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Yao H, Song Y, Chen Y, et al. Molecular architecture of the SARS-CoV-2 virus. Cell 2020, published 14 September. Full-text: https://doi.org/10.1016/j.cell.2020.09.018
How does a virus pack its ∼30 kb long single-segmented RNA in a ∼80 nm diameter lumen? Here, Sai Li, Lanjuan Li and Hangping Yao report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography and subtomogram averaging. From ~2,300 intact virions, the authors provide molecular insights into the structures of spikes in the pre- and postfusion conformations, the RNPs and how they assemble on the authentic virus. They also analyzed the detailed glycan compositions of the native spikes.
Yurkovetskiy L, Wang X, Pascal KE, et al. Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant. Cell 2020, published 15 September. Full-text: https://doi.org/10.1016/j.cell.2020.09.032
The SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide in a matter of months, suggesting that the mutation confers a replication advantage. Here, the authors show that D614G is more infectious than the ancestral form on human lung cells, colon cells, and on cells rendered permissive by ectopic expression of human, while not alterating S protein synthesis, processing, or incorporation into SARS-CoV-2 particles. Remember that the D614G variant is not associated with more severe COVID-19.
Rydyznski Moderbacher C, Ramirez SI, Dan JM, et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell 2020, published 16 September. Full-text: https://doi.org/10.1016/j.cell.2020.09.038
Age is a disturbing risk factor in SARS-CoV-2 infection. Here, Shane Crotty, Alessandro Sette, Carolyn Rydyznski Moderbacher and colleagues present a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses. They confirm that the coordination of SARS-CoV-2 antigen-specific responses is disrupted in individuals > 65 years old. Scarcity of naive T cells was also associated with ageing and poor disease outcomes.
Piccoli L, Park YJ, Tortorici MA, et al. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Cell 2020, published 16 September. Full-text: https://doi.org/10.1016/j.cell.2020.09.037
David Veesler, Luca Piccoli and colleagues provide an extensive analysis of Ab responses to SARS-CoV-2 S, 526 RBD and N in more than 600 SARS-CoV-2 infected individuals with different clinical outcomes. They found that the SARS-CoV-2 receptor-binding domain (RBD) is immunodominant, accounting for 90% of serum neutralizing activity and that RBD antibodies decline with a half-life of ∼50 days. They also identified two major receptor-binding motif antigenic sites. The authors are confident that their results “will guide the design of COVID-19 vaccines and therapeutics”.
Sun Y, Kobe B, Qi J. Targeting multiple epitopes on the spike protein: a new hope for COVID-19 antibody therapy. Sig Transduct Target Ther 5, 208 (2020). https://doi.org/10.1038/s41392-020-00320-6
Do you remember our July 23 entry for Liu L, Wang P, Nair MS, et al. [Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike. Nature 2020, published 22 July. Full-text: https://doi.org/10.1038/s41586-020-2571-7]? Find now a detailed description of the paper. The authors conclude that the variety of potent neutralizing monoclonal antibodies against SARS-CoV-2 “inspires optimism that we will be able to find highly effective and safe candidates for clinical treatment of the COVID-19”. Effective mAb cocktail treatments on the horizon?
Khanh NC, Thai PQ, Quach H-L, Thi NA-H, Dinh PC, Duong TN, et al. Transmission of severe acute respiratory syndrome coronavirus 2 during long flight. Emerg Infect Dis 2020, published 18 September. Full-text: https://doi.org/10.3201/eid2611.203299
The authors report a cluster of cases among passengers on VN54 (Vietnam Airlines), a 10-hour commercial flight from London to Hanoi on March 2, 2020. Among the 16 persons in whom SARS-CoV-2 infection was detected, 12 (75%) were passengers seated in business class along with the only symptomatic person (attack rate 62%). The authors find that blocking middle seats, currently recommended by the airline industry, may in theory prevent some in-flight transmission events but seems to be insufficient to prevent superspreading events. They conclude that the risk for on-board transmission of SARS-CoV-2 during long flights is real and has the potential to cause COVID-19 clusters of substantial size, even in business class–like settings with spacious seating arrangements well beyond the established distance used to define close contact on airplanes.
(Note that at the time, March 2, the use of face masks was not mandatory on airplanes or at airports, and there was no social distancing on the aircraft.)
Figure 1. Seating location of passengers on Vietnam Airlines flight 54 from London, UK, to Hanoi, Vietnam, on March 2, 2020, for whom severe acute respiratory syndrome coronavirus 2 infection was later confirmed. Copyright 2020: CDC. Reproduced with permission.
Westblade LF, Brar G, Pinheiro LC, et al. SARS-CoV-2. Viral Load Predicts Mortality in Patients with and Without Cancer Who Are Hospitalized with COVID-19. Cancer Cell 2020, published 15 September. Full-text: https://doi.org/10.1016/j.ccell.2020.09.007.
The predictive value of viral load? The authors measured SARS-CoV-2 viral load in nasopharyngeal swab specimens of 100 patients with cancer and 2914 without cancer who were admitted to three New York City hospitals. Overall, the in-hospital mortality rate was 38.8% among patients with a high viral load, 24.1% among patients with a medium viral load, and 15.3% among patients with a low viral load (P<0.001). Similar findings were observed in patients with cancer. The authors also found that patients with hematologic malignancies had higher median viral loads than patients without cancer. They conclude that viral load measurements might be a valuable tool for clinicians in the care of hospitalized patients with COVID-19.
White-Dzuro G, Gibson LE, Zazzeron L, et al. Multisystem effects of COVID-19: A concise review for practitioners. Postgrad Med. 2020 Sep 14. PubMed: https://pubmed.gov/32921198. Full-text: https://doi.org/10.1080/00325481.2020.1823094
The authors review the multisystem complications of COVID-19 and treatment strategies to improve the care of critically ill COVID-19 patients. They stress that clinicians should be aware of the multisystem impact of the disease so that care can be focused on the prevention of end-organ injuries to potentially improve clinical outcomes.
Zhou Y, Shi H, Liu Z, et al. The prevalence of psychiatric symptoms of pregnant and non-pregnant women during the COVID-19 epidemic. Transl Psychiatry 10, 319 (2020). https://doi.org/10.1038/s41398-020-01006-x
Should pregnancy shield women from depression and anxiety in these COVID times? The authors enrolled 544 pregnant women and 315 non-pregnant women. In this study, 5.3%, 6.8%, 2.4%, 2.6%, and 0.9% of pregnant women were identified to have symptoms of depression, anxiety, physical discomfort, insomnia, and post-traumatic stress disorder (PTSD), respectively. However, the corresponding prevalence rates among non-pregnant women were 17.5%, 17.5%, 2.5%, 5.4%, 5.7%, respectively. In China, pregnant women seemed to have an advantage of facing mental problems caused by COVID-19.
Adebisi YA, Alaran AJ, Akinokun RT, Micheal AI, Ilesanmi EB, Lucero-Prisno DE. Sex Workers Should not Be Forgotten in Africa’s COVID-19 Response. Am J Trop Med Hyg. 2020 Sep 15. PubMed: https://pubmed.gov/32940202. Full-text: https://doi.org/10.4269/ajtmh.20-1045
Sex workers in Africa are among one of the vulnerable populations, face high levels of stigma and discrimination (why not their clients?), are excluded from African government safety net and cannot observe physical distancing and other precautionary measures. A two-page perspective.
If you read French, read Entre mort et vie, la zone grise du Covid-19. Le Monde 2020, published 19 September. Full-text: https://www.lemonde.fr/idees/article/2020/09/19/entre-mort-et-vie-la-zone-grise-du-covid-19_6052842_3232.html
Alors que les bilans et les projections s’attachent à dénombrer cas, hospitalisations et décès, ils laissent dans l’ombre une dimension majeure de la maladie : ses formes longues et les séquelles associées.