Top 10: October 27

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Bedford J, Enria D, Giesecke J, et al. Living with the COVID-19 pandemic: act now with the tools we have. Lancet 2020, published 24 October. Full-text:

Let’s face reality: at the beginning of the second pandemic wave, we have some steroids which have been shown to reduce mortality in patients with severe COVID-19 (see Corticosteroids); and then we have a drug (remdesivir, Veklury®), which had a marginal benefit in a company-sponsored trial. That’s the COVID-19 treatment armamentarium as of October 2020 (see COVID Reference: Treatment). David Heymann, Juliet Bedford and colleagues summarize how to get through the 2020/2021 winter with what we have.


Kambhampati AK, O’Halloran AC, Whitaker M, et al. COVID-19–Associated Hospitalizations Among Health Care Personnel — COVID-NET, 13 States, March 1–May 31, 2020. MMWR Morb Mortal Wkly Rep. ePub: 26 October 2020. DOI:

Healthcare personnel (HCP) can have severe COVID-19–associated illness. In this analysis of 13 sites representing 98 counties in 13 states (California, Colorado, Connecticut, Georgia, Maryland, Michigan, Minnesota, New Mexico, New York, Ohio, Oregon, Tennessee, and Utah), Anita Kambhampati et al. show that 6% of 6,760 adults hospitalized with COVID-19 during March 1–May 31, were HCP. Among HCP hospitalized with COVID-19, 36% were in nursing-related occupations, and 73% had obesity. Approximately 28% of these patients were admitted to an intensive care unit, 16% required invasive mechanical ventilation, and 4% died.



Plante JA, Liu Y, Liu J, et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature 2020, published 26. October. Full-text:

The spike protein mutation D614G has become dominant in the current SARS-CoV-2 pandemic. Now, Pei-Yong Shi, Jessica Plante and colleagues show that D614G enhances replication on human lung epithelial cells and primary human airway tissues through an improved infectivity of virions. The mutation might also enhance viral loads in the upper respiratory tract of COVID-19 patients and increase transmission. The authors suggest that therapeutic antibodies should be tested against the circulating G614 virus. Discover why the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19.



Denning D, Kilcoyne A, Ucer C, et al. Non-infectious status indicated by detectable IgG antibody to SARS-CoV-2. Br Dent J 229, 521–524 (2020). Full-text:

Dentists should know who is infectious and who is not. Here, David Denning and colleagues propose that those with a positive SARS-CoV-2 IgG antibody are non-infectious (>99% certainty) and that a positive SARS-CoV-2 IgG antibody is therefore a much more accurate determination of infectiousness than a repeat PCR which is only 70% sensitive. The big question for 2021: will SARS-Cov-2 vaccine responses include protective IgG titers?



Seow J, Graham C, Merrick B, et al. Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Nat Microbiol (2020). Full-text:

Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. But how long will antibody responses be maintained and will they provide protection from reinfection? To answer these questions, Katie Doores, Jeffrey Seow and colleagues collected sequential serum samples up to 94 d post onset of symptoms from 65 individuals with SARS-CoV-2 infection. They show that the kinetics of the neutralizing antibody response to SARS-CoV-2 is typical of an acute viral infection where a peak response is detected 3–4 weeks post-infection, which then wanes. Their results suggest that for individuals who develop a low neutralizing antibody response (ID50 100–300), titers can return to baseline over a relatively short period, whereas those who develop a robust neutralizing antibody response maintain titers >1,000 despite the initial decline. Must we already reconsider widespread serological testing and antibody protection against reinfection with SARS-CoV-2? The authors conclude that vaccine boosters might be required to provide long-lasting protection.



Daniloski Z, Jordan TX, Wessels HH, et al. Identification of required host factors for SARS-CoV-2 infection in human cells. Cell 2020, published 24 October. Full-text:

To identify potential therapeutic targets for SARS-CoV-2, Neville Sanjana, Zharko Daniloski and colleagues conduct a genome-wide CRISPR screen in human lung epithelial cells. They identify genes and pathways required for SARS-CoV-2 infection, including the vacuolar ATPase proton pump, Retromer, and Commander complexes. Using single-cell transcriptomics, they identify upregulation of cholesterol biosynthesis as a common mechanism underlying viral resistance, in addition to ACE2 sequestration.


Melin AD, Janiak MC, Marrone F, et al. Comparative ACE2 variation and primate COVID-19 risk. Commun Biol 3, 641 (2020). Full-text:

Some primate species develop COVID-19-like symptoms, but the susceptibility of most primates is unknown. Here, Amanda Melin et al. show that all apes and African and Asian monkeys (catarrhines) exhibit the same set of twelve key amino acid residues as human ACE2. Their results suggest that apes and African and Asian monkeys, and some lemurs, are likely to be highly susceptible to SARS-CoV-2. The authors call for urgent actions to limit the exposure of great apes to humans, and similar efforts may be necessary for many other primate species.



Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020 Oct;586(7830):516-527. PubMed: Full-text:

Brilliant review of SARS-CoV-2 vaccines: vaccine platforms, results from studies on non-human primates and results from phase 1/2 trials in humans. Read the review this evening and read it again next week.


Hensel J, McAndrews KM, McGrail DJ, et al. Protection against SARS-CoV-2 by BCG vaccination is not supported by epidemiological analyses. Sci Rep 10, 18377 (2020). Full-text:

Preliminary epidemiological analyses suggested that BCG vaccination might be associated with reduced COVID-19 cases and mortality. Might the BCG vaccine provide protection against infection with SARS CoV-2? (Seventeen clinical trials are currently registered to investigate the potential benefits of BCG vaccinations upon exposure to CoV-2.) Now, Raghu Kalluri, Janine Hensel and colleagues challenge this assumption. After correction for confounding variables, most notably testing rates, they found no association between BCG vaccination policy and COVD-19 spread rate or percent mortality.



Luo Y. Neanderthal DNA highlights complexity of COVID risk factors. Nature 2020, published 26 October. Full-text:

A genetic analysis reveals that some people who have severe reactions to the SARS-CoV-2 virus inherited certain sections of their DNA from Neanderthals. However, our ancestors can’t take all the blame for how someone responds to the virus. A comment on the paper we presented on October 2: Zeberg H, Pääbo S. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature September 30, 2020. Full-text: | 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.



Ledford H. The race to make COVID antibody therapies cheaper and more potent. Nature 2020, published 23 October. Full-text:

Injections of antibodies might prevent mild COVID-19 from becoming severe, but the treatments are expensive and difficult to make.



Art Copyright 2020: El País (reproduced with permission) | Zafra M, Salas J. Un salón, un bar y una clase: así contagia el coronavirus en el aire. El País 2020, published 25 October. Full-text:

Los interiores son más peligrosos, pero es posible minimizar los riesgos si se ponen en juego todas las medidas disponibles para combatir el contagio por aerosoles. Estas son las probabilidades de infección en estos tres escenarios cotidianos dependiendo de la ventilación, las mascarillas y la duración del encuentro.


Andrino B, Galocha A, Grasso D, Llaneras K. El factor K: por qué importa dónde nos infectamos. El País 2020, published, 27 October. Full-text:

Un 10% de contagios puede ser responsable del 80% de los casos. En España solo el 12% de los positivos se asocia a brotes conocidos.



If you read French, check  the following articles:

Cabut S, Santi P. Cancers, infarctus, AVC… la double peine des dégâts collatéraux du Covid-19. Le Monde 2020, published 26 October. Full-text:

Alors que la deuxième vague de la pandémie monte en France, les conséquences sanitaires de la désorganisation du système de santé lors du premier épisode, parfois mortelles, sont palpables. Tour d’horizon des pathologies aggravées par le coronavirus.


Dupont M. L’Etat au grand défi des épidémies. Le Monde 2020, published 23 October. Full-tex :

Depuis la peste d’Athènes au Ve siècle avant notre ère jusqu’au Covid-19 aujourd’hui, les crises sanitaires et épidémiques constituent un moment de vérité pour les institutions. Elles ont été souvent l’occasion d’un renforcement des structures étatiques.


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Bernd S. Kamps