+++ Clinical Manifestation +++

* * * Next update: 24 November. In the meantime, find the global updates at 7 Days. * * *

19 November

Dhawan  R, Gopalan D, Howard L, et al. Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19. Lancet Repiratory Medicine 2020, published 17 October. Full-text: https://doi.org/10.1016/S2213-2600(20)30407-0

The long-term outcomes in survivors of COVID-19 are unknown at present. As pulmonary thrombosis and thromboembolism occur during clinical SARS-CoV-2 infection, the authors propose a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential hemodynamic sequelae that might affect quality of life for a long time.


18 November

Bois MC, Boire NA, Layman AJ, et al. COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart. Circulation. 2020 Nov 16. PubMed: https://pubmed.gov/33197204. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.050754

What are the underlying mechanisms of cardiac complications? This small, but detailed histopathologic, immunohistochemical, ultrastructural and molecular cardiac series of 15 COVID-19 cases showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently had cardiac fibrin microthrombi (12/16), without universal acute ischemic injury. Moreover, myocarditis was present in 33.3% of active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.


Vaira LA, Hopkins C, Sandison A, et al. Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia. J Laryngol Otol. 2020 Nov 16:1-13. PubMed: https://pubmed.gov/33190655. Full-text: https://doi.org/10.1017/S0022215120002455

Interesting case report of a patient who presented with anosmia persisting for more than three months after infection. MRI did not reveal any pathological findings: the olfactory bulb and clefts were of normal volume, without signal anomalies. However, the biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.


Alvarez-Garcia J, Lee S, Gupta A, et al. Prognostic Impact of Prior Heart Failure in Patients Hospitalized With COVID-19. J Am Coll Cardiol. 2020 Nov 17;76(20):2334-2348. PubMed: https://pubmed.gov/33129663. Full-text: https://doi.org/10.1016/j.jacc.2020.09.549

Retrospective analysis of 6439 patients admitted for COVID-19 at 5 hospitals in New York City between February 27 and June 26, 2020. Compared with patients without heart failure (HF), those with previous HF experienced longer length of stay (8 days vs. 6 days; p < 0.001), increased risk of mechanical ventilation (22.8% vs. 11.9%), and mortality (40.0% vs. 24.9%). Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use.

17 November

Coate KC, Cha , Shrestha S. SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 are Expressed in the Microvasculature and Ducts of Human Pancreas but are Not Enriched in β Cells. Cell Metabolism November 13, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.11.006

Isolated reports of new-onset diabetes in COVID-19 cases have led to the hypothesis that SARS-CoV-2 is directly cytotoxic to pancreatic islet β cells. Katie Coate and colleagues show here that it’s not that easy. In pancreatic sections, ACE2 and TMPRSS2 protein (the main cell entry factors) were not detected in β cells from donors with and without diabetes. Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. Contrasting with previous reports, this careful investigation suggests that the interaction of diabetes and SARS-CoV-2 is mediated by systemic inflammation and/or metabolic changes in other organs such as liver, muscle or adipose tissue (and not by a direct infection of β cells in the pancreas).


Shi Z, de Vries HJ, Vlaar AP, et al. Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers. JAMA Intern Med November 16, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.6278

This study focused on the diaphragm, the main muscle of respiration. Consecutive diaphragm muscle specimens from 26 deceased COVID-19 patients were compared with autopsy diaphragm specimens of 8 patients who had been critically ill without COVID-19. There was an increased expression of genes involved in fibrosis and histological evidence for the development of fibrosis in the diaphragm. Of note, this myopathic phenotype was distinctly different from that of control ICU patients, with comparable duration of mechanical ventilation and ICU length of stay. It is hypothesized that severe myopathy may lead to diaphragm weakness and might contribute to ventilator weaning failure, persistent dyspnea, and fatigue in COVID-19 survivors.


Miller DG, Piesron L, Doernberg S. The Role of Medical Students During the COVID-19 Pandemic. Annals Int Med 2020, November 17. Full-text: https://doi.org/10.7326/L20-1195

Interesting discussion about in-person medical student involvement during the COVID-19 pandemic. Some authors argue for it, others against it. Both sides have good arguments.


16 September

Chopra C, Flanders Sa, O’Malley M, et al. Sixty-Day Outcomes Among Patients Hospitalized With COVID-19. Annals Int Med 11 November 2020. Full-text: https://doi.org/10.7326/M20-5661

The toll of COVID-19 extends well beyond hospitalization. In this cohort study of 1648 patients with COVID-19 admitted to 38 hospitals in Michigan, 398 (24%) died during hospitalization and 1250 (76%) survived. Of these, 975 (78%) went home whereas 158 (13%) were discharged to a skilled nursing or rehabilitation facility. By 60 days after discharge, an additional 84 patients (7% of hospital survivors and 10% of ICU-treated hospital survivors) had died. Within 60 days of discharge, 189 patients (15% of hospital survivors) were re-hospitalized. Of patients alive 60 days after discharge, 488 (41.8%) completed a telephone survey. For most patients who survived, ongoing morbidity, including the inability to return to normal activities, physical and emotional symptoms, and financial loss, was common.


Griffith GJ, Morris TT, Tudball MJ, et al. Collider bias undermines our understanding of COVID-19 disease risk and severity. Nat Commun 11, 5749 (2020). Full-text: https://doi.org/10.1038/s41467-020-19478-2

Numerous observational studies have attempted to identify risk factors for infection with SARS-CoV-2 and COVID-19 disease outcomes. Studies have used datasets sampled from patients admitted to hospital, people tested for active infection, or people who volunteered to participate. Here, Gareth J. Griffith and colleagues from Bristol highlight the challenge of interpreting observational evidence from such non-representative samples. Read how the collider bias (a variable that is influenced by two other variables, for example when a risk factor and an outcome both affect the likelihood of being sampled) can have a dramatic impact on the results and what approaches are available to explore and mitigate this problem.


15 September

Liao X, Wang Y, He Z, et al. Three-month pulmonary function and radiological outcomes in COVID-19 survivors: a longitudinal patient cohort study. Open Forum Infectious Diseases, 14 November 2020. Full-text: https://doi.org/10.1093/ofid/ofaa540

More on “Long COVID-19”. In this study, 172 survivors (33 with severe COVID-19) underwent high resolution CT of the thorax and pulmonary function tests at three months after hospital discharge. An abnormal pulmonary function was found in 11 (6%), and abnormal small airway function (FEF25-75%) in 12 (7%) patients. Obstructive and restrictive ventilation impairment was observed in six (3.5%) patients each. Lung function parameters did not differ between non-severe and severe cases. Of 142 CT scans, 122 (86%) showed residual CT abnormalities and 52 (37%) showed chronic and fibrotic changes.


14 November

Choi B, Choudhary MC, Regan J, et al. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. N Engl J Med 2020, published 11 November. Full-text: https://doi.org/10.1056/NEJMc2031364

Under special circumstances, for example in an immunocompromised state, SARS-CoV-2 has the potential for persistent infection and accelerated viral evolution. This is the result of a case report by Manuela Cernadas, Jonathan Li, Bina Choi and colleagues who describe the clinical course of a 45-year-old man with long-standing antiphospholipid syndrome, an autoimmune disorder. Before his death five months after the initial COVID-19 diagnosis, SARS-CoV-2 infection subsided and came back twice.


Wong CKH, Wong JY, Tang EHM, et al. Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis. Sci Rep 10, 19765 (2020). Full-text: https://doi.org/10.1038/s41598-020-74988-9

Meta-analysis of 76 studies published from January-March 2020 on clinical presentation, laboratory findings and treatments of COVID-19 patients, accounting for a total of 11,028 COVID-19 patients. The most common co-morbidities were hypertension (18%), followed by cardiovascular disease (12%) and diabetes (10%). The most frequently identified symptoms were fever (72%) and cough (56%). Notably, 62% and 20% of in-patients received oxygen therapy and non-invasive mechanical ventilation, respectively. In this review, radiological findings of SARS-CoV-2 pneumonia were non-specific.


13 November

Meppiel E, Peiffer-Smadja N, Maury A, et al. Neurological manifestations associated with COVID-19: a multicentric registry. Clin Microbiol Infect 2020, published 12 November. Full-text: https://doi.org/10.1016/j.cmi.2020.11.005

Clinical spectrum and outcomes of neurological manifestations associated with SARS-CoV-2 infection may be broad and heterogeneous, suggesting different underlying pathogenic processes. This is the conclusion of a French multicenter study describing 222 patients. The most common neurological diseases were COVID-19 associated encephalopathy (30,2%), acute ischemic cerebrovascular syndrome (25,7%), encephalitis (9,5%), and Guillain-Barré Syndrome (6,8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19 associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré Syndrome.


10 November

Lavery AM, Preston LE, Ko JY, et al. Characteristics of Hospitalized COVID-19 Patients Discharged and Experiencing Same-Hospital Readmission — United States, March–August 2020. MMWR Morb Mortal Wkly Rep. ePub: 9 November 2020. Full-text:  http://dx.doi.org/10.15585/mmwr.mm6945e2

Who will be re-admitted? In a cohort of 106,543 patients discharged after an index COVID-19 hospitalization, 9% experienced at least one readmission to the same hospital within 2 months of discharge. Multiple readmissions occurred in 1.6% of patients. Not very surprising: risk factors for readmission included age ≥ 65 years, presence of certain chronic conditions (chronic obstructive pulmonary disease, heart failure, diabetes with chronic complications, chronic kidney disease, and obesity), hospitalization within the 3 months preceding the first COVID-19 hospitalization, and discharge to a skilled nursing facility or with home health care.


9 November

Avanzato VA, Matson MJ, Seifert SN, et al. Case Study: Prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised cancer patient. Cell November 04, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.10.049

Immunocompromised patients may shed infectious virus for longer durations than previously recognized: Victoria Avanzato and colleagues describe an interesting case of a female immunocompromised patient with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Shedding of infectious SARS-CoV-2 was observed up to 70 days.

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6 November

Santos-Ferreira D, Tomás R, Dores H. Return-to-Play Guidelines for Athletes After COVID-19 Infection. JAMA Cardiol. November 4, 2020. Full-text: https://doi.org/10.1001/jamacardio.2020.5345

What to do with athletes after recovery? The clinical implications of asymptomatic to mild COVID-19 still remain undetermined. Pulmonary and cardiac fibrosis are potentially the most relevant for athletes, which may lead to reduced lung capacity or cardiac dysfunction, malignant arrhythmias, and sudden death. Complications from the disease must be excluded prior to returning to play. According to the authors, those with suspected or confirmed COVID-19 (including mild or complicated disease) or presenting with suggestive signs or symptoms should undergo additional investigations according to presentation and disease severity. These may include blood tests, electrocardiography, echocardiography, 24-hour and/or 48-hour Holter monitoring, exercise testing, or lung function tests.


Smilowitz NR, Jethani N, Chen J, et al. Myocardial Injury in Adults Hospitalized with COVID-19. Circulation 5 Nov 2020. Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.050434

Nathaniel R. Smilowitz and colleagues have analyzed myocardial injury at admission and during hospitalization in a large cohort of 2163 patients with COVID-19 from a high-volume health care system in New York. Nearly a third (32%) had myocardial injury at presentation, and nearly half had injury detected during the course of their hospitalization. Regardless of when it was first detected, myocardial injury was associated with increased odds of mortality and critical illness, with higher cardiac Troponin (cTn) measurements associated with worse outcomes.


3 November

Zhong P, Xu J, Yang D, et al. COVID-19-associated gastrointestinal and liver injury: clinical features and potential mechanisms. Sig Transduct Target Ther 5, 256 (2020). Full-text: https://doi.org/10.1038/s41392-020-00373-7

Besides common respiratory symptoms, some patients with COVID-19 experience gastrointestinal symptoms, such as diarrhea, nausea, vomiting, and loss of appetite. In this review, Yangbai Sun, Peijie Zhong and colleagues highlight the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19.


2 November

Gandhi RT, Lynch JB, del Rio C. Mild or Moderate Covid-19. N Engl J Med, October 29, 2020; 383:1757-1766. Full-text: https://doi.org/10.1056/NEJMcp2009249

Brief overview for clinicians. In patients with moderate disease, dexamethasone is not efficacious (and may be harmful) and data are insufficient to recommend for or against routine use of remdesivir. Efforts center on personal protective equipment for health care workers, social distancing, and testing.


Giustino G, Croft LB, Stefanini GG, et al. Characterization of Myocardial Injury in Patients With COVID-19. J Am Coll Cardiol. 2020 Nov 3;76(18):2043-2055. PubMed: https://pubmed.gov/33121710. Full-text: https://doi.org/10.1016/j.jacc.2020.08.069

This multicenter cohort study (7 hospitals in New York City and Milan) analyzed hospitalized COVID-19 patients who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. Overall, myocardial injury was observed in 190 patients (62.3%). Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities.


1 November

Hoffmann C, Wolf E. The Low Case Fatality Rate of COVID-19 in Hong Kong Could Be Deceptive. Clin Infect Dis. 2020 Oct 29:ciaa1676. PubMed: https://pubmed.gov/33119056 . Full-text: https://doi.org/10.1093/cid/ciaa1676

Last Monday, we published data from the 20 most affected European countries and the USA and Canada, showing that during the first wave of the pandemic, the variance of crude CFR of COVID-19 was predominantly (80-96%) determined by the proportion of older individuals who are diagnosed with SARS-CoV-2 (Hoffmann 2020).

Here we show that our model might apply to other countries. In Hong Kong, for example, a very low CFR of only 0.4% has been reported during the first weeks (Lui GC 2000). In contrast to the authors, we believe that this was mainly due to the low number of older persons among the confirmed SARS-CoV-2 cases. We also show that the overall CFR in Hong Kong has increased since then, paralleling the increasing proportion of older persons among confirmed cases. Thanks to the incredible speed of Clinical Infectious Diseases’ publishing policies (contrasting many other journals), the authors from Hong Kong have been already able to respond (in some points they agree, in other points they don’t). Please read the discussion (Lui GC 2000).

Why is this important? In many countries facing a low CFR during the first wave, there is a widespread feeling that this was mainly due to a good health care system such as ICU or testing capacities. We believe that this perception can be deceptive and that the picture in these countries will change immediately when more elderly people are infected.

Hoffmann C, Wolf E. Older age groups and country-specific case fatality rates of COVID-19 in Europe, USA and Canada. Infection. 2020 Oct 24:1-6. PubMed: https://pubmed.gov/33098532 . Full-text: https://doi.org/10.1007/s15010-020-01538-w

Lui GC, Yip TC, Wong VW, et al. Significantly Lower Case-fatality Ratio of Coronavirus Disease 2019 (COVID-19) than Severe Acute Respiratory Syndrome (SARS) in Hong Kong-A Territory-Wide Cohort Study. Clin Infect Dis. 2020 Oct 1:ciaa1187. PubMed: https://pubmed.gov/33005933. Full-text: https://doi.org/10.1093/cid/ciaa1187

Lui CG, Yip TC, Hui D, et al. Reply to Hoffmann and Wolf. Clinical Infectious Diseases, October 29, ciaa1678, https://doi.org/10.1093/cid/ciaa1678. PDF: xxx


Lim ZJ, Subramaniam A, Reddy MP, et al. Case Fatality Rates for COVID-19 Patients Requiring Invasive Mechanical Ventilation: A Meta-analysis. Am J Respir Crit Care Med. 2020 Oct 29. PubMed: https://pubmed.gov/33119402 . Full-text: https://doi.org/10.1164/rccm.202006-2405OC

Definitive hospital outcome on 13,120 patients receiving invasive mechanical ventilation. Among studies where age-stratified CFR was available, pooled CFR estimates ranged from 47.9% (95% CI 46.4-49.4%) in younger patients (age ≤40) to 84.4% (95% CI 83.3-85.4) in older patients (age >80). CFR was also higher in early COVID-19 epicenters.


Prieto-Alhambra D, Balló E, Mora N, et al. Filling the gaps in the characterization of the clinical management of COVID-19: 30-day hospital admission and fatality rates in a cohort of 118 150 cases diagnosed in outpatient settings in Spain. International Journal of Epidemiology, October 29, 2020, dyaa190. Full-text: https://doi.org/10.1093/ije/dyaa190

Filling the missing link in the natural history of COVID-19, from first (usually milder) symptoms to hospitalization and/or death, the authors characterized a huge number of COVID-19 patients at the time at which they were diagnosed in outpatient settings and estimated 30-day hospital admission and fatality rates. In the month after diagnosis, 14.8% (14.6–15.0) were hospitalized, with a greater proportion of men and older people, peaking at age 75–84 years. Thirty-day fatality was 3.5%, higher in men, increasing with age and highest in those residing in nursing homes (24.5%).


Kim T, Roslin M, Wang JJ, et al. Body Mass Index as a Risk Factor for Clinical Outcomes in Patients Hospitalized with COVID-19 in New York. Obesity (Silver Spring). 2020 Oct 31. PubMed: https://pubmed.gov/33128848 . Full-text: https://doi.org/10.1002/oby.23076

Risk factor obesity. In total, 10,861 COVID‐19 patients admitted to the Northwell Health system hospitals during March and April, were classified according to their BMI: underweight (2%), normal (only 23%!), overweight (38%), obesity class I (22%), II (9%), and III (7%). Patients who were overweight (OR=1.27), obesity class I (OR=1.48), obesity class II (OR=1.89), and obesity class III (OR=2.31) had increased risk of requiring invasive mechanical ventilation. Overall, underweight and obesity classes II and III were statistically associated with death (OR=1.25-1.61). However, once mechanically ventilated, all patients regardless of BMI had similar odds of death.


30 October

Fajnzylber J, Regan J, Coxen K, et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun 11, 5493 (2020). https://doi.org/10.1038/s41467-020-19057-5

SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. This is the result of a study by Jonathan Li, Jesse Fajnzylber and colleagues who report SARS-CoV-2 respiratory tract, plasma, and urine viral loads of 235 participants who were either hospitalized with COVID-19 (n=88), evaluated as symptomatic outpatients (n=94), or had recovered from COVID-19 disease (n=53). The prevalence of SARS-CoV-2 plasma viremia in hospitalized individuals with severe disease was relatively high, but plasma viremia was also detected in symptomatic non-hospitalized participants. Compared to individuals who were discharged from the hospital, those who eventually died had significantly higher levels of plasma viremia at the time of initial sampling (median plasma viral load 1.0 vs 2.0 log10 RNA copies/mL). For hospitalized individuals with initial detectable viremia, 32% died vs. 8% of those without initial viremia (odds ratio (OR) 5.5).


An C, Lim H, Kim D, et al. Machine learning prediction for mortality of patients diagnosed with COVID-19: a nationwide Korean cohort study. Sci Rep 10, 18716 (2020). Full-text: https://doi.org/10.1038/s41598-020-75767-2

At the height of pandemic waves, healthcare services may be overwhelmed by huge numbers of patients. Here, the authors propose a prediction model which might be helpful for the quick triage of patients without having to wait for the results of additional tests such as laboratory or radiologic studies. They demonstrate that machine learning models utilizing sociodemographic characteristics and medical history might accurately predict the prognosis of COVID-19 patients after diagnosis. Their models predicted not only the final outcome (i.e., mortality vs. recovery) but also early mortality (i.e., 14- or 30-day mortality).


28 October

Brandén M, Aradhya S, Kolk M, et al. Residential context and COVID-19 mortality among adults aged 70 years and older in Stockholm: a population-based, observational study using individual-level data. Lancet Healthy Longevity 2020, published 27 October. Full-text: https://doi.org/10.1016/S2666-7568(20)30016-7

Living in a care home is associated with increased mortality – we knew that. Living in neighbourhoods with high population density (≥5000 individuals per km2) is associated with higher COVID-19 mortality (1·7; 1·1–2·4) compared with living in least densely populated neighbourhoods (0 to <150 individuals per km2) – we knew that, too. Living with someone of working age (<66 years), when compared with living in a household with individuals aged 66 years or older, was associated with increased COVID-19 mortality (hazard ratio 1·6; 95% CI 1·3–2·0). We imagined that. It was reported by Maria Brandén and colleagues after analyzing 274,712 individuals aged 70 years or older and residing in Stockholm. See also the comment by Roxby AC, Gure TR: Lessons from Sweden: where can older adults shelter from COVID-19? Lancet Healthy Longevity 2020, published 27 October. Full-text: https://doi.org/10.1016/S2666-7568(20)30035-0


22 October

Clift AK, Coupland CAC, Keogh RH, Hemingway H, Hippisley-Cox J. COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study Of 8 Million Adults. Ann Intern Med. 2020 Oct 21. PubMed: https://pubmed.gov/33085509. Full-text: https://doi.org/10.7326/M20-4986

Persons with Down syndrome seem to be at an increased risk for COVID-19–related hospitalization and death. This is the result of an analysis of individual-level data in a cohort study of 8.26 million adults in the UK. The authors estimated a 4-fold increased risk for COVID-19–related hospitalization and a 10-fold increased risk for COVID-19–related death.


Car J, Koh GCH, Foong PS, Wang J. Video consultations in primary and specialist care during the covid-19 pandemic and beyond. BMJ 2020; 371. Full-text: https://doi.org/10.1136/bmj.m3945

At the start of the pandemic, many GPs and specialists turned to video consultations to reduce patient flow through healthcare facilities and limit infectious exposures. What was your experience? Josip Car and colleagues give you a grand tour of video consultations in the COVID-19 era:  how to start, how to prepare the patients for the consultation, suggestions for a remote physical examination, and how to switch from a video to a telephone or in-person consultation, depending on technical, patient, or clinical factors. A must-read for GPs.


21 October

Clift AK, Keogh RH, Diaz-Ordaz K, et al. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. BMJ 2020, published 20 October. Full-text: https://doi.org/10.1136/bmj.m3731

Julia Hippisley-Cox, Ash Clift and colleagues present a new risk tool to predict a person’s risk of being admitted to hospital and dying from COVID-19. They used data from 6 million patients over a 97 day period (24 January to 30 April 2020), and a further 2.2 million patients to validate its performance over two separate time periods (24 January to 30 April 2020 and 1 May to 30 June 2020). People in the top 5% for predicted risk of death accounted for 76% of COVID-19 deaths within the 97-day study period while people in the top 20% accounted for 94% of COVID-19 deaths. We are now waiting for the model to be freely available on the internet.

See also the comment by Matthew Sperrin: Prediction models for covid-19 outcomes. BMJ 2020, published 20 October. Full-text: https://doi.org/10.1136/bmj.m3777


di Filippo L, Formenti AM, Doga M, et al. Radiological Thoracic Vertebral Fractures are highly prevalent in COVID-19 and predict disease outcomes. J Clin Endocrinol Metabol 2020, published 21 October. Full-text: https://doi.org/10.1210/clinem/dgaa738

In this retrospective cohort study from a tertiary health-care hospital in Northern Italy, 114 SARS-CoV-2 positive patients were included. Thoracic vertebral fractures (VF) were detected in 41 patients (36%). Patients with VFs required more frequently a non-invasive mechanical ventilation compared to those without VFs (p=0.02). Mortality was 22% in VFs+ group and 10% in VFs- group (p=0.07). In particular mortality was higher in patients with severe VFs compared to those with moderate and mild VFs (p=0.04). The authors conclude that VF might be a useful and easy to measure clinical marker of fragility and poor prognosis and suggest that morphometric thoracic vertebral evaluation should be performed in all suspected COVID-19 patients undergoing a chest X-rays.


Hudowenz O, Klemm P, Lange U, et al. Case report of severe PCR-confirmed COVID-19 myocarditis in a European patient manifesting in mid January 2020. European Heart Journal – Case Reports. Full-text:  https://doi.org/10.1093/ehjcr/ytaa286

A positive polymerase chain reaction (PCR) testing of SARS-CoV-2 in heart specimens. The authors present a case of severe COVID-19 myocarditis manifesting in mid-January 2020. Primarily suspected of being related to small-vessel vasculitis, the case was later revised to COVID-associated disease when the patient reported a history of travel to Tyrol. Consequently, PCR testing resulted positive in a previously obtained heart specimen. The immunosuppressive treatment was discontinued. During a follow-up visit at the end of April, the patient’s recovery was stable.


20 October

Yang W, Kandula S, Huynh M, et al. Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis. Lancet Infect Dis 2020, published 19 October. Full-text: https://doi.org/10.1016/S1473-3099(20)30769-6

The infection-fatality risk (IFR) is the risk of death among all infected individuals including those with asymptomatic and mild infections. Here, Wan Yang and colleagues report the outcome of the SARS-CoV-2 infection during the first epidemic wave in in New York City. They found an overall IFR of 1.39%. Age was the all-important factor: 25–44 years: 0.11%; 45–64 years: 0.94%; 65-74 years: 4.9%; 75 years and older: 14.2%. The sample size reported y the authors is impressive: 205 639 people with laboratory-confirmed SARS-CoV-2 infection 2 and 21 447 confirmed and probable COVID-19-related deaths.


19 October

Pimenoff VN, Elfström M, Baussano I et al. Estimating total excess mortality during a COVID-19 outbreak in Stockholm, Sweden. Clinical Infectious Diseases. Full-text: https://doi.org/10.1093/cid/ciaa1593

Ville Pimenoff estimated that since January, the  accumulated  excess morality  in  the  Stockholm  region  in  week  18  was  still  +23%  compared  with  the  average over the previous ten years. Of note, comparison  with  the  number  of  reported  COVID-19-related deaths in the 5-weeks peak period of the outbreak found that 26% of the excess mortality during the COVID-19 epidemic was not recognized as COVID-19-related, neither by public  health  data  nor  by  the  regional  morgue.


Lu QB , Zhang Y, Liu MJ , et al. Epidemiological parameters of COVID-19 and its implication for infectivity among patients in China, 1 January to 11 February 2020. Euro Surveill. 2020;25(40). Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.40.2000250

Using a large database of >2000 COVID-19 cases and potential transmission pairs of cases, the authors estimate the median incubation period to be 7.2 (95% confidence interval: 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007).


18 October

Kontis V, Bennett JE, Rashid T, et al. Magnitude, demographics and dynamics of the effect of the first wave of the COVID-19 pandemic on all-cause mortality in 21 industrialized countries. Nat Med (2020). Full-text: https://doi.org/10.1038/s41591-020-1112-0

The total death toll for the first wave of the COVID-19 pandemic in for 21 industrialized countries (without US, Germany). England and Wales and Spain experienced the largest effect: ~100 excess deaths per 100,000 people, equivalent to a 37% (30–44%) relative increase in England and Wales and 38% (31–45%) in Spain.


Bilinski A, Emanuel EJ. COVID-19 and Excess All-Cause Mortality in the US and 18 Comparison Countries. JAMA  October 12, 2020. Full-text: https://doi.org/10.1001/jama.2020.20717

Alyssa Bilinski and Ezekiel Emanuel have compared 14 countries with all-cause mortality data, finding similar patterns. In countries with moderate COVID-19 mortality, excess all-cause mortality remained negligible throughout the pandemic. In countries with high COVID-19 mortality, excess all-cause mortality reached as high as 102/100 000 in Spain, while in the US it was 72/100 000. However, since May, excess all-cause mortality was higher in the US than in all high-mortality countries, may be due to several factors, including weak public health infrastructure and a decentralized, inconsistent US response to the pandemic.


Gold JA, Rossen LM, Ahmad FB, et al. Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19 — United States, May–August 2020. MMWR Morb Mortal Wkly Rep. ePub: 16 October 2020. Full-text: http://dx.doi.org/10.15585/mmwr.mm6942e1

This report provides information on how demographic and geographic factors have changed among COVID-19–associated deaths during May–August 2020. Of 114,411 COVID-19–associated deaths, 51% of decedents were non-Hispanic White, 24% were Hispanic or Latino (Hispanic), and 19% were non-Hispanic Black. The percentage of Hispanic decedents increased from 16.3% in May to 26.4% in August. Data suggest that the geographic shift from the Northeast to the South and West alone does not entirely account for this increase.


Mascitti H, Bonsang B, Dinh A, et al. Clinical cutaneous features of patients infected with SARS-CoV-2 hospitalized for pneumonia: a cross-sectional study. Open Forum Infectious Diseases, 18 October 2020. Full-text: https://doi.org/10.1093/ofid/ofaa394

Various dermatological signs in 59 COVID-19 patients, being a macular rash the most frequent. All cutaneous features could be related to a vascular leak process.


8 October

Liotta EM, Batra A, Clark JR, et al. Frequent neurologic manifestations and encephalopathy-associated morbidity in Covid-19 patients. Ann Clin Transl Neurol. 2020 Oct 5. PubMed: https://pubmed.gov/33016619. Full-text: https://doi.org/10.1002/acn3.51210

Is encephalopathy independently associated with higher mortality in hospitalized patients with COVID-19? That’s the conclusion of a study of 509 consecutive patients admitted within a hospital network in Chicago between 5 March and 6 April 2020. The increased mortality, independent of respiratory severity, parallels previous reports about sepsis‐associated encephalopathy and delirium‐associated mortality. The authors recognize the limitations of a retrospective study. Keep an eye on the subject.





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