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Top 10: October 2

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By Christian Hoffmann &
Bernd S. Kamps

2 October

Epidemiology

Buonanno P, Galletta S, Puca M, et al. Estimating the severity of COVID-19: Evidence from the Italian epicentre.  PLOS October 1, 2020. Full-text: https://doi.org/10.1371/journal.pone.0239569

A tentative estimate of the number of deaths either directly or indirectly associated with COVID-19 as well as the total number of persons infected. The findings by Paola Buonanno and colleagues suggest that the reported number of deaths attributable to COVID-19 identified by public authorities accounts only for one half of the observed excess mortality between March 2020 and previous years.

 

Virology

Cheng MH, Zhang S, Porritt RA, et al. Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation. PNAS first published September 28, 2020. Full-text: https://doi.org/10.1073/pnas.2010722117

Mary Hongying Cheng and colleagues from Pittsburgh show that SARS-CoV-2 spike contains sequence and structure motifs highly similar to those of a bacterial superantigen and may directly bind T cell receptors. They also report a skewed T cell receptor repertoire in COVID-19 patients with severe hyperinflammation, in support of such a superantigenic effect. Notably, the superantigen-like motif is not present in other SARS family coronaviruses, which may explain the unique potential for SARS-CoV-2 to cause both MIS-C and the cytokine storm observed in adult COVID-19.

 

Pathogenesis

Zeberg H, Pääbo S. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature September 30, 2020. Full-text: https://doi.org/10.1038/s41586-020-2818-3

Recently, a new dataset was released from the COVID-19 Host Genetics Initiative where the region on chromosome 3 is the only region significantly associated with severe COVID-19 at the genome-wide level. The risk variant in this region confers an odds ratio for requiring hospitalization of 1.6 (95% confidence interval: 1.42-1.79). The genetic variants which are most associated with severe COVID-19 on chromosome 3 are all in high linkage disequilibrium, i.e. they are all strongly associated with each other in the population (Ref).  Here, the authors show that the risk is conferred by a genomic segment of ~50 kb that is inherited from Neanderthals and is carried by ~50% of people in South Asia and ~16% of people in Europe today.

COVID-19 Host Genetics Initiative. The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur J Hum Genet. 2020 Jun;28(6):715-718. PubMed: https://pubmed.gov/32404885. Full-text: https://doi.org/10.1038/s41431-020-0636-6

 

Transmission

Freedman DO, Wilder-Smith A. In-flight Transmission of SARS-CoV-2: a review of the attack rates and available data on the efficacy of face masks. Journal of Travel Medicine September 25. Full-text: https://doi.org/10.1093/jtm/taaa178.

Review of outbreaks during flights. According to the authors, the absence of large numbers of confirmed and published in-flight transmissions of SARS-CoV is encouraging but not definitive evidence that fliers are safe. At present, based on circumstantial data, strict use of masks appears to be protective. Structured prospective studies to quantitate transmission risk on flight with rigid masking protocols are now most pressing.

 

Diagnostics

Perreault J, FournierMJ, Beaudoin-Bussières G, et al. Waning of SARS-CoV-2 RBD antibodies in longitudinal convalescent plasma samples within four months after symptom onset. Blood October 1, 2020. Full-text: https://doi.org/10.1182/blood.2020008367

Josée Perreault and colleagues from Québec, Canada have performed a longitudinal analysis of the anti-RBD antibody response in 15 CCP donors (11 males, 4 females, median age of 56 years, no donor was hospitalized) who donated at least four times, during a time interval after symptom onset ranging from 33-77 days for the first donation to 66-114 days for the last donation. A decrease in anti-RBD antibody level between first and last donation was observed for all donors.

 

Ziegler K, Steininger P, Ziegler R, et al. SARS-CoV-2 samples may escape detection because of a single point mutation in the N gene. Euro Surveill. 2020;25(39). Full-text: https://doi.org/10.2807/1560-7917.ES.2020.25.39.2001650

Katharina Ziegler and colleagues found that a single nucleotide polymorphism (SNP) in the nucleoprotein gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a patient interfered with detection in a widely used commercial assay. Some 0.2% of the isolates in the EpiCoV database contain this SNP. Although SARS-CoV-2 was still detected by the other probe in the assay, this underlines the necessity of targeting two independent essential regions of a pathogen for reliable detection.

 

Sullivan CB, Schwalje AT, Jensen M, et al. Cerebrospinal Fluid Leak After Nasal Swab Testing for Coronavirus Disease 2019. JAMA Otolaryngol Head Neck Surg. October 1, 2020. Full-text: https://doi.org/10.1001/jamaoto.2020.3579

Christopher Blake Sullivan describes a case of a cerebrospinal fluid (CSF) leak after nasal testing for COVID-19. After nasal COVID-19 testing for an elective hernia repair, a woman in her 40s presented shortly after with unilateral rhinorrhea, headache, and vomiting. Of note, the patient had an undiagnosed skull base defect at the fovea ethmoidalis that was present on imaging dating back to 2017. The authors therefore speculate that the swab itself did not result in a violation of the bony skull base, but rather the invasive test caused trauma to the patient’s pre-existing encephalocele. However, adverse events may still occur owing to complex and delicate anatomy.

 

Clinical

Alvarado GR, Pierson BC, Teemer ES, et al. Symptom Characterization and Outcomes of Sailors in Isolation After a COVID-19 Outbreak on a US Aircraft Carrier. JAMA Netw Open. October 1, 2020. 2020;3(10):e2020981. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.20981

The US Army Public Health COVID-19 Task Force describes the results of an independent investigation of the shore-based USS Theodore Roosevelt outbreak response. Of 4,085 sailors who disembarked, 736 had a diagnosis of SARS-CoV-2 (median age, 25 years; interquartile range, 22-31 years; 78% male]. Of these, 590 sailors (80.2%) were characterized as symptomatic, with a median symptom duration of 7 days (interquartile range, 5-11 days) and 146 sailors (19.8%) remained asymptomatic for the duration of the study period. With regard to clinical outcomes, 729 sailors remained in outpatient isolation, 6 were hospitalized, and 1 (a “senior listed member in his 40s”) died during the study period.

 

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

Among a cohort of the first 1013 COVID-19 patients (mean age, 38.4 years; 53.9% male) diagnosed from 23 January to 14 April 2020 in Hong Kong, the CFR was 0.4%, and 5% had ICU admission or death within 30 days of hospital admission. Age and diabetes were associated with worse outcomes, whereas antiviral treatments were not.

 

Treatment

Burki TK. Completion of clinical trials in light of COVID-19. Lancet Resp Med  October 01, 2020. Full-text: https://doi.org/10.1016/S2213-2600(20)30460-4

Some thoughts on how running randomized trials at the same time as dealing with large numbers of critically ill patients. No small task, but “we have to give the same urgency to research on COVID-19 as we do to the clinical need.”

 

Society

Another piece of fake news just to stay in the news? After the April speculations about “injecting” “disinfectant” to cure COVID-19, a fake president now reports a SARS-CoV-2 infection of himself and his spouse. How to believe those who produce more fake than truth? ICU pictures might help convince us.

 

Spanish

If you read Spanish, read Llaneras K. Se superan las 100 muertes al día y un debate sigue ausente: ¿cuántas son demasiadas? El País 2020, published 2 October. Full-text: https://elpais.com/politica/2020/10/01/actualidad/1601543892_815336.html

La saturación de las UCI es un problema. Pero no olvidemos que el coronavirus puede matar miles de personas sin saturarlas. (COVID-19 deaths are 20x more than traffic accidents, 100x more than homicides).

 

Álvarez P. Pandemia de desigualdad. El País 2020, published 2 October. Full-text: https://elpais.com/sociedad/2020-10-02/pandemia-de-desigualdad.html

La covid ahonda la brecha de género: las mujeres asumen más carga de trabajo y cuidados, son más frágiles ante la pobreza y la violencia y tienen menos voz en la toma de decisiones.

 

French

If you read French, read Roucaute D. Les restaurants sont-ils des lieux plus à risque pour la transmission du Covid-19 ? Le Monde 2020, published 2 October. Full-text : https://www.lemonde.fr/planete/article/2020/10/02/les-restaurants-sont-ils-des-lieux-plus-a-risque-pour-la-contamination-par-le-sars-cov-2_6054448_3244.html

Les études actuelles ne permettent pas d’affirmer le caractère superpropagateur de tous les restaurants, mais certains lieux favorisent des situations de transmission accrue du virus.