Top 10: May 19

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By Christian Hoffmann &
Bernd S. Kamps

19 May

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First, travel to Nembro in the Northern Italian Province of Bergamo, a city of 11,500. Discover that from January 1 until April 4, 2020, 175 people older than 64 died. For comparison: over the same time period in the years 2015 to 2019, a mean of 36 individuals of the same age died (see Table 1). Most deaths in 2020 occurred between March 1 and April 4. From the outbreak onset until 11 April 2020, only 85 confirmed deaths from COVID-19 were recorded. The authors conclude that the full impact of the COVID-19 pandemic can only be assessed after careful comparison of all-cause mortality in 2020 vs the preceding years.

Afterwards, go to Lyon and determine the prevalence of obesity among adult inpatients with COVID-19; present a detailed description of existing SARS-CoV-2 serology assays at your weekly journal club; analyze 26 studies to learn more about the duration of fecal viral shedding after a negative nasopharyngeal swab; and test 290 serum samples from patients with rheumatoid arthritis, systemic lupus erythematosus, and Sjogren’s syndrome, for cross-reactivity against SARS-CoV-2 IgG and IgM antibodies.

Finally, describe neurologically devastating intra-parenchymal hemorrhage in two patients on extracorporeal membrane oxygenation; discuss with your colleagues a review about psychiatric and neuropsychiatric presentations associated with severe COVID-19; write a review of the literature on thromboembolic events associated with COVID-19; and while awaiting the results of several ongoing randomized controlled trials, present the possible role of favipiravir in the treatment of SARS-CoV-2 infection.



Krammer F, Simon V. Serology assays to manage COVID-19. Science 15 May 2020. Full-text:

Nice overview on different platforms, including binding assays such as enzyme-linked immunosorbent assays (ELISAs), lateral flow assays, or Western blot–based assays. In addition, functional assays that test for virus neutralization, enzyme inhibition, or bactericidal assays can also inform on antibody-mediated immune responses. Many caveats and open questions with regard to antibody testing are also discussed.


Teng J, Dai J, Su Y, et al. Detection of IgM and IgG antibodies against SARS-CoV-2 in patients with autoimmune diseases. Lancet Rheumatology 2020, May 18. Full-text:

No cross-reactivity between autoantibodies and SARS-CoV-2 antibodies: in 290 older serum samples from patients with rheumatoid arthritis, systemic lupus erythematosus, and Sjogren’s syndrome, no IgG and IgM antibodies against SARS-CoV-2 were detected.


Lv H, Wu, NC, Tsang OT, et al. Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections. Open Access Published: May 17, 2020. Full-text:

While cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the two live SARS viruses may be rare, indicating the presence of a non-neutralizing antibody response to conserved epitopes in the spike.


Gupta S, Parker J, Smits S, Underwood J, Dolwani S. Persistent viral shedding of SARS-CoV-2 in faeces – a rapid review. Colorectal Dis. 2020 May 17. PubMed: Full-text:

Combining study results of 26 studies, 54% of those patients tested for fecal RNA were positive. Duration of fecal viral shedding ranged from 1 to 33 days after a negative nasopharyngeal swab. Evidence is still insufficient to suggest that COVID-19 is transmitted via fecally shed virus.



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:

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:

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:

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.


Severe COVID-19

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:

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: Full-text:

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.



Coomes EA, Haghbayan H. Favipiravir, an antiviral for COVID-19? J Antimicrob Chemother. 2020 May 17. pii: 5838326. PubMed: Full-text:

Why not favipiravir for COVID-19? This purine nucleoside analogue acts as a competitive inhibitor of RNA-dependent RNA polymerase and can be given orally (in contrast to remdesivir, another RdRp inhibitor). Authors give a brief overview on clinical studies. The results of several ongoing randomized controlled trials are eagerly awaited.