20354462. Full-text: https://doi.org/10.1097/INF.0b013e3181dba70b
Kawaski T, Kosaki F, Okawa S, et al (1974) A new infantile acute febrile mucocutaneous lymph node syndrome (MCLS) prevailing in Japan. Pediatrics 54:271–276. Full-text: https://pediatrics.aappublications.org/content/pediatrics/54/3/271.full-text.pdf
Kim JH, Yu JJ, Lee J, et al. Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease. Korean J Pediatr. 2012 Dec;55(12):470-3. PubMed: https://pubmed.gov/23300502. Full-text: https://doi.org/10.3345/kjp.2012.55.12.470
Kim GB. Reality of Kawasaki disease epidemiology. Korean J Pediatr. 2019 Aug;62(8):292-296. PubMed: https://pubmed.gov/31319643. Full-text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702118/
McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017 Apr 25;135(17):e927-e999. PubMed: https://pubmed.gov/28356445. Full-text: https://doi.org/10.1161/CIR.0000000000000484
New York City’s Department of Health. 2020 Health Alert #13: Pediatric Multi-System Inflammatory Syndrome Potentially Associated with COVID-19. 4 May 2020 (accessed 6 May 2020). Document: https://www1.nyc.gov/assets/doh/downloads/pdf/han/alert/2020/covid-19-pediatric-multi-system-inflammatory-syndrome.pdf
New York Departement of Health. Healthadvisory: pediatric multi-system inflammatory syndrome potentially associated with coronavirus disease (covid-19) in children. 6 May 2020 (accessed 9 May 2020). Document: http://dmna.ny.gov/covid19/docs/all/DOH_COVID19_PediatricInflammatorySyndrome_050620.pdf
Paediatric Critical Care Society. PICS Statement: Increased number of reported cases of novel presentation of multi-system inflammatory disease. 27 April 2020 (accessed 7 May 2020). Document: https://picsociety.uk/wp-content/uploads/2020/04/PICS-statement-re-novel-KD-C19-presentation-v2-27042020.pdf
Rowley AH, Shulman ST. The Epidemiology and Pathogenesis of Kawasaki Disease. Front Pediatr. 2018 Dec 11;6:374. PubMed: https://pubmed.gov/30619784. Full-text: https://doi.org/10.3389/fped.2018.00374
Royal College of Paediatrics and Child Health. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. 1 May 2020 (accessed 4 May). Document: https://www.rcpch.ac.uk/resources/guidance-paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19
Turnier JL, Anderson MS, Heizer HR, Jone PN, Glode MP, Dominguez SR. Concurrent Respiratory Viruses and Kawasaki Disease. Pediatrics. 2015 Sep;136(3):e609-14. PubMed: https://pubmed.gov/26304824. Full-text: https://doi.org/10.1542/peds.2015-0950
Zhu H, Yu SF, Bai YX, Liang YY, Su XW, Pan JY. Kawasaki disease in children: Epidemiology, clinical symptoms and diagnostics of 231 cases in 10 years. Exp Ther Med. 2015 Jul;10(1):357-361. PubMed: https://pubmed.gov/26170962. Full-text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486877/
Chung SC, Providencia R, Sofat R, et al. Association between Angiotensin Blockade and Incidence of Influenza in the United Kingdom. NEJM May 8, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMc2005396
Like SARS-CoV-2, influenza A viruses have been shown to use the ACE2 receptor. Using the linked electronic health care records of 5.6 million persons in the United Kingdom, authors have investigated the incidence of influenza among adults who received a prescription for an ACE inhibitor from 1998 through 2016. Main results: the use of ACE inhibitors and ARBs was associated with either no effect on the incidence of influenza or a lower incidence.
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).
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.
Härter G, Spinner CD, Roider J, at al. COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients. Infection 2020, May 11. https://doi.org/10.1007/s15010-020-01438-z. Full-text https://link.springer.com/article/10.1007/s15010-020-01438-z. l (Important)
The first larger case series in HIV-infected patients. No excess morbidity and mortality was found among symptomatic COVID-19 cases. As the majority (22/33) was treated with tenofovir, including those developing severe or critical disease, data indicate no or only minimal clinical effect of tenofovir against SARS-CoV-2. Four patients also were on darunavir when they developed COVID-19 symptoms.
Xiong F, Tang H, Liu L, et al. Clinical Characteristics of and Medical Interventions for COVID-19 in Hemodialysis Patients in Wuhan, China. J Am Soc Nephrol. 2020 May 8. PubMed: https://pubmed.gov/32385130. Full-text: https://doi.org/10.1681/ASN.2020030354
First large (multicenter retrospective) study about epidemiologic and clinical characteristics of patients undergoing hemodialysis with COVID-19. There were 101 mild/moderate and 30 severe/critical cases. Of note, 28 (21%) were asymptomatic over the whole course of the disease and were diagnosed only by universal screening. Morbidity was around 2% and only 52% of patients experienced fever.
Menni, C., Valdes, A.M., Freidin, M.B. 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.
Alqahtani JS, Oyelade T, Aldhahir AM, et al. Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis. PLoS One. 2020 May 11;15(5):e0233147. PubMed: https://pubmed.gov/32392262. Full-text: https://doi.org/10.1371/journal.pone.0233147
Time to quit smoking. Meta-analysis of 15 studies, including a total of 2,473 confirmed cases. COPD patients were at a higher risk of more severe disease (calculated RR 1.88). Current smokers were 1.45 times more likely to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 39%.
Paul S, Rausch CR, Jain N, et al. Treating Leukemia in the Time of COVID-19. Acta Haematol. 2020 May 11:1-13. PubMed: https://pubmed.gov/32392559. Full-text: https://doi.org/10.1159/000508199
This paper offers some recommendations on the optimization of leukemia management during high-risk COVID-19 periods. Instead of reducing patient access to specialized cancer centers and modifying therapies to ones with unproven curative benefit, there is more rationale for less intensive yet effective therapies that may require fewer visits to the clinic or hospitalizations.
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://126.96.36.199/)
Latif F, Farr MA, Clerkin KJ, et al. Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019. JAMA Cardiol. 2020 May 13. PubMed: https://pubmed.gov/32402056. Full-text: https://doi.org/10.1001/jamacardio.2020.2159
Is there a higher mortality risk in heart transplanted patients? Probably yes. In this case series of 28 patients who had received a heart transplant in a large academic center (New York), 22 patients (79%) were hospitalized. At the end of the follow-up, 4 remained hospitalized and 7 (25%) had died.
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.
Mackey K, King VJ, Gurley S. Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults. A Living Systematic Review. Annals Internal Medicine 2020, May 15. Full-text: https://www.acpjournals.org/doi/10.7326/M20-1515
According to this review (data cut on May 4), evidence is of moderate certainty that ACEI and ARB use is not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result. Evidence is of high certainty (14 observational studies, involving 23,565 adults) that neither medication is associated with more severe COVID-19 illness. Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. For more information, see our special from May 4: https://covidreference.com/top-10-may-4.
Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. May 15, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMcp2009575 l (Important)
Comprehensive overview about current knowledge (and knowledge gaps) about treatment of patients who develop severe disease. Basics of respiratory care, ventilation management and supportive care. Areas of uncertainties are also discussed.
Lax SF, Skok K, Zechner P. Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series. Annals Int Med 2020, May 14. Full-text: https://www.acpjournals.org/doi/10.7326/M20-2566
The next autopsy study on 11 deceased patients with COVID-19 (10 selected randomly). Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.
Deshpande C. Thromboembolic Findings in COVID-19 Autopsies: Pulmonary Thrombosis or Embolism? Annals Int Med 2020, May 15. Full-text: https://doi.org/10.7326/M20-3255.
Well-balanced editorial, condensing current knowledge on the contributions of pulmonary thrombosis, embolism, or their combination to deaths of patients with COVID-19. Some studies have found pulmonary embolism with or without deep venous thrombosis, as well as presence of recent thrombi in prostatic venous plexus, in patients with no history of VTE, suggesting de novo coagulopathy in these patients with COVID-19. Others have highlighted changes consistent with thrombosis occurring within the pulmonary arterial circulation, in the absence of apparent embolism.
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.
Elharrar X, Trigui Y, Dols AM, et al. Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure. JAMA. May 15, 2020. Full-text: https://jamanetwork.com/journals/jama/fullarticle/2766292
This prospective, before-after study was conducted in Aix-en-Provence (France) among 24 awake, non-intubated, spontaneously breathing patients with COVID-19 and hypoxemic acute respiratory failure requiring oxygen supplementation. Efficacy of prone positioning was only moderate. Only 63% were able to tolerate PP for more than 3 hours. Oxygenation increased in only 25% and was not sustained in half of those after resupination. However, prone sessions were short, partly because of limited patient tolerance.
Telias I, Katira BH, Brochard L, et al. Is the Prone Position Helpful During Spontaneous Breathing in Patients With COVID-19? JAMA. Published online May 15, 2020. Full-text: https://doi.org/10.1001/jama.2020.8539
This editorial summarizes current knowledge on prone position. PP during spontaneous and assisted breathing may become a therapeutic intervention. Tolerance may be a limitation of the technique and the benefits of short sessions remain to be seen. Several larger trials are ongoing, addressing the question whether PP prevents intubation.
Bolay H, Gul A, Baykan B. COVID-19 is a Real Headache! Headache 2020 May 15. PubMed: https://pubmed.gov/32412101. Full-text: https://doi.org/10.1111/head.13856
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.
Tschopp J, L´Huillier AG, Mombelli M, et al. First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study. Am J Transplant 2020 May 15. PubMed: https://pubmed.gov/32412159. Full-text: https://doi.org/10.1111/ajt.16062
Data from Switzerland. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). Ninety‐five percent and 24% of patients required hospitalization and ICU admission, respectively. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died.
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.
Heman-Ackah SM, Su YS, Spadola M, MD. Neurologically Devastating Intraparenchymal Hemorrhage in COVID-19 Patients on Extracorporeal Membrane Oxygenation: A Case Series. Neurosurgery 2020. Full-text: https://doi.org/10.1093/neuros/nyaa198
Two patients required ECMO for refractory hypoxia secondary to COVID-19 and developed neurologically devastating intra-parenchymal hemorrhage despite lacking the classical risk factors. Authors recommend CT screening to identify brain injury that would otherwise go undetected due to the poor reliability of classic coagulation markers as accurate clinical predictors of hemorrhage in this cohort, as well as the inability to perform neurological assessments in the setting of paralysis, sedation, and proning.
Arjomandi Rad A, Vardanyan R, Tas NR. Ibuprofen and thromboembolism in SARS-COV2. J Thromb Haemost. 2020 May 16. PubMed: https://pubmed.gov/32415902. Full-text: https://doi.org/10.1111/jth.14901
Review of the literature on thromboembolic events (TE) associated with COVID-19. The causation between the effects of ibuprofen and TE remains speculative. The role of ibuprofen on a vascular level remains unclear as well as whether ibuprofen is able to interact with SARS-CoV-2 through some mechanism. However, the authors recommend careful consideration to avoiding a high dosage of ibuprofen in subjects at particular risk of thromboembolic events.
Michelozzi Paola, 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.
Brenner Ej, Ungaro RC, Gearry RB, et al. Corticosteroids, but Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry. Gastroenterology 2020 May 18. Full-text: https://doi.org/10.1053/j.gastro.2020.05.032
An important and large study, analysing 525 patients with IBD from 33 countries. Thirty-seven patients (7%) had severe COVID-19, and 16 patients died (3% case fatality rate). Risk factors for severe COVID-19 among IBD patients included increasing age, ≥2 comorbidities, systemic corticosteroids (aOR 6.9, 95% CI 2.3-20.5), and sulfasalazine or 5-aminosalicylate use (aOR 3.1, 95% CI 1.3-7.7). Maintaining remission with steroid-sparing treatments will be important in managing patients with IBD through this pandemic. However, a causal relationship cannot be definitively established. Notably, TNF antagonist treatment was not associated with severe COVID-19.
Solomon MD, McNulty EJ, Rana JS, et al. The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction. NEJM 2020, May 19. Full-text: HTTPS://DOI.ORG/10.1056/NEJMc2015630
In a large diverse community setting in California, the incidence of hospitalization for acute myocardial infarction declined after March 4 by up to 48% more than would be expected on the basis of typical seasonal variation alone. Similar findings have been noted in northern Italy.
George PM, Wells AU, Jenkins RG. Pulmonary Fibrosis and COVID-19: The Potential Role for Antifibrotic Therapy. Lancet Respir Med 2020 May 15; S2213-2600(20)30225-3. https://doi.org10.1016/S2213-2600(20)30225-3. Full-text: https://linkinghub.elsevier.com/retrieve/pii/S2213260020302253
This brilliant article gives an overview on the (potentially high) burden of fibrotic lung disease following SARS-CoV-2 infection. Post-viral fibrosis may lead to severe physiological impairment. Available antifibrotic therapies such as pirfenidone (a pyridone with a poorly understood mechanism of action) and the thyrosine kinase inhibitor nintedanib have broad antifibrotic activity regardless of etiology, and these drugs might have a role in attenuating profibrotic pathways in SARS-CoV-2 infection. Current knowledge and future strategies are discussed.
A Top 10 Speciel
An update on HIV infection in the current crisis
HIV infection is of particular interest in the current crisis. First, many patients take antiretroviral therapies that are thought to have some effects against SARS-CoV-2. Second, HIV serves as a model of cellular immune deficiency. Third and by the far most important point, the collateral damage caused by COVID-19 in the HIV population may be much higher than that of COVID-19 itself.
Inexplicably, information on the HIV population is still scarce. However, preliminary data suggest no elevated incidence of COVID-19. In 5,700 patients from New York, only 43 (0.8%) were found to be HIV-positive (Richardson 2020). Similar findings were reported from Chicago (Ridgeway 2020). In Barcelona where a local protocol included HIV serology for all hospitalized COVID-19 patients, 32/2102 (1.5%) were HIV-infected, among them only one single new HIV diagnosis (Miro 2020). Given the fact that HIV+ patients may be at higher risk for other infectious diseases such as STDs, these percentages were so low that some experts have already speculated on potential “protective” factors (i.e., antiviral therapies or immune activation). Moreover, a defective cellular immunity could paradoxically be protective for severe cytokine dysregulation, preventing the cytokine storm seen in severe COVID-19 cases.
Appropriately powered and designed studies that are needed to draw conclusions on the effect of COVID-19 are still lacking. However, our own retrospective analysis of 33 confirmed SARS-CoV-2 infections between March 11 and April 17 in 12 participating German HIV centers revealed no excess morbidity or mortality (Haerter 2020). The clinical case definition was mild in 25/33 cases (76%), severe in 2/33 cases (6%), and critical in 6/33 cases (18%). At the last follow up, 29/32 of patients with documented outcome (90%) had recovered. Three out of 32 patients had died. One patient was 82 years old, one had a CD4 T-cell count of 69/µl and one suffered from several comorbidities. A similar observation was made in Milan, Italy, where 45/47 patients with HIV and COVID-19 (only 28 with confirmed SARS-CoV-2 infection) recovered (Gervasoni 2020). In this study, as in our cohort, severe immune deficiency was rare. The last median CD4 count was 670/µl (range, 69 to 1715) and in 30/32 cases in our cohort, the latest HIV RNA was below 50 copies/mL (Härter 2020). It remains to be seen whether HIV patients with uncontrolled viremia and/or low CD4 cells are at higher risk for severe disease. It is also unclear whether immunity after infection remains impaired. However, there are case reports on delayed antibody response in HIV patients (Zhao 2020).
Another issue making HIV patients an interesting population is a potential effect of antiretroviral therapies against SARS-CoV-2. For lopinavir/r, some reports on beneficial effects in patients with SARS, MERS and COVID-19 exist, but the evidence remains poor. Several studies on lopinavir are still underway (see Treatment chapter). According to both the US DHHS and EACS statement, an ART regimen should not be changed to include a PI to prevent or treat COVID-19 (EACS 2020, US 2020). In our cohort, 4/33 (12%) patients were on darunavir when they developed COVID-19 symptoms. In the Milan Cohort, the rate of patients on a PI was 11% (Gervasoni 2020). Both studies indicate that PIs do not protect from SARS-CoV-2 infection. Beside the PI, we did not find any clear evidence for a protective effect of tenofovir. Tenofovir alafenamide has some chemical similarities to remdesivir and has been shown to bind to SARS-CoV-2 RNA polymerase (RdRp) with binding energies comparable to those of native nucleotides and to a similar extent as remdesivir. Consequently, tenofovir has recently been suggested as a potential treatment for COVID-19 (Elfiky 2020). In Spain, a large randomized Phase III placebo-controlled study (EPICOS, NCT04334928) compares the use of tenofovir disoproxil fumarate/emtricitabine, hydroxychloroquine or the combination of both versus placebo as prophylaxis for COVID-19 in healthcare workers. Our observation that the majority (22/33) of HIV+ patients with COVID-19 were treated with tenofovir, including those developing severe or critical disease, indicate no or only minimal clinical effect against SARS-CoV-2 (Härter 2020). In Milan, 42% were receiving a tenofovir-based regimen (Gervasoni 2020).
The most serious concern regarding HIV, however, is the collateral damage induced by COVID-19. In Western countries, only few HIV+ patients had problems in gaining access to their HIV medications or had trouble taking them due to COVID-19 or the plans to manage it (Sanchez 2020). In contrast, disruption to delivery of health care in sub-Saharan African settings could well lead to adverse consequences beyond those from COVID-19 itself. Lockdown, transport restrictions and fear of coronavirus infection have already led to a dramatic drop in HIV and TB patients collecting medication in several African countries (Adepoju 2020). Using five different existing mathematical models of HIV epidemiology and intervention programmes in sub-Saharan Africa, investigations have already estimated the impact of different disruptions to HIV prevention and treatment services. Predicted average relative excess in HIV-related deaths and new HIV infections (caused by unsuppressed HIV RNA during treatment interruptions) per year over 2020-2024 in countries in sub-Saharan Africa that would result from 3 months of disruption of specific HIV services, were 1.20-1.27 for death and 1.02-1.33 for new infections, respectively. A 6-month interruption of ART would result in over 500,000 excess HIV deaths in sub-Saharan Africa (range of estimates 471,000 – 673,000). Disrupted services could also reverse gains made in preventing mother-to-child transmission. According to WHO, there is a clear need for urgent efforts to ensure HIV service continuity and preventing treatment interruptions due to COVID-19 restrictions in sub-Saharan Africa.
Adepoju P. Tuberculosis and HIV responses threatened by COVID-19. Lancet HIV. 2020 May;7(5):e319-e320. PubMed: https://pubmed.gov/32277870. Full-text: https://doi.org/10.1016/S2352-3018(20)30109-0
EACS & BHIVA. Statement on risk of COVID-19 for people living with HIV (PLWH). https://www.eacsociety.org/home/covid-19-and-hiv.html
Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. 2020 Mar 25;253:117592. PubMed: https://pubmed.gov/32222463. Full-text: https://doi.org/10.1016/j.lfs.2020.117592
Gervasoni C, Meraviglia P, Riva A, et al. Clinical features and outcomes of HIV patients with coronavirus disease 2019. Clin Infect Dis. 2020 May 14:ciaa579. PubMed: https://pubmed.gov/32407467. Full-text: https://doi.org/10.1093/cid/ciaa579
Härter G, Spinner CD, Roider J, at al. COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients. Infection 2020, May 11. https://doi.org/10.1007/s15010-020-01438-z. Full-text: https://link.springer.com/article/10.1007/s15010-020-01438-z
Jewell B, Mudimu E, Stover J, et al. Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple models. Pre-print, https://doi.org/10.6084/m9.figshare.12279914.v1 + https://doi.org/10.6084/m9.figshare.12279932.v1
Miró JM, Ambrosioni J, Blanco JL. COVID-19 in patients with HIV – Authors’ reply. Lancet HIV. 2020 May 14:S2352-3018(20)30140-5. PubMed: https://pubmed.gov/32416770. Full-text: https://doi.org/10.1016/S2352-3018(20)30140-5
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:e206775. PubMed: https://pubmed.gov/32320003. Full-text: https://doi.org/10.1001/jama.2020.6775
Ridgway JP, Schmitt J, Friedman E, et al. HIV Care Continuum and COVID-19 Outcomes Among People Living with HIV During the COVID-19 Pandemic, Chicago, IL. AIDS Behav. 2020 May 7:1-3. PubMed: https://pubmed.gov/32382823. Full-text: https://doi.org/10.1007/s10461-020-02905-2
Sanchez TH, Zlotorzynska M, Rai M, Baral SD. Characterizing the Impact of COVID-19 on Men Who Have Sex with Men Across the United States in April, 2020. AIDS Behav. 2020 Apr 29:1-9. PubMed: https://pubmed.gov/32350773. Full-text: https://doi.org/10.1007/s10461-020-02894-2
U.S. Department of Health and Human Services. Interim Guidance for COVID-19 and Persons with HIV. https://aidsinfo.nih.gov/guidelines/html/8/covid-19-and-persons-with-hiv–interim-guidance-/554/interim-guidance-for-covid-19-and-persons-with-hiv
Zhao J, Liao X, Wang H, et al. Early virus clearance and delayed antibody response in a case of COVID-19 with a history of co-infection with HIV-1 and HCV. Clin Infect Dis. 2020 Apr 9:ciaa408. PubMed: https://pubmed.gov/32270178. Full-text: https://doi.org/10.1093/cid/ciaa408
Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020 May 21. PubMed: https://pubmed.gov/32437596. Full-text: https://doi.org/10.1056/NEJMoa2015432 l (Important)
It’s not influenza. The authors carefully examined lungs from 7 deceased COVID-19 patients with lungs from 7 patients who died from ARDS secondary to influenza A and 10 age-matched, uninfected control lungs. In COVID-19 or influenza, the histologic pattern was diffuse alveolar damage with perivascular T-cell infiltration. However, the COVID-19 lungs showed distinctive vascular features, consisting of severe endothelial injury associated with the presence of intracellular virus and disrupted cell membranes. Histologic analysis of pulmonary vessels showed widespread thrombosis with microangiopathy. Alveolar capillary microthrombi and the amount of vessel growth were 9 and almost 3 times as prevalent as in influenza, respectively.
Fan J, Zhang X, Liu J, et al. Connecting hydroxychloroquine in vitro antiviral activity to in vivo concentration for prediction of antiviral effect: a critical step in treating COVID-19 patients. Clin Infect Dis. 2020 May 21:ciaa623. PubMed: https://pubmed.gov/32435791. Full-text: https://doi.org/10.1093/cid/ciaa623
The price for the most cryptic abstract of the day goes to this FDA group. “Translation of in vitro antiviral activity to the in vivo setting is crucial to identify potentially effective dosing regimens of hydroxychloroquine. In vitro EC50/EC90 values for hydroxychloroquine should be compared to the in vivo free extracellular tissue concentration, which is similar to the free plasma hydroxychloroquine concentration.” Did they not dare to tell the truth? Their (important, yet cryptic) message was: HCQ doses tolerable for humans are too low to have any antiviral effect.
Parang K, El-Sayed NS, Kazeminy AJ, Tiwari RK. Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs Against Human Coronavirus 229E (HCoV-229E). Molecules. 2020 May 17;25(10):E2343. PubMed: https://pubmed.gov/32429580. Full-text: https://doi.org/10.3390/molecules25102343.
Most almost-misleading title of the day: Comparative, not comparable. A series of anti-HIV nucleosides were compared with remdesivir for antiviral activity against seasonal HCoV-229E in MRC-5 cells. Remdesivir was found to be potent, with an EC50 value of 0.07 μM. Only emtricitabine (FTC) showed modest activity, with an EC50 value of 82 μM. Other NRTIs did not show comparable activity. But it was comparative, yes.
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.
Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. N Engl J Med 2020, May 21; 382:2012-2022. Full-text: https://doi.org/10.1056/NEJMoa2004500
This report describes clinical characteristics, imaging findings, and outcomes among 24 critically ill COVID-19 patients who presented with acute hypoxemic respiratory failure in the Seattle metropolitan area. Mortality was high (at least 50%, three patients still intubated at last follow-up).
Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020 May 19:S0140-6736(20)31189-2. PubMed: https://pubmed.gov/32442528. Full-text: https://doi.org/10.1016/S0140-6736(20)31189-2l (Important)
More on critically ill patients. Among 1,150 adults who were admitted to two NYC hospitals with COVID-19 in March, 257 (22%) were critically ill. The median age of patients was 62 years (IQR 51-72), 67% were men and 82% patients had at least one chronic illness. As of the end of April, 101 (39%) patients had died and 94 (37%) remained hospitalised. 203 (79%) patients received invasive mechanical ventilation for a median of 18 days, 66% received vasopressors and 31% received renal replacement therapy. In the multivariable Cox model, older age, chronic cardiac disease (adjusted HR 1.76), chronic pulmonary disease (2.94) were independently associated with in-hospital mortality. This was also seen for higher concentrations of interleukin-6 and D-dimer, highlighting the role of systemic inflammation and endothelial-vascular damage in the development of organ dysfunction. Studies on immunomodulating and anticoagulant drugs are urgently needed.
Varga Z, Flammer AJ, Steiger P, et al. Electron microscopy of SARS-CoV-2: a challenging task – Authors’ reply. Lancet. 2020 May 19:S0140-6736(20)31185-5. PubMed: https://pubmed.gov/32442527. Full-text: https://doi.org/10.1016/S0140-6736(20)31185-5
Endothelial cell dysfunction may explain the vascular microcirculatory complications seen in different organs in patients with COVID-19. The authors discuss the framework of endotheliitis, providing explanation for the unique predilection of SARS-CoV-2 in those individuals with hypertension, diabetes, or established cardiovascular disease, groups known to have pre-existing endothelial dysfunction.
Schünemann HJ, Khabsa J, Solo K, et al. Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19. A Living Systematic Review of Multiple Streams of Evidence. Ann Int Med 2020, May 22. Full-text: https://www.acpjournals.org/doi/10.7326/M20-2306 l (Important)
The authors reviewed evidence regarding the benefits and harms of ventilation techniques. Indirect and low-certainty evidence suggests that use of non-invasive ventilation, similar to invasive mechanical ventilation, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers.
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.
Valente S, AnselmiF, Cameli M. Acute coronary syndromes during COVID-19. European Heart Journal, 2020, May 25. Full-text: https://doi.org/10.1093/eurheartj/ehaa457.
Brief guide for clinicians for managing different cases of STEMI/NSTEMI ACS with potential or known COVID-19 infection, based on recent worldwide evidence and standardization protocols.
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).
Lupo-Stanghellini MT, Messina C, Marktel S, et al. Following-up allogeneic transplantation recipients during the COVID-19 pandemic. Lancet Haematol. 2020 May 22:S2352-3026(20)30176-9. PubMed: https://pubmed.gov/32450053. Full-text: https://doi.org/10.1016/S2352-3026(20)30176-9
The authors describe their way of taking care of the most vulnerable patient groups using telemedicine. They contacted 236/465 adult patients who received an allogeneic transplantation. Physicians felt confident about the management of patients using teleconsultations, and patients—reassured that they were not left alone while in quarantine—provided positive feedback on this approach.
Gartshteyn Y, Askanase AD, Schmidt NM, et al. COVID-19 and systemic lupus erythematosus: a case series. Published: May 26, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30161-2
Of 18 SLE patients with COVID-19, most recovered. Previous intake of immunosuppressants before admission to hospital did not seem to influence the severity of infection.
Junejo M, Girometti N, McOwan A. HIV postexposure prophylaxis during COVID-19. May 25, 2020. Full-text: https://doi.org/10.1016/S2352-3018(20)30146-6
Weekly prescriptions of PEP at a large center in London dropped from a peak of 54 (from Feb 17–23, 2020) to four (from March 30–April 5, 2020) during lockdown. The most obvious explanation for this decline is that individuals are engaging in less condomless sex during lockdown. However, this might also reflect people’s reluctance to travel during this period, which would mean that individuals are not accessing the PEP they require.
Comment of the copy-editor: “And might also mean, that if they have less desire to travel, are hooking up less, and perhaps less sex is happening.”
Yahalom J, Dabaja BS, Ricardi U. ILROG emergency guidelines for radiation therapy of hematological malignancies during the COVID-19 pandemic. Blood 2020, 135 (21): 1829–1832. https://doi.org/10.1182/blood.2020006028
Realizing the need to reduce the exposure of patients and staff to potential infection with COVID-19, a task force makes recommendations for alternative radiation treatment schemes. The emphasis is on maintaining clinical efficacy and safety by increasing the dose per fraction while reducing the number of daily treatments.
Kuderer NM, Choueiri TK, Shah DP. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet May 28, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31187-9
Cohort study from the USA, Canada, and Spain, analysing 928 cancer patients with COVID-19. Median age was 66 years (IQR 57–76) and the most prevalent malignancies were breast (21%) and prostate (16%). In total 121 (13%) patients had died. Beside general risk factors (age, male sex etc), independent factors associated with increased mortality were an ECOG status of 2 or higher and “active” cancer.
Vizcarra P, Pérez-Elías M, Quereda C, et al. Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort. Lancet HIV. Published: May 28, 2020. Full-text: https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30164-8/fulltext l (Important)
Single center study from Madrid, comparing 51 HIV+ patients with COVID-19 (35 confirmed cases) with 1,288 HIV patients without COVID-19. Six patients were critically ill and two died. There was no evidence that any specific antiretroviral drug (such as tenofovir or PIs) affected COVID-19 susceptibility or severity.
Geerts H, van der Graaf PH. Salvaging CNS Clinical Trials halted due to COVID-19. CPT Pharmacometrics Syst Pharmacol. 2020 May 28. PubMed: https://pubmed.gov/32468710. Full-text: https://doi.org/10.1002/psp4.12535
COVID-19 has halted many ongoing CNS clinical trials, especially in Alzheimer’s disease. While some of these trials will need to restart, others can re-start at different points with substantial protocol amendments. Authors propose the concept of mechanistic modeling-based virtual twin patients as a possible solution to harmonize the readouts from these complex and fragmented clinical datasets in a biologically relevant way.
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)
Tian J, Yuan X, Xiao J, et al. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study. Lancet Oncology 2020, May 29. Full-text: https://10.1016/S1470-2045(20)30309-0
232 COVID-19 patients with cancer and were compared with 519 matched patients without cancer. Patients with cancer were more likely to have severe COVID-19 (64% versus 32%). Risk factors (of those well-known) for severe disease were advanced tumour stage (OR 2.60), elevated tumour necrosis factor α (1.22), elevated N-terminal pro-B-type natriuretic peptide (1.65).
COVIDSurg Collaborative. Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study. Lancet May 29, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31182-X l (Important)
This large cohort includes 1128 patients who had surgery between Jan 1 and March 31, 2020, among them 835 (74%) emergency surgery and 280 (25%) elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26%) patients. 30-day mortality was 24% and pulmonary complications occurred in 577 (51%). In adjusted analyses, 30-day mortality was associated with male sex (Odds Ratio 1.75), age 70 years or older (2.30), ASA grades 3–5 versus grades 1–2 (2.35), malignant versus benign (1.55), emergency versus elective surgery (1.67), and major versus minor surgery (1.52).
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.
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.
Tremblay D, van Gerwen M, Alsen M, et al. Impact of anticoagulation prior to COVID-19 infection: a propensity score-matched cohort study. Blood. 2020 May 27. PubMed: https://pubmed.gov/32462179. Full-text: https://doi.org/10.1182/blood.2020006941 l (Important)
Empiric therapeutic anti-coagulation (AC) is now being employed in clinical practice in many centers, and will be evaluated in randomized clinical trials. To adjust for bias due to non-random allocation of potential covariates among COVID-19 patients, the authors applied propensity score matching methods. Among > 3000 patients, propensity matching yielded 139 patients who received AC and 417 patients who did not receive treatment with balanced variables between the groups. Results suggest that AC alone is unlikely to be protective for COVID-19-related morbidity and mortality.
Shalev N, Scherer M, LaSota ED, et al. Clinical characteristics and outcomes in people living with HIV hospitalized for COVID-19. Clin Inf Dis 2020, May 30. Full-text: https://doi.org/10.1093/cid/ciaa635
31 people living with HIV (PLWH) were hospitalized for COVID-19. All patients were on antiretroviral therapy and virologically suppressed at the time of admission. One was mild (3%), 2 moderate (6.5%), 21 severe (60%) and 7 were critical (23%). At the time of analysis, 8 (25.8%) patients had died, 21 (67.7%) were alive and discharged and 2 (6.5%) were alive and hospitalized. Four deaths occurred in subjects over 65 years of age and 4 in patients between 50 and 65 years of age.
Gianfrancesco M, Hyrich KL, Al-Adely S, et al. Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2020 May 29. PubMed: https://pubmed.gov/32471903. Full-text: https://doi.org/10.1136/annrheumdis-2020-217871
Case series of 600 COVID-19 patients with rheumatic diseases from 40 countries. Nearly half of the cases were hospitalized (277 or 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalization but not the use of conventional disease-modifying anti-rheumatic drug (DMARD) alone or in combination with biologics, the Janus Kinase inhibitors. This is good news because only high glucocorticoid exposure (which has well-known side effects anyway) is associated with a higher odds of hospitalization but not either DMARDs or NSAIDs.
Kola, Lola. 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!).
Rubin EJ. Expression of Concern: Mehra MR et al. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med 2020, June 2. Full-text: https://doi.org/10.1056/NEJMoa2007621
Ooops. They don’t trust their own authors (Mehra 2020). “Recently, substantive concerns have been raised about the quality of the information in that database”, editor Eric Rubin writes, washing NEJM’s hands in innocence. “We have asked the authors to provide evidence that the data are reliable. In the interim and for the benefit of our readers, we are publishing this Expression of Concern about the reliability of their conclusions.” Ok. Let’s wait and see what happens. But bad news because even in a journal like NEJM, bad data quality is possible.
Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular disease, drug therapy, and mortality in Covid-19. N Engl J Med. Full-text: https://doi.org/10.1056/NEJMoa2007621
This was the original work of concern. Bad news that we cannot trust it. This was our comment: “The first study analyzed a total of 8,910 COVID-19 patients (from 169 hospitals located in 11 countries) for whom discharge status was availably by March 29 (Mehra 2020). A total of 515 (5.8%) died in the hospital. Factors independently associated with an increased risk of in-hospital death were an age greater than 65 years (odds ratio, 1.93), coronary artery disease (2.70), heart failure (2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (2.96; 95% CI, 2.00 to 4.40), and current smoking (1.79; 95% CI, 1.29 to 2.47). No increased risk was found for the use of ACE inhibitors (0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (1.23; 95% CI, 0.87 to 1.74). Of note, use of either ACE inhibitors or statins was associated with better survival. However, these associations should be considered with extreme caution as the study design cannot exclude the possibility of confounding.”
Kola, Lola. 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!).
Rubin EJ. Expression of Concern: Mehra MR et al. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med 2020, June 2. Full-text: https://doi.org/10.1056/NEJMoa2007621
Ooops. They don’t trust their own authors (Mehra 2020). “Recently, substantive concerns have been raised about the quality of the information in that database”, editor Eric Rubin writes, washing NEJM’s hands in innocence. “We have asked the authors to provide evidence that the data are reliable. In the interim and for the benefit of our readers, we are publishing this Expression of Concern about the reliability of their conclusions.” Ok. Let’s wait and see what happens. But bad news because even in a journal like NEJM, bad data quality is possible.
Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular disease, drug therapy, and mortality in Covid-19. N Engl J Med. Full-text: https://doi.org/10.1056/NEJMoa2007621
This was the original work of concern. Bad news that we cannot trust it. This was our comment: “The first study analyzed a total of 8,910 COVID-19 patients (from 169 hospitals located in 11 countries) for whom discharge status was availably by March 29 (Mehra 2020). A total of 515 (5.8%) died in the hospital. Factors independently associated with an increased risk of in-hospital death were an age greater than 65 years (odds ratio, 1.93), coronary artery disease (2.70), heart failure (2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (2.96; 95% CI, 2.00 to 4.40), and current smoking (1.79; 95% CI, 1.29 to 2.47). No increased risk was found for the use of ACE inhibitors (0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (1.23; 95% CI, 0.87 to 1.74). Of note, use of either ACE inhibitors or statins was associated with better survival. However, these associations should be considered with extreme caution as the study design cannot exclude the possibility of confounding.”
Boulware DR, Pullen MF, Bangdiwala AS, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020 Jun 3:NEJMoa2016638. PubMed: https://pubmed.gov/32492293. Full-text: https://doi.org/10.1056/NEJMoa2016638 ll (Outstanding)
In total, 821 asymptomatic participants were randomized to receive hydroxychloroquine or placebo within 4 days after exposure (88% with a high-risk exposure). Incidence of confirmed SARS-CoV-2 was 11.8% with CQ and 14.3% with placebo. Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.
This is bad news because after high-risk or moderate-risk exposure to Covid-19, HCQ did not prevent infection when used as postexposure prophylaxis within 4 days after exposure.
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.
Al-Samkari H, Karp Leaf RS, Dzik WH, et al. COVID and Coagulation: Bleeding and Thrombotic Manifestations of SARS-CoV2 Infection. Blood. 2020 Jun 3:blood.2020006520. PubMed: https://pubmed.gov/32492712. Full-text: https://doi.org/10.1182/blood.2020006520
Retrospective study, describing the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill), receiving standard-dose prophylactic anticoagulation. The overall and major bleeding rates were 4.8% and 2.3%. RCTs are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.
Belli LC, Duvoux C, Karam V, et al. COVID-19 in liver transplant recipients: preliminary data from the ELITA/ELTR registry. Lancet Gastroenterology & Hepatology, June 4, 2020. Full-text: https://doi.org/10.1016/S2468-1253(20)30183-7
First large analysis on liver transplant recipients. At a median follow-up of 18 days, 16/100 died from COVID-19. Of note, mortality was observed only in patients aged 60 years or older (16/73) and was more common in male recipients than in female recipients. Although not statistically significant, more patients who were transplanted at least 2 years earlier died than did those who received their transplant within the past 2 years (15/82, 18% vs 1/21, 5%).
Ferreyro BL, Angriman F, Munshi L, et al. Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure. JAMA June 4, 2020. Full-text: https://doi.org/10.1001/jama.2020.9524
For this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, the authors included 25 studies with 3,804 patients. Compared with standard oxygen therapy, helmet NIV (3 trials with 330 patients), face mask NIV (14 trials with 1725 patients) and HFNC (5 trials with 1479 patients) were associated with a lower risk of endotracheal intubation. Both forms of NIV, helmet and face mask, were also associated with a lower risk of death.
Patel BK, Kress JP, Hall JB. Alternatives to Invasive Ventilation in the COVID-19 Pandemic. JAMA June 4, 2020. Full-text: https://doi.org/10.1001/jama.2020.9611
This article reviews the meta-analysis and describes how COVID-19 has accelerated the need to add clarity to the ongoing debate of whether to intubate early and, if not, which type of non-invasive support (NIV, HFNC, or standard oxygen therapy) is the most efficacious. Future clinical trials comparing these strategies should not focus on declaring a “winner” per se but rather on identifying the patient phenotypes that stand to benefit from each non-invasive oxygenation support method. According to the authors, a heterogeneous syndrome like AHRF requires multiple options.
Von Weyhern C, Kaufmann I, Neff F, Kremer M. Early evidence of pronounced brain involvement in fatal COVID-19 outcomes. The Lancet, June 4, 2020. Full-text: https://doi.org/10.1016/S0140-6736(20)31282-4
Autopsy findings of six patients (four men and two women, aged 58–82 years) who died from COVID-19 in April 2020. A pronounced CNS involvement with pan-encephalitis, meningitis, and brainstem neuronal cell damage were key events in all cases. In patients younger than 65 years, CNS hemorrhage was a fatal complication of COVID-19.
Carsana L, Sonzogni A, Nasr A, et al. Pulmonary post-mortem findings in a series of COVID-19 cases. Lancet 2020, June 08. Full-text: https://doi.org/10.1016/S1473-3099(20)30434-5
Lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy were analyzed. The predominant pattern was diffuse alveolar damage, as described in patients infected with SARS and MERS. Hyaline membrane formation and pneumocyte atypical hyperplasia were frequent. However, the presence of platelet–fibrin thrombi in small arterial vessels was consistent with coagulopathy, which appears to be common in patients with COVID-19.
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).
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).
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.
Pinto BGG, Oliveira AER, Singh Y, et al. ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19. J Infect Dis. 2020 Jun 11:jiaa332. PubMed: https://pubmed.gov/32526012. Full-text: https://doi.org/10.1093/infdis/jiaa332
The authors analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. Findings suggest that the higher expression of ACE2 in the lungs is associated with higher chances of developing a severe form of COVID-19, by facilitating SARS-CoV-2 entry into lung cells during the infection.
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).
Endeman H, van der Zee P, van Genderen ME, van den Akker JPC, Gommers D. Progressive respiratory failure in COVID-19: a hypothesis. Lancet Infect Dis. 2020 Apr 29:S1473-3099(20)30366-2. PubMed: https://pubmed.gov/32530428. Full-text: https://doi.org/10.1016/S1473-3099(20)30366-2
Of 90 patients with severe COVID-19, 17 deteriorated within 2 weeks and no longer responded to prone positioning. All (!) of these patients had major pulmonary embolism established by lung CT or cardiac ultrasound. A plasma D-dimer concentration greater than 4 μg/mL, combined with increasing inflammatory markers such as interleukin-6 (the authors recommend to measure it regularly), and loss of response to prone positioning might be useful parameters to identify patients at risk of pulmonary embolism.
Gabarre P, Dumas G, Dupont T, Darmon M, Azoulay E, Zafrani L. Acute kidney injury in critically ill patients with COVID-19. Intensive Care Med. 2020 Jun 12. PubMed: https://pubmed.gov/32533197. Full-text: https://doi.org/10.1007/s00134-020-06153-9
One of the best reviews on this topic to date. AKI is prevalent in critically ill COVID-19 patients. Several mechanisms are possibly involved, including direct invasion of SARS-CoV-2 into the renal parenchyma, an imbalanced RAAS and microthrombosis, but also kidney injury secondary to hemodynamic instability, inflammatory cytokines and the consequences of therapeutics that are used in ICU (nephrotoxic drugs, mechanical ventilation).
Doglietto F, Vezzoli M, Gheza F, et al. Factors Associated With Surgical Mortality and Complications Among Patients With and Without Coronavirus Disease 2019 (COVID-19) in Italy. JAMA Surg. 2020 Jun 12. PubMed: https://pubmed.gov/32530453. Full-text: https://doi.org/10.1001/jamasurg.2020.2713
There is no good time for surgery: In this cohort study of 41 surgical patients with COVID-19 and 82 tightly matched control patients, significant differences were documented regarding rates of early mortality and complications (odds ratios 9.5 and 5.0, respectively), mainly pneumonia and thrombotic complications, were significantly associated with COVID-19, and different models identified COVID-19 as the first variable associated with surgical complications. These data suggest that, whenever possible, surgery should be postponed in patients with COVID-19.
Furfaro F, Vuitton L, Fiorino G, et al. SFED recommendations for IBD endoscopy during COVID-19 pandemic: Italian and French experience. Nat Rev Gastroenterol Hepatol. 2020 Jun 11:1-10. PubMed: https://pubmed.gov/32528139. Full-text: https://doi.org/10.1038/s41575-020-0319-3
This perspective aims to provide a guide based on the Italian and French experience to better face the difficulties encountered by endoscopists during this pandemic. Some helpful recommendations regarding the use of personal protective equipment (both for patients and HCW) are proposed and different scenarios in endoscopic IBD management are evaluated to suggest when endoscopy could be rescheduled and replaced by alternative biomarkers.
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%.
Piccolo R, Bruzzese D, Mauro C, et al. Population Trends in Rates of Percutaneous Coronary Revascularization for Acute Coronary Syndromes Associated With the COVID-19 Outbreak. Circulation. 2020 Jun 16; 141(24): 2035–2037. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047457
This study investigated the association between the outbreak of COVID-19 and PCI rates for ACS (Acute Coronary Syndromes) in the Campania region, which, with 5.8 million residents, represents ≈10% of the Italian population. The outbreak was associated with a decline in the number of PCIs for ACS by 32%. In the last 2 weeks of the observational period, PCIs for ACS were reduced by 50%. In comparison with PCI volumes for the same time in 2019, the decline in PCI rates was of a similar magnitude (between 36% and 38%).
Garassino MC, Whisenant JG, Huang LC, et al. COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study. Lancet Oncol. 2020 Jun 12:S1470-2045(20)30314-4. PubMed: https://pubmed.gov/32539942. Full-text: https://doi.org/10.1016/S1470-2045(20)30314-4
Of 200 patients with COVID-19 and thoracic cancers (76% NSCLC) from eight countries were identified and included in the TERAVOLT registry, 152 (76%) were hospitalised and 66 (33%) died. Of note, in a multivariable analysis, only smoking history (OR 3.18, 95% CI 1.11-9.06) was associated with increased risk of death.
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.
Thompson AE, Ranard BL, Wei Y. Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure. JAMA Intern Med June 17, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.3030
The next study on proning. In this small single-center cohort study, use of the prone position for 25 awake, spontaneously breathing patients with COVID-19 was associated with improved oxygenation. In addition, patients with an Spo2 of 95% or greater after 1 hour of the prone position was associated with a lower rate of intubation. Unfortunately, there was no control group and the sample size was very small. Ongoing clinical trials of prone positioning in non–mechanically ventilated patients (NCT04383613, NCT04359797) will hopefully help clarify the role of this simple, low-cost approach for patients with acute hypoxemic respiratory failure.
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.
Arlet JB, de Luna G, Khimoud D, et al. Prognosis of patients with sickle cell disease and COVID-19: a French experience. Lancet Hematology 2020, June 18. Full-text: https://doi.org/10.1016/S2352-3026(20)30204-0
Results of this French cohort of 83 patients suggest that COVID-19, even if potentially severe, does not seem to carry an increased risk of morbidity or mortality in patients with sickle cell disease, as most patients worldwide have the SS/Sβ0 genotype and are younger than 45 years.
Zeidan AM, Poddu P, Patniak MM, et al. Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts. Lancet Hematology 2020, June 18. Full-text: https://doi.org/10.1016/S2352-3026(20)30205-2
This article summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. It also offers a consensus on clinical practice guidance for optimal care in both the university and community health-care settings.
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.
Fosbøl EL, Butt JH, Østergaard L, et al. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. JAMA June 19, 2020. Full-text: https://doi.org/10.1001/jama.2020.11301
ACE inhibitors are not harmful, even in Denmark (one of the countries with the best epidemiological data). In a retrospective cohort study of 4,480 (!) patients diagnosed as having COVID-19, prior ACEI/ARB use, compared with no use, was not significantly associated with mortality (adjusted hazard ratio, 0.83). In a nested case-control study of a cohort of 494,170 patients with hypertension, use of ACEI/ARB, compared with use of other antihypertensive medications, was not significantly associated with COVID-19 diagnosis (adjusted hazard ratio, 1.05).
Lai PH, Lancet EA, Weiden MD. Characteristics Associated With Out-of-Hospital Cardiac Arrests and Resuscitations During the Novel Coronavirus Disease 2019 Pandemic in New York City. JAMA Cardiol. Published online June 19, 2020. Full-text: https://doi.org/10.1001/jamacardio.2020.2488
In this population-based cross-sectional study of 5,325 patients with out-of-hospital cardiac arrests in New York City, the number undergoing resuscitation was 3-fold higher during the COVID-19 period compared with the similar period in 2019. The authors report 2,653 excess out-of-hospital cardiac arrests (90% of these excess cases resulted in out-of-hospital deaths).
Koopmann A, Ekaterini G, Falk K, et al. Did the General Population in Germany Drink More Alcohol during the COVID-19 Pandemic Lockdown? Alcohol and Alcoholism, June 19 20020. Full-text: https://doi.org/10.1093/alcalc/agaa058
Question of the day. Answer: Some did so, yes. Out of the 2,102 participants of this survey, 34.7% reported drinking “more or much more” alcohol since the begin of the lockdown. Binary logistic regression analyses showed that especially low educated subjects and subjects with higher levels of perceived stress due to the lockdown were at risk of consuming more alcohol during the lockdown.
Cappo A, Bellani G, Wintertin D, et al. Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study. Lancet Resp Med June 19, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30268-X
This prospective cohort study enrolled 56 patients with COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure. Prone positioning was feasible in most patients and effective in rapidly ameliorating blood oxygenation. The effect was maintained after resupination in half of the patients.
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.
Colling ME, Kanthi Y. COVID-19-associated coagulopathy: An exploration of mechanisms. Vasc Med. 2020 Jun 19:1358863X20932640. PubMed: https://pubmed.gov/32558620. Full-text: https://doi.org/10.1177/1358863X20932640 l (Important)
Nice review of the laboratory and clinical findings of patients with COVID-19-associated coagulopathy. The authors hypothesize that an imbalance between coagulation and inflammation may result in a hypercoagulable state. Although thrombosis initiated by the innate immune system is hypothesized to limit SARS-CoV-2 dissemination, aberrant activation of this system can cause endothelial injury resulting in loss of thromboprotective mechanisms, excess thrombin generation, and dysregulation of fibrinolysis and thrombosis.
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.
El-Sharkawi D, Iyengar S. Haematological Cancers and the risk of severe COVID-19: Exploration and critical evaluation of the evidence to date. Br J Haematol. 2020 Jun 19. PubMed: https://pubmed.gov/32559308. Full-text: https://doi.org/10.1111/bjh.16956
The authors review the evidence to date to see whether a history of hematological malignancy is associated with increased risk of COVID‐19. Results: Multivariable analysis does indicate that patients with hematological malignancy, especially those diagnosed recently, are at increased risk of death with COVID‐19 compared to the general population. The evidence that this risk is higher than for those with solid malignancies is conflicting. There is suggestive evidence from smaller cohort studies that those with myeloid malignancy may be at increased risk within the blood cancer population, but this needs to be confirmed through larger studies.
Ibáñez-Samaniego L, Bighelli F, Usón C, et al. Elevation of liver fibrosis index FIB-4 is associated with poor clinical outcomes in patients with COVID-19. J Infect Dis. 2020 Jun 21:jiaa355. PubMed: https://pubmed.gov/32563190. Full-text: https://doi.org/10.1093/infdis/jiaa355
In middle-aged patients with COVID-19, the FIB-4 index may have a relevant prognostic role. In a multivariate analysis, among other risk factors, a FIB-4 > 2.67 increased the risk of ICU admission significantly (OR 3.41; 95% CI 1.30-8.92).
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).
Lange SJ, Ritchey MD, Goodman AB, et al. Potential Indirect Effects of the COVID-19 Pandemic on Use of Emergency Departments for Acute Life-Threatening Conditions — United States, January–May 2020. MMWR Morb Mortal Wkly Rep. ePub: 22 June 2020. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6925e2.htm
National syndromic surveillance data has found that emergency department (ED) visits declined 42% during the early months of the pandemic. This report describes trends in ED visits for three acute life-threatening health conditions, immediately before and after declaration of the COVID-19 pandemic as a national emergency: in the 10 weeks following the declaration, ED visits declined 23% for heart attack, 20% for stroke, and 10% for hyperglycemic crisis. The substantial reduction might be explained by many pandemic-related factors including fear of exposure to COVID-19, unintended consequences of public health recommendations to minimize non-urgent health care, stay-at-home orders, or other reasons.
Pfeifer M, Ewig S, Voshaar T, et al. Position Paper for the State-of-the-Art Application of Respiratory Support in Patients with COVID-19. Respiration. 2020 Jun 19:1-21. PubMed: https://pubmed.gov/32564028. Full-text: https://doi.org/10.1159/000509104 ll (Outstanding)
Important statements including observations about the pathophysiology of acute respiratory failure (ARF). Pulmonary damage in advanced COVID-19 often differs from acute respiratory distress syndrome (ARDS). Two types (type L and type H) are differentiated, corresponding to early- and late-stage lung damage. This differentiation should be taken into consideration in respiratory support. Based on current knowledge, inhalation therapy, nasal high-flow therapy (NHF), continuous positive airway pressure (CPAP), or non-invasive ventilation (NIV) can be performed without an increased risk of infection to staff if PPE is provided. In ARF, NIV should be carried out in an intensive care unit or a comparable setting by experienced staff. If the ARF progresses under CPAP/NIV, intubation should be implemented without delay in patients who do not have a “do not intubate”.
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).
Kent DG, Knapp DJ, Kannan N. Survey Says: “COVID-19 Lockdown Hits Young Faculty and Clinical Trials“. Stem Cells Rep June 22, 2020. Full-text: https://doi.org/10.1016/j.stemcr.2020.06.010
The survey was conducted from 6 to 15 April, 2020 and filled out by 762 researchers from 52 countries. It captured opinions from across all career stages on how COVID-19 has severely impacted laboratory research (i.e., 65% of laboratories were mostly or completely shut). From the crippling of ongoing and planned clinical trials across the full breadth of stem cell research to the devastating loss of productivity for those researchers near career transitions, the survey revealed some of the bleak truths on the impact of COVID-19 in the stem cell community.
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.
Zhang XJ, Quin JJ, Cheng X, et al. In-hospital Use of Statins is Associated with a Reduced Risk of Mortality among Individuals with COVID-19. Cell Metabolism June 24, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.06.015
Retrospective study on 13,981 patients in Hubei Province, China, among which 1,219 received statins. Based on a Cox model with time-varying exposure and after propensity score-matching, 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively. Randomized controlled trials involving statin treatment for COVID-19 are needed.
Robilotti EV, Babady NE, Mead PA, et al. Determinants of COVID-19 disease severity in patients with cancer. Nat Med June 24, 2020. Full-text: https://doi.org/10.1038/s41591-020-0979-0
Among 423 cases of symptomatic COVID-19 who were diagnosed at Memorial Sloan Kettering Cancer Center, 40% were hospitalized for COVID-19 and 12% died within 30 days. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not.
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.
Meca-Lallana V, Aguirre C, Beatrizdel Río, Cardeñoso L, Alarcon T, Vivancos J. COVID-19 in 7 multiple sclerosis patients in treatment with ANTI-CD20 therapies. Mult Scler Relat Disord. 2020 Jun 15;44:102306. PubMed: https://pubmed.gov/32585617. Full-text: https://doi.org/10.1016/j.msard.2020.102306
A small case series on patients with MS and COVID-19, treated with the anti-CD20 monoclonal antibodies (mAbs) ocrelizumab and rituximab. Although the severity of the clinical picture varied, patients’ development was good, indicating that B cells and immunoglobulin may not be absolutely necessary for viral elimination. Not all patients developed antibodies against SARS-CoV-2.
Sivaloganathan H, Ladikou EE, Chevassut T. COVID-19 mortality in patients on anticoagulants and antiplatelet agents. Br J Haematol. 2020 Jun 25. PubMed: https://pubmed.gov/32584423. Full-text: https://doi.org/10.1111/bjh.16968
Anticoagulants, or other antithrombotic agents such as antiplatelet drugs, might counteract the coagulopathic effects of COVID-19 resulting in improved outcomes. This small, matched-control study shows that this is probably not the case. Patients on aspirin (n=18), on clopidogrel (n=8), apixaban (n=12), warfarin (n=7) and some other drugs did not have a significantly different mortality risk to patients not taking these drugs. According to the authors, this could suggest these agents negate any potential increased mortality risk attributable to whichever disease the drugs had been prescribed, but further data on comorbidities is required to confirm this assertion.
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).
Louapre C, Collongues N, Stankoff B, et al. Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis. JAMA Neurol 2020, June 26. Full-text: https://doi.org/10.1001/jamaneurol.2020.2581
This registry-based cohort study from France has included 347 patients with MS with a confirmed or highly suspected diagnosis of COVID-19. In total, 73 patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died. Age, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), and obesity were independent risk factors for severe COVID-19; there was no association found between exposure to disease-modifying therapies and severity.
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.
Tison GH, Avram R, Kuhar P, et al. Worldwide Effect of COVID-19 on Physical Activity: A Descriptive Study. Ann Int Med 2020, June 29. Full-text: https://doi.org/10.7326/M20-2665
Big data: Using data from a popular health and wellness smartphone app (Argus), a rapid worldwide step count decrease was seen during the COVID-19 pandemic, with regional variability. Samples from different countries varied widely in the number of days after pandemic declaration that a 15% step count decrease was seen: Italy (5 days), Spain (9 days), France (12 days), India (14 days), the United States (15 days), the United Kingdom (17 days), Australia (19 days), and Japan (24 days).
McGonagle D, O’Donnell JS, Sharif K. Pulmonary intravascular coagulopathy in COVID-19 pneumonia – Authors’ reply. Lancet June 29, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30174-0
Interesting discussion about the diffuse, alveolar-centred inflammation that triggers immunothrombosis in the lung microvasculature of patients with COVID-19 pneumonia. It seems highly probable that multiple mechanisms contribute to the pulmonary intravascular coagulopathy.
Mangalmurti N, Hunter CA. Cytokine Storms: Understanding COVID-19. Immunity June 28, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.06.017 l (Important)
Facing the storm: In their nice overview, the authors explain the protective function of cytokines in “ideal” responses; the multi-factorial origins that can drive these responses to become pathological; and how this ultimately leads to vascular damage, immunopathology, and worsening clinical outcomes. Of note, not all cytokine storms are the same, and there are many variables—the nature of the insult, host immune status, tissue affected, crosstalk with immune thrombosis, and complement activation—that influence the magnitude and kinetics of these responses and thus the clinical manifestations.
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.
Goshua G, Pine AB, Meizlish ML, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet June 30, 2020. Full-text: https://doi.org/10.1016/S2352-3026(20)30216-7
In 68 COVID-19 patients, the authors assessed several markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen and soluble P-selectin. Some were of prognostic value, indicating that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.
Del Amo J, Polo R, Moreno S, et al. Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy – A Cohort Study. Annals Int Med 2020, June 26. Full-text: https://doi.org/10.7326/M20-3689
Is there an effect of TDF? Of 77,590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. However, residual confounding by comorbid conditions cannot be completely excluded.
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.
Sinha P, Matthay MA, Calfee CS. Is a “Cytokine Storm” Relevant to COVID-19? JAMA Intern Med June 30, 2020. Full-text: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2767939 l (Important)
“Cytokine storm” has no definition. Broadly speaking, it denotes a hyperactive immune response characterized by the release of interferons, interleukins, tumor necrosis factors, chemokines, and several other mediators. In this editorial, a critical evaluation of the term cytokine storm and its relevance is given. The authors point out that although the term “cytokine storm” conjures up dramatic imagery and has captured the attention of the mainstream and scientific media, the current data do not support its use. Until new data establish otherwise, the linkage of cytokine storm to COVID-19 may be nothing more than a tempest in a teapot.
Armeni E, Aziz U, Qamar S, et al. Protracted ketonaemia in hyperglycaemic emergencies in COVID-19: a retrospective case series. Lancet Diabetol Endocrinol July 01, 2020. Full-text: https://doi.org/10.1016/S2213-8587(20)30221-7
COVID-19 is associated with hyperglycemic emergencies in COVID-19. In this case series of 35 patients from three hospitals in north London, UK, March 1–30, 2020, an over-representation of type 2 diabetes in patients presenting with diabetic ketoacidosis and long-lasting ketosis was observed. Findings suggest acute insulinopenia in patients with COVID-19 and with type 2 diabetes, which persisted up until the time of discharge in 30% of patients previously not insulin-treated. Moreover, the study sample, with almost half of patients of African background, had protracted ketonemia and ketoacidosis.
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%.
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.
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.
Stanworth SJ, New HV, Apelseth TO, et al. Effects of the COVID-19 pandemic on supply and use of blood for transfusion. Lancet Hematology, July 03, 2020. Full-text: https://doi.org/10.1016/S2352-3026(20)30186-1
The pandemic has major implications for blood transfusion. There are uncertain patterns of demand, and transfusion institutions need to plan for reductions in donations and loss of crucial staff because of sickness and public health restrictions. This article provides a synthesis of the published literature and guidance during times of potential or actual shortage. However, a reduction in donor numbers has largely been matched by reductions in demand for transfusion.
Zhong J, Shen G, Yang H, et al. COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study. Lancet Rheumatology July 03, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30227-7
Patients with autoimmune rheumatic disease might be more susceptible. Within 42 families with at least one member suffering from a rheumatic disease, COVID-19 was diagnosed in 27 (63%) of 43 patients with a rheumatic disease and in 28 (34%) of 83 of their family members with no rheumatic disease (adjusted odds ratio 2.68, 95% CI 1.14–6.27). Patients with rheumatic disease who were taking hydroxychloroquine had a lower risk of COVID-19 infection than patients taking other disease-modifying anti-rheumatic drugs (OR 0.09, 0.01–0.94).
Tadic M, Cuspidi C, Grassi G, Mancia G. COVID-19 and arterial hypertension: Hypothesis or evidence? J Clin Hypertens (Greenwich). 2020 Jul 6. PubMed: https://pubmed.gov/32627330. Full-text: https://doi.org/10.1111/jch.13925
Hypertension has been proven to be more prevalent in patients with an adverse outcome. So far, there is no study that demonstrates the independent predictive value of hypertension on mortality in COVID-19 patients. This review summarizes the current knowledge about the relationship between hypertension and COVID‐19 and the role of hypertension on outcome in these patients.
Kollias A, Kyriakoulis KG, Stergiou GS, Syrigos K. Heterogeneity in reporting venous thromboembolic phenotypes in COVID-19: Methodological issues and clinical implications. Br J Haematol. 2020 Jul 4. PubMed: https://pubmed.gov/32621757. Full-text: https://doi.org/10.1111/bjh.16993
Some thoughts about the heterogeneity in the reported VTE risk as well as in the thromboembolic phenotypes of COVID-19 patients (isolated DVT, isolated pulmonary embolism/thrombosis, concurrent DVT and pulmonary embolism/thrombosis). It might be suggested that variation in VTE accounts for this heterogeneity: characteristics of the patients include well-established risk factors for VTE, hospitalization conditions and interventions as well as SARS-CoV-2 specific factors.
Nightingale R, Nwosu N, Kutubudin F, et al. Is continuous positive airway pressure (CPAP) a new standard of care for type 1 respiratory failure in COVID-19 patients? A retrospective observational study of a dedicated COVID-19 CPAP service. BMJ Open Respir Res. 2020 Jul;7(1):e000639. PubMed: https://pubmed.gov/32624495. Full-text: https://doi.org/10.1136/bmjresp-2020-000639
Small retrospective study of 24 patients. According to the authors, with careful patient selection and close monitoring, CPAP can be a successful treatment strategy in critically ill patients with type 1 respiratory failure in COVID-19, and that it can be safely deployed outside the critical care environment.
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.
Fan E, Beitler JR, Brochard L, et al. COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted? Lancet Respir Med July 06, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30304-0 l (Important)
In their Viewpoint, the authors address ventilation strategies in the context of recent discussions on phenotypic heterogeneity in patients with COVID-19-associated ARDS. Although early reports suggested distinctive features that set it apart from historical ARDS, emerging evidence indicates that the respiratory system mechanics are broadly similar. In the absence of evidence to support a shift away from the current paradigm of ventilatory management, we strongly recommend adherence to evidence-based management, informed by bedside physiology, as resources permit.
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.
Ackermann M, Verlden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. NEJM July 9, 2020; 383:120-128. Full-text: https://doi.org/10.1056/NEJMoa2015432 l (Important)
This study examined the morphologic and molecular features of seven lungs obtained during autopsy from COVID-19 patients and found three distinctive angiocentric features: 1. Severe endothelial injury associated with intracellular virus and disrupted endothelial cell membranes. 2. Widespread vascular thrombosis with microangiopathy and occlusion of alveolar capillaries (9 times as prevalent as in patients with influenza). 3. significant new vessel growth through a mechanism of intussusceptive angiogenesis (2.7 x higher).
Panepinto JA, Brandow A, Mucalo L, et al. Coronavirus disease among persons with sickle cell disease, United States, March 20–May 21, 2020. Emerg Infect Dis. 2020 Oct. Full-text: https://doi.org/10.3201/eid2610.202792
Sickle cell disease (SCD) disproportionately affects Black or African-American persons in the United States and can cause multisystem organ damage and reduced lifespan. Among 178 persons with SCD in the US who were reported to an SCD–coronavirus disease case registry, 122 (69%) were hospitalized and 13 (7%) died. According to the authors, this is alarming, given that the mean patient age was < 40 years. However, there may be bias toward more severe cases in this registry.
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.
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%).
Liao D, Zhou F, Luo L, et al. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Hematology July 10, 2020. Full-text: https://doi.org/10.1016/S2352-3026(20)30217-9
This retrospective cohort study focussed on hematological and coagulation parameters in patients with moderate, severe, and critical COVID-19, along with specific analyses of coagulopathy in non-survivors. Among 380 patients, thrombocytopenia was more frequent in patients with critical disease (49%) than in those with severe (14%) or moderate (6%). In multivariate analyses, death was associated with increased neutrophil to lymphocyte ratio (odds ratio 5.39), thrombocytopenia (OR 8.33), prolonged prothrombin time (OR 4.94), and increased D-dimer (OR 4.41). The onset of sepsis-induced coagulopathy was typically before overt disseminated intravascular coagulation.
Kander T. Coagulation disorder in COVID-19. Lancet Hematology July 10, 2020. Full-text: https://doi.org/10.1016/S2352-3026(20)30218-0
Careful comment on these findings. According to the author, the study is a valuable contribution to the knowledge of the coagulation profile of patients with COVID-19 and highlights the established role of routine coagulation tests as predictive variables for mortality and morbidity. However, the question of whether the observed changes in routine coagulation tests are just markers of the severity of illness or whether they show a significant and specific pathophysiology that drives morbidity and mortality in itself is still unanswered.
Moezinia CH, Ji-Xu A, Azari A, et al. Iloprost for COVID-19-related vasculopathy. Lancet Rheumatology July 10, 2020. Full-text: https://doi.org/10.1016/S2665-9913(20)30232-0
Interesting new finding: iloprost as a therapy to mitigate the pathological effects of COVID-19. Iloprost is a prostacyclin receptor agonist that promotes vasodilation of circulatory beds with minimal impact on hemodynamic parameters. It is licensed for the treatment of pulmonary arterial hypertension and is widely used for the management of peripheral vascular disease and digital vasculopathy, including digital ulcers and critical digital ischemia in systemic sclerosis. The authors describe three morbidly obese patients with severe COVID-19 and systemic microvasculopathy who obviously benefitted from its use. Its potential ability to reduce endothelial dysfunction and systemic inflammation could make iloprost a key player in management of COVID-19 vasculopathy.
Ikematsu H, Hayden FG, Kawaguchi K, et al. Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts. NEJM July 8, 2020. Full-text: https://doi.org/10.1056/NEJMoa1915341
How will we deal with influenza next winter? Baloxavir marboxil (baloxavir) is a prodrug of the cap-dependent endonuclease inhibitor baloxavir acid and was approved as a single-dose treatment for uncomplicated influenza A and B in Japan and in the US in 2018. Among 752 household contacts of 545 index patients (96% influenza A) virus infection, the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%).
Uyeki TM. Baloxavir for Postexposure Prophylaxis against Influenza in Households. NEJM July 8, 2020. Full-text: https://doi.org/10.1056/NEJMe2022702
This editorial discusses some caveats of the above trial, including resistance issues. Moreover, 73% of the household contacts received baloxavir or placebo rapidly – within 24 hours after the onset of illness. Last but not least, clinicians are reminded that the primary prevention of influenza is through annual influenza vaccination. We have to be prepared next winter.
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.
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.
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.
Hogan AB, Jewel BL, Sherrard-Smith E, et al. Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study. Lancet July 13, 2020. Full-text: https://doi.org/10.1016/S2214-109X(20)30288-6
The collateral damage is just as great. Using established transmission models, data indicate that in countries with a high burden of malaria, HIV and tuberculosis, COVID-19 related disruptions in care could lead to a loss of life-years of over 5 years, that is of the same order of magnitude as the direct impact from COVID-19. The authors estimate that deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10% due to HIV (mainly due to treatment interruptions), 20% to TB (less timely diagnosis and treatment of new cases), and 36% to malaria (interruption of planned net campaigns), respectively.
Today, 15 July 2020, there will be no Top 10, but the Top 1,000:
COVID Reference Top 10 – Daily Science (390 pages, download)
Here we publish in a single PDF our daily Top 10 papers we have presented ever since COVID Reference’s first edition on 29 March 2020. There is no secret to our procedure: the daily scanning of the literature helps us to stay afloat in the never-ending waves of new publications about SARS-CoV-2 and COVID-19. Many papers discussed in the Top 10 will eventually make it into subsequent editions of COVID Reference.
We dedicate this book to our students. May this selection of approx. 1,000 fine articles and full-text links deepen their understanding of the new coronavirus and prepare them for the challenges ahead.
Stay with us for the next thousand Top 10 papers.
All the best,
Christian Hoffmann & Bernd Sebastian Kamps
Find 22 outstanding papers at https://covidreference.com/outstanding-papers.
- P. S.
We have also updated the Transmission chapter in order to reflect the latest WHO statement on aerosol transmission:
“There have been reported outbreaks of COVID-19 in some closed settings, such as restaurants, nightclubs, places of worship or places of work where people may be shouting, talking, or singing. In these outbreaks, aerosol transmission, particularly in these indoor locations where there are crowded and inadequately ventilated spaces where infected persons spend long periods of time with others, cannot be ruled out.”
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.
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 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% 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%), diarrhoea (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 finding of 10% of patients confirms that the prevalence of GI symptoms at onset “is not negligible”. That’s probably why this has been published in Gut.
Grasselli G, Greco M, Zanella A, et al. Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med July 15, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.3539
If you are at the ICU, it’s 50/50. In this large cohort study of 3,988 critically ill patients, most required invasive mechanical ventilation, and mortality rate was high. In the subgroup of the first 1715 patients, 915 patients died in the hospital for overall hospital mortality of (53.4%).
Gupta S, Hayek SS, Wang W, et al. Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US. JAMA Intern Med July 15, 2020. –Full-text: https://doi.org/10.1001/jamainternmed.2020.3596
But it depends where you are. In this US cohort of 2,215 adults with COVID-19 who were admitted to ICUs at 65 sites, 784 (35.4%) died within 28 days. However, mortality showed an extremely wide variation among hospitals (range, 6.6%-80.8%). Factors associated with death included older age, male sex, obesity, coronary artery disease, cancer, acute organ dysfunction, and, importantly, admission to a hospital with fewer intensive care unit beds. Patients admitted to hospitals with fewer than 50 ICU beds versus at least 100 ICU beds had a higher risk of death (OR 3.28; 95% CI, 2.16-4.99).
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.
Kind request to all authors of scientific papers
This is a kind request to everyone in the scientific community who is currently working on scientific papers on COVID-19, brooding over introductions. It is no longer necessary to emphasize that the “COVID-19 pandemic has to date caused >7 million infections resulting in over 400,000 deaths” and that “following infection with SARS-CoV2, COVID-19 patients can experience mild or even asymptomatic disease, or can present with severe disease requiring hospitalization and mechanical ventilation.” (Science, July 15). And, please, don’t start your paper or your abstract with the COVID-19 pandemic as “a major threat to global health for which there are limited medical countermeasures” (Nature, July 15). More brand-new findings? “The severe acute respiratory syndrome coronavirus 2 emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine” (NEJM, July 15).
Are you kiddin’? We know it. We all know it! We all know it all! On July 16th, Pubmed.gov listed more than 31,000 COVID-19 papers. Almost every paper is (fortunately) freely accessible. We are faced with dozens of important scientific papers every day and our time is limited. So get down to business, folks. Straight to the point, no elaborations. Save yourself cumbersome or scrambled introductions.
Rob Camp, Christian Hoffmann, Bernd Sebastian Kamps
Tan M, He FJ, MacGregor GA. Obesity and covid-19: the role of the food industry. BMJ. 2020 Jun 10;369:m2237. PubMed: https://pubmed.gov/32522740. Full-text: https://doi.org/10.1136/bmj.m2237
Sorry for being 40 days late to present this article published in June. As obesity is being recognized as an independent risk factor for severe illness and death from COVID-19, a reminder of the players involved in the obesity pandemic is always helpful. The authors have a concise message: “Food industries around the world must immediately stop promoting, and governments must force reformulation of, unhealthy foods and drinks.” As food industries won’t strop promoting, governments must regulate them.
Apicella M, Campopiano MC, Mantuano M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol, 17 July 2020. Full-text: https://doi.org/10.1016/S2213-8587(20)30238-2
This review provides an assessment of prognostic factors in patients with diabetes and COVID-19. The poorer prognosis would be the consequence of the syndromic nature of diabetes: hyperglycemia, older age, comorbidities, and in particular hypertension, obesity, and cardiovascular disease. All would contribute to an increased risk.
Mato AR, Roeker LE, Lamanna N, et al. Outcomes of COVID-19 in Patients with CLL: A Multicenter, International Experience. Blood. 2020 Jul 20:blood.2020006965. PubMed: https://pubmed.gov/32688395. Full-text: https://doi.org/10.1182/blood.2020006965
CLL patients have impaired humoral and cellular immune function. The authors describe the first large, disease-specific series in a defined cohort of hematologic cancer patients from 43 international centers. Of 198 CLL patients diagnosed with symptomatic COVID-19, 39% were treatment-naïve (“watch and wait”) while 61% had received at least one CLL-directed therapy. At a median follow-up of 16 days, the overall case fatality rate was 33%, while 25% were still in hospital. Discover differences between “Watch and wait” and treated cohorts with regard to ICU admission, intubation, and mortality. CLL patients are at high risk of death.
Bilaloglu S, Aphinyanaphongs Y, Jones S, et al. Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System. JAMA. Published online July 20, 2020. Full-text: https://doi.org/10.1001/jama.2020.13372
The authors assessed the incidence of, and risk factors for, venous and arterial thrombotic events in patients with COVID-19 in 4 hospitals in New York City. Among 3334 consecutive patients, a thrombotic event occurred in 16.0%. 207 (6.2%) were venous (3.2% PE and 3.9% DVT) and 365 (11.1%) were arterial (1.6% ischemic stroke, 8.9% MI, and 1.0% systemic thromboembolism. All-cause mortality was 24.5% and was higher in those with thrombotic events (43.2% vs 21.0%). D-dimer level at presentation was independently associated with thrombotic events, consistent with an early coagulopathy.
Maringe C, Spicer J, Morris M, et al. The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study. Lancet Oncology, published: July 20, 2020. Full-text: https://doi.org/10.1016/S1470-2045(20)30388-0
During the UK COVID lockdown, cancer screening was suspended, routine diagnostic work deferred, and only urgent symptomatic cases prioritized for diagnostic intervention. The authors estimate the impact of diagnostic delays over a 12-month period from the commencement of physical distancing measures, on March 16, 2020, up to 1, 3, and 5 years after diagnosis. They expect an increase in the number of avoidable cancer as a result of the COVID-19 pandemic:
Breast cancer: 281–344 additional deaths (increase: 7.9–9.6%)
Colorectal cancer: 1445–1563 (15·3–16·6%)
Lung cancer: 1235–1372 (4.8–5.3%)
Oesophageal cancer: 330–342 (5.8–6.0%)
See also the comment by Hamilton W: Cancer diagnostic delay in the COVID-19 era: what happens next? Lancet Oncology, published: July 20, 2020. Full-text: https://doi.org/10.1016/S1470-2045(20)30391-0
Kamrath C, Mönkemöller K, Biester T, et al. Ketoacidosis in Children and Adolescents With Newly Diagnosed Type 1 Diabetes During the COVID-19 Pandemic in Germany. JAMA. Published online July 20, 2020. Full-text: https://doi.org/10.1001/jama.2020.13445
The COVID pandemic has caused people to delay medical care, even for life-threatening conditions. The authors analyzed data of 532 children and adolescents with newly diagnosed type 1 diabetes from 216 German diabetes centers (median age: 9.9 years). Diabetic ketoacidosis was present in 238 patients (44.7%) and severe ketoacidosis in 103 patients (19.4%). During the same period of 2019 and 2018, the frequency of diabetic ketoacidosis was significantly lower (2019: 13.9%; 2018: 12.3%). The incidence of severe diabetic ketoacidosis was also significantly lower (2019: 13.9%; 2018: 12.3% in 2018). Children younger than 6 years had the highest risk.
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 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 pictures.
Yao Z, Chen J, Wang Q, et al. Three Patients with COVID-19 and Pulmonary Tuberculosis, Wuhan, China, January-February 2020. Emerg Infect Dis. 2020 Jul 15;26(11). PubMed: https://pubmed.gov/32667282. Full-text: https://doi.org/10.3201/eid2611.201536
Tham SM, Lim WY, Lee CK, et al. Four Patients with COVID-19 and Tuberculosis, Singapore, April-May 2020. Emerg Infect Dis. 2020 Jul 15;26(11). PubMed: https://pubmed.gov/32667283. Full-text: https://doi.org/10.3201/eid2611.202752
Two papers about three patients with COVID-19 and tuberculosis in Wuhan and four patients in Singapore. Clinicians treating at-risk populations should be aware of possible co-infection with M. tuberculosis and SARS-CoV-2 in patients with atypical radiographic features of COVID-19.
Kon ZN, Smith DE, Chang SH, et al. Extracorporeal Membrane Oxygenation Support in Severe COVID-19. Ann Thorac Surg. 2020 Jul 17:S0003-4975(20)31152-8. PubMed: https://pubmed.gov/32687823. Full-text: https://doi.org/10.1016/j.athoracsur.2020.07.002
The authors describe their institutional practice regarding ECMO support for 27 patients with COVID-19. At the time of paper submission, survival was 96.3% (one death) in over 350 days of total ECMO support. Thirteen patients (48.1%) remained on ECMO support, while 13 patients (48.1%) had been successfully decannulated. Seven patients (25.9%) had been discharged from the hospital while six patients (22.2%) remained in the hospital of which four were on room-air. The authors rightly conclude that the judicious use of ECMO support may be clinically beneficial.
Kansagra Ap, Goyal MS, Hamilton S, Albers GW. Collateral Effect of Covid-19 on Stroke Evaluation in the United States. N Engl J Med 2020; 383:400-401. Full-text: https://doi.org/10.1056/NEJMc2014816
Any decrease in care for patients with ischemic stroke may be consequential because timely treatment may decrease the incidence of disability. The authors compare the mean daily counts per hospital of patients in the prepandemic 29-day epoch from February 1, 2020, through February 29, 2020, with the mean daily counts per hospital of patients in a 14-day epoch during the early pandemic, from March 26, 2020, through April 8, 2020. They found a decrease of approximately 39% in the numbers of patients who received evaluations for acute stroke between two recent epochs in U.S. hospitals. The decrease in the use of stroke imaging from the prepandemic epoch to the early-pandemic epoch was seen across all age, sex, and stroke severity subgroups.
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.