Top 10: September 18

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By Christian Hoffmann &
Bernd S. Kamps

18 September

Virology

Benton DJ, Wrobel AG, Xu P, et al. Receptor binding and priming of the spike protein of SARS-CoV-2 for membrane fusion. Nature (2020). https://doi.org/10.1038/s41586-020-2772-0

After investigating the binding of ACE2 to the furin-cleaved form of SARS-CoV-2 S by cryoEM, Steven Gamblin, Donald Benton and colleagues propose mechanistic suggestions for the early stages of SARS-CoV-2 infection of cells. The authors classified ten different molecular species including the unbound, closed spike trimer, the fully open ACE2-bound trimer, and dissociated monomeric S1 bound to ACE2.

 

Transmission

Meyerowitz EA, Richterman A, Gandhi RT, Sax PE. Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors. Ann Intern Med 2020, published 17 September. Full-text: https://doi.org/10.7326/M20-5008

Eric Meyerowitz et al. present a comprehensive review of the evidence of human SARS-CoV-2 transmission. Their key points:

  1. Respiratory transmission is the dominant mode of transmission.
  2. Vertical transmission occurs rarely; transplacental transmission has been documented.
  3. Cats and ferrets can be infected and transmit to each other, but there are no reported cases to date of transmission to humans; minks transmit to each other and to humans.
  4. Direct contact and fomite transmission are presumed but are likely only an unusual mode of transmission.
  5. Although live virus has been isolated from saliva and stool and viral RNA has been isolated from semen and blood donations, there are no reported cases of SARS-CoV-2 transmission via fecal–oral, sexual, or bloodborne routes. To date, there is 1 cluster of possible fecal–respiratory transmission.

 

Prevention

Zeng W, Wang X, Li J, et al. Association of Daily Wear of Eyeglasses With Susceptibility to Coronavirus Disease 2019 Infection. JAMA Ophthalmol. Published online September 16, 2020. Full-text: https://doi.org/10.1001/jamaophthalmol.2020.3906

Yiping Wei, Weibiao Zeng and colleagues describe 276 patients from Hubei Province, China, at the beginning of the pandemic. They found that the proportion of the patients who reported routinely wearing eyeglasses more than 8 hours per day (5.8%; 16 of 276 patients) was lower than in the general population (31.5%). The authors suggest that daily wearers of eyeglasses may be less susceptible to COVID-19. See also the comment by Maragakis LL. Eye Protection and the Risk of Coronavirus Disease 2019: Does Wearing Eye Protection Mitigate Risk in Public, Non–Health Care Settings? JAMA Ophthalmol 2020, published 16 September. Full-text: https://doi.org/10.1001/jamaophthalmol.2020.3909

 

Immunology

Jones D, Helmreich S. A history of herd immunity. Lancet 2020, published 19 September. Full-text: https://doi.org/10.1016/S0140-6736(20)31924-3

Do you remember the discussion about herd immunity in March 2020? And one of those who imprudently endorsed the notion who ended up needing intensive care? David Jones and Stefan Helmreich point out that “The language of herd immunity is part of the problem. A herd usually describes domesticated animals, especially livestock. Herd animals like cows, goats, or sheep are sacrificed for human consumption. Few humans want to be part of that kind of herd.” Follow them on voyage through history.

 

Huang M, Lu Q, Zhao H, et al. Temporal antibody responses to SARS-CoV-2 in patients of coronavirus disease 2019. Cell Discov 6, 64 (2020). https://doi.org/10.1038/s41421-020-00209-2

Wuxiang Guan, Min Huang and colleagues assessed the longitudinal clinical, laboratory, viral, and immunological data from 366 COVID patients. SARS-CoV-2-specific IgM and IgG antibody titer reached the peak levels at 3–4 weeks. The authors predict IgM to last for about two months while IgG titer might diminish 7 months after symptom onset. Patients with older age or severe disease achieved a higher IgG level than patients of younger age and mild disease.

 

Xi Y. Convalescent plasma therapy for COVID-19: a tried-and-true old strategy? Sig Transduct Target Ther 5, 203 (2020). https://doi.org/10.1038/s41392-020-00310-8

Yongzhi Xi discusses the benefits and challenges of convalescent plasma therapy. One major challenge is the antibody-dependent enhancement (ADE) of viral infection mediated by pre-existing enhancing, non-neutralizing, or sub-neutralizing levels of antibodies from the convalescent plasma administered.

 

Grant OC, Montgomery D, Ito K, Woods RJ. Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition. Sci Rep 10, 14991 (2020). https://doi.org/10.1038/s41598-020-71748-7

Robert Woods, Oliver Grant and colleagues elucidate the role of glycans which might shield from antibody recognition up to 40% of the underlying protein surface of the S glycoprotein trimer. Could glycans alter the innate or adaptive immune response? And, given that glycan microheterogeneity varies between individuals, and depends on many factors, including age, underlying disease and ethnicity, is this a molecular basis for the observed differential susceptibilities among individuals to SARS-CoV-2 infection?

 

Diagnostics

Gibani MM, Toumazou C, Sohbati M, et al. Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge): a diagnostic accuracy study. Lancet Microbe 2020, published 17 September. Full-text: https://doi.org/10.1016/S2666-5247(20)30121-X

Access to rapid diagnosis is key to the control of the SARS-CoV-2 pandemic. In the future, point-of-care testing could relieve pressure on centralized laboratories and increase overall testing capacity. Here, Graham Cooke, Malick Gibani and colleagues describe a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. Their CovidNudge test 2 had 94% sensitivity and 100% specificity when compared with standard laboratory-based RT-PCR.

 

Treatment

Liu STH, Lin H, Baine I, et al. Convalescent plasma treatment of severe COVID-19: a propensity score–matched control study. Nat Med (2020). https://doi.org/10.1038/s41591-020-1088-9

Retrospective, propensity score–matched case–control study assessment in 39 patients. Patients who received convalescent plasma required somewhat less oxygen; preliminary data might suggest a mortality benefit. The authors conclude that greater numbers and a randomized trial are needed to draw definitive conclusions about the efficacy of convalescent plasma for the treatment of COVID-19.

 




Spanish

If you read Spanish, read Valdés I. El 64% de las UCI de Madrid ya están ocupadas por enfermos de covid. El País 2020, published 18 September. Full-text: https://elpais.com/sociedad/2020-09-17/el-64-de-las-uci-de-madrid-ya-estan-ocupadas-por-enfermos-de-covid.html

La capacidad original de intensivos de la región es de 641 camas… Este jueves, ya había 409 pacientes graves ocupando esas camas: el 63,8%.