Top 10: August 2

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By Christian Hoffmann &
Bernd S. Kamps

2 August

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<<< 006 | Summer Picture 007 / >>> 008 | Since 19 July, we have been preparing the Top 10 from a European beach location. While the friends enjoy the beach, we write the daily summaries.


Nguyen LH, Drew DA, Graham MS, et al. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. Lancet Public Health 2020, published 31 July. Full-text:

Front-line health care workers are at increased risk of SARS-CoV-2 infection. In a prospective, observational cohort study in the UK and the USA of the general community, including front-line health care workers, Andrew Chan and colleagues found that compared with the general community, front-line health care workers were at increased risk for reporting a positive COVID-19 test (adjusted HR 11·61, 95% CI 10·93–12·33). An increased risk (adjusted HR 3·40, 95% CI 3·37–3·43) was even found after accounting for differences in testing frequency between front-line health care workers and the general community. Post-hoc analyses showed that Black, Asian, and minority ethnic health care workers are at especially high risk of SARS-CoV-2 infection, with at least a fivefold (!) increased risk of COVID-19 compared with the non-Hispanic white general community.


de Souza WM, Buss LF, Candido DDS, et al. Epidemiological and clinical characteristics of the COVID-19 epidemic in Brazil. Nat Hum Behav. 2020 Jul 31. PubMed: Full-text:

Nuno Rodrigues Faria, Julio Croda and colleagues contextualize epidemiological, demographic and clinical findings for Brazilian COVID-19 cases in March, April and May 2020. By 31 May 2020, 514,200 COVID-19 cases and almost 30,000 deaths had been reported. They estimated a somewhat higher median transmission potential (R0) of SARS-CoV-2 of 3.1 (2.4–5.5) in Brazil compared with Italy, the United Kingdom, France, and Spain. As expected, more populated and better-connected municipalities were affected earlier, and less populated municipalities at a later stage of the epidemic.



Xiong X, Qu K, Ciazynska KA, et al. A thermostable, closed SARS-CoV-2 spike protein trimer. Nat Struct Mol Biol. 2020 Jul 31. PubMed: Full-text:

The spike (S) protein which mediates receptor binding and cell entry exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor-binding site and, subsequently, from pre-fusion to post-fusion conformations to mediate fusion of viral and cellular membranes. John Briggs, Xiaoli Xiong and colleagues now design mutations in the spike protein to allow the production of thermostable, disulfide-bonded S-protein trimers that are trapped in the closed, pre-fusion state. Furthermore, they demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. They anticipate a wide array of potential applications as a reagent for serology, virology and as an immunogen.



Gu H, Chen Q, Yang G, et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science 2020 Jul 30:eabc4730. PubMed: Full-text:

First, adapt a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. When the mouse-adapted strain shows increased infectivity in mouse lung after 6 passages, leading to interstitial pneumonia and inflammatory responses following intranasal inoculation, sequence the virus genome and look for adaptive mutations which might be associated with the increased virulence. That’s what Yusen Zhou, Cheng-Feng Qin, Shihui Sun, Shibo Jiang and colleagues did. They found an N501Y mutation located at the receptor binding domain (RBD) of the spike protein. They also showed the protective efficacy of a recombinant RBD vaccine candidate. They conclude that this MASCp6 could be of value in evaluating vaccines and antivirals against SARS-CoV-2.



Matheson NJ, Lehner PJ. How does SARS-CoV-2 cause COVID-19? Science 2020; 369:510-511. Full-text:

If you still have doubts about how SARS-CoV-2 enters human cells, read these two pages by Nicholas J. Matheson and Paul J. Lehner from Cambridge, UK. Find out what is so special about ACE2, what might cause the clinical deterioration that leads to severe systemic COVID-19 and how SARS-CoV-2 and our adaptive immune system, either antibodies or T cells, play together. The authors point out how essential it is to identify individuals with early SARS-CoV-2 infection who are at high risk of progression to severe disease. They recommend that treatment with future antiviral drugs should not be delayed until patients are hospitalized with severe lung injury.



Rugge M, Zorzi M, Guzzinati S. SARS-CoV-2 infection in the Italian Veneto region: adverse outcomes in patients with cancer. Nat Cancer 2020, published 31 July. Full-text:

Massimo Rugge, Manuel Zorzi and Stefano Guzzinati describe 9,275 patients with SARS-CoV-2 infection (CV2+ve), 723 of whom (7.8%) had a cancer diagnosis. The proportion of patients hospitalized was higher among patients with cancer (56.6% versus 34.4% among other patients), and so was the proportion of deaths (14.7% versus 4.5%). The risk of adverse outcomes of SARS-CoV-2 infection was significantly higher for patients with cancer versus those without, particularly for males and older people. Breast cancer and hematological cancers were associated with a higher risk of both hospitalization and death. Lung cancer was associated with a fourfold risk of death due to SARS-CoV-2 infection. The authors insist that the clinical importance of these results warrants further investigation.



Gellin B. Why vaccine rumours stick—and getting them unstuck. Lancet 2020, published 1 August. Full-text:

We will be living with the COVID-19 pandemic’s social and economic disruption until we are able to deploy effective vaccines globally. Unfortunately, vaccination policies have been and will be subject to political and ideological debate. Bruce Gellin presents Heidi Larson’s book How Vaccine Rumors Start—and Why They Don’t Go Away which looks at the vaccine debate through the lens of an anthropologist who has been studying vaccine confidence for decades.