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By Christian Hoffmann &
Bernd S. Kamps
19 August
Virology
Ke Z, Oton J, Qu K, et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nature 2020, published 17 August. Full-text: https://doi.org/10.1038/s41586-020-2665-2
Fully understanding how SARS-CoV-2 Spike (S) proteins function and how they interact with the immune system, requires knowledge of the structures, conformations and distributions of S trimers within virions. Now John Briggs and colleagues collect viral particles from infected cells and determine the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. They express optimism that cryo-electron microscopy can be used to study antibody binding to S in the context of the viral surface. Such studies would provide insights into how neutralizing antibodies block virus infection, particularly for antibodies against membrane-proximal regions of S, and could thus inform design of immunogens for vaccination.
Turoňová B, Sikora M, Schürmann C, et al. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges. Science 2020, published 18 August. Full-text: https://science.sciencemag.org/content/early/2020/08/17/science.abd5223
If you are not a virologist, cryo electron tomography, sub-tomogram averaging and molecular dynamics simulations may all be Greek to you. To structurally analyze the SARS-CoV-2 Spike (S) protein in situ, Martin Beck, Jacomina Locker, Gerhard Hummer and colleagues did exactly that. They show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom, and propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat.
Model of the S protein. The three individual chains of S are shown in shades of red, N-glycosylation in blue, lipids of the ER-like membrane in gray with phosphates in green; “hip,” “knee” and “ankle” mark positions of the three flexible hinges. Reproduced with permission.
Transmission
Asadi S, Gaaloul ben Hnia N, Barre RS, et al. Influenza A virus is transmissible via aerosolized fomites. Nat Commun 11, 4062 (2020). Full-text: https://doi.org/10.1038/s41467-020-17888-w
SARS-CoV-2 can be transmitted via droplets, fomites and possibly aerosol. Will we need to get accustomed to a fourth transmission route, aerosolized fomites? That’s what Nicole Bouvier and colleagues suggest, although for now only for influenza A virus. They show that dried influenza virus remains viable in the environment, on materials like paper tissues and on the bodies of living animals, long enough to be aerosolized on non-respiratory dust particles that can transmit infection through the air to new mammalian hosts. Will we soon see a paper about SARS-CoV-2 transmission via aerosolized fomites?
Schematic for aerodynamic particle sizer (APS) experiments to quantify the airborne particulates generated by awake, unrestrained (mobile) guinea pigs. Reproduced with permission.
Prevention
Grassly NC, Pons-Salort M, Parker EPK, et al. Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study. Lancet Infect Dis 2020, published 18 August. Full-text: https://doi.org/10.1016/S1473-3099(20)30630-7
Tedros Adhanom Ghebreyesus didn’t get everything right in the SARS-CoV-2 pandemic, but he was right when he recommended: “Test, test, test!” (WHO, 16 March 2020; see also our Prevention chapter), but countries have taken different approaches and the effectiveness of alternative strategies is unknown. Now Nicolas Grassly and colleagues from the Imperial College COVID-19 Response Team investigate the potential impact of different testing and isolation strategies on SARS-CoV-2 transmission. Their conclusion: “Molecular testing can play an important role in prevention of SARS-CoV-2 transmission, especially among health-care workers and other high-risk groups, but no single strategy will reduce R below 1 at current levels of population immunity. Immunity passports based on antibody tests or tests for infection face substantial technical, legal, and ethical challenges.
Immunology
Young BE, Fong SW Chan YH, et al. Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. Lancet 2020, published 18 August. Full-text: https://doi.org/10.1016/S0140-6736(20)31757-8
In January and February 2020, a SARS-CoV-2 variant with a 382-nucleotide deletion (Δ382) in the open reading frame 8 was detected in a cluster of cases in Singapore. Now Lisa Ng, Gavin Smith and colleagues compared the clinical outcomes and immune responses of patients infected with wild type and Δ382 SARS-CoV-2. Of 131 patients enrolled onto the study, 92 (70%) were infected with the wild type virus, ten (8%) had a mix of wild type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Their finding: development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 of 29 patients) than in the wild type only group (26 [28%] of 92). They conclude that “further study of these variants could improve our understanding of SARS-CoV-2 virology and pathogenesis and could have implications for the development of treatments and vaccines.”
Clinical
Iadecola C, Anrather J, Kamel H. Effects of COVID-19 on the nervous system. Cell 2020, published 19 August. Full-text: https://www.cell.com/cell/fulltext/S0092-8674(20)31070-9
Many hospitalized COVID-19 patients exhibit neurological manifestations, ranging from headache and loss of smell, to confusion and disabling strokes. The disease might also take a toll on the nervous system in the long term. Follow Costantino Iadecola, Josef Anrather and Hooman Kamel in this appraisal of the potential for neurotropism and mechanisms of neuropathogenesis of SARS-CoV-2.
Comorbidities
Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol 2020;19:767-83. PubMed: https://pubmed.gov/32622375. Full-text: https://doi.org/10.1016/S1474-4422(20)30221-0
Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic may prove challenging, especially if primary COVID-19 illness occurred weeks earlier. Tom Solomon and colleagues navigate you through the neurological complications of COVID-19 in this ‘Rapid (15 pages) Review”.
Fifi JT, Mocco J. COVID-19 related stroke in young individuals. Lancet Neurol 2020;19:713-715. Full-text: https://doi.org/10.1016/S1474-4422(20)30272-6
SARS-CoV-2 infection may cause thrombotic vascular events. In patients presenting with large vessel stroke during the COVID-19 pandemic, COVID-19 patients were significantly younger, with a mean age of 59 years, than patients who tested negative for SARS-CoV-2, who had a mean age of 74 years. Johanna Fifi and J Mocco recommend that, in otherwise healthy, young patients who present with stroke during the pandemic, the diagnosis of COVID-19 should be thoroughly investigated.
Journal Feature
Editorial. Progress report on the coronavirus pandemic. Nature 2020, published 19 August. Full-text: https://www.nature.com/articles/d41586-020-02414-1
In the first of a series of editorials, Nature looks back at some of the key findings from the scientists race to demystify SARS-CoV-2: cracking the virus code, comorbidities, modes of infection, aerosols and asymptomatic infection.
McKenna M. The antibiotic paradox: why companies can’t afford to create life-saving drugs. Nature 2020, published 19 August. Full-text: https://www.nature.com/articles/d41586-020-02418-x
The antibiotic market seems to be broken. For almost two decades, the large corporations that once dominated antibiotic discovery have been fleeing the business. It takes around 20 years to see any profit from a newly developed antibiotic and prices the companies can charge for antibiotics are too low to support the cost of developing them. Join Maryn McKenna while she discovers omadacycline (trade name: Nuzyra) which went on sale in the US in 2019 for use against bacterial infections.