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Zhao P, Praissman JL, Grant OC, et al. Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor. bioRxiv. 2020 Jul 24:2020.06.25.172403. PubMed: https://pubmed.gov/32743578. Full-text: https://doi.org/10.1101/2020.06.25.172403
A detailed understanding of SARS-CoV-2 Spike binding to ACE2 is critical for elucidating the mechanisms of viral binding and entry, as well as for the rational design of effective therapeutics. Here Lance Wells, Peng Zhao and colleagues utilize glycomics informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. The authors generate molecular dynamics simulations of each glycoprotein alone and interacting with one another. Their data and related similar findings might provide a framework to facilitate the production of immunogens, vaccines, antibodies, and inhibitors as well as providing additional information regarding mechanisms by which glycan microheterogeneity is achieved.
Ejemel M, Li Q, Hou S, et al. A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction. Nat Commun. 2020 Aug 21;11(1):4198. Full-text: https://doi.org/10.1038/s41467-020-18058-8
Pre- or post-exposure immunotherapies with neutralizing antibodies? Yang Wang, Monir Ejemel and colleagues describe a cross-reactive human IgA monoclonal antibody, termed MAb362, which binds to both SARS-CoV-1 and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 virus. The authors suggest that such SARS-CoV-2 specific IgA antibodies might provide immunity against SARS-CoV-2 by inducing mucosal immunity within the respiratory system, a potentially critical feature of an effective vaccine.
Lu S, Zhao Y, Yu W, et al. Comparison of nonhuman primates identified the suitable model for COVID-19. Sig Transduct Target Ther 5, 157 (2020). Full-text: https://doi.org/10.1038/s41392-020-00269-6
Within 6 months after SARS-CoV-2 was first reported, five kinds of animals were developed into models in which to study COVID-19: the mouse, ferret, tree shrew, golden hamster, and a nonhuman primate (NHP) species. Now Xiaozhong Peng, Shuaiyao Lu and colleagues characterized SARS-CoV-2 infection in three NHP models of COVID-19: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). M. mulatta most closely recapitulated human-like conditions, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues.
Johansen MD, Irving A, Montagutelli X, et al. Animal and translational models of SARS-CoV-2 infection and COVID-19. Mucosal Immunol. 2020 Aug 20:1-15. PubMed: https://pubmed.gov/32820248. Full-text: https://doi.org/10.1038/s41385-020-00340-z
Elucidating the mechanisms of pathogenesis will enable the identification of the most effective therapies. Head-to-head comparison of existing drugs, testing of safety, and the development of new and targeted preventions and treatments is most efficiently achieved using representative animal models of primary infection with validation of findings in primary human cells and tissues. Philip Hansbro, Matt Johansen and colleagues explore and discuss the diverse animal, cell and tissue models that are being used and developed. A 10-page read with 246 references for your next weekend.
Feng L, Wang Q, Shan C, et al. An adenovirus-vectored COVID-19 vaccine confers protection from SARS-COV-2 challenge in rhesus macaques. Nat Commun 11, 4207 (2020). Full-text: https://doi.org/10.1038/s41467-020-18077-5
Ling Chen, Liqiang Feng and colleagues report the generation of a replication-incompetent recombinant serotype 5 adenovirus, Ad5-S-nb2, which elicited systemic S-specific antibody and cell-mediated immune (CMI) responses in mice and rhesus macaques both after intramuscular injection and intranasal inoculation. At 30 days after a single vaccination with Ad5-S-nb2, macaques were protected against SARS-CoV-2 challenge.
McCarty TR, Hathorn KE, Redd WD, et al. How Do Presenting Symptoms and Outcomes Differ by Race/Ethnicity Among Hospitalized Patients with COVID-19 Infection? Experience in Massachusetts. Clin Infect Dis 2020, published 22 August. Full-text: https://doi.org/10.1093/cid/ciaa1245
Pre-existing societal inequities, many of which are a result of long-standing structural racism, place Black and Latinx communities and individuals at greater risk of being adversely affected by such disasters. But is there an association between race/ethnicity and clinically relevant hospitalization outcomes, including in-hospital mortality? Walter Chan, Thomas McCarthy and colleagues invite to a differentiated appraisal in this retrospective analysis of nine Massachusetts hospitals including all consecutive adult patients hospitalized with laboratory-confirmed COVID-19 (n=379). Latinx patients were younger, had fewer cardiopulmonary disorders, were more likely to have obesity, more frequently reported fever and myalgia, and had lower D-dimer levels compared to White patients (p<0.05). However, after controlling for confounders (age, gender, obesity, cardiopulmonary comorbidities, hypertension, and diabetes), no significant differences in in-hospital mortality, ICU admission, or mechanical ventilation by race/ethnicity were found. In other words: despite a disproportionate infection rate among Black and Latinx individuals, when their disease is severe enough to require hospitalization, these patients do just as well in terms of important outcomes, including mortality.
Stefanini GG, Chiarito M, Ferrante G, et al. Early detection of elevated cardiac biomarkers to optimise risk stratification in patients with COVID-19. Heart. 2020 Aug 14:heartjnl-2020-317322. PubMed: https://pubmed.gov/32817312. Full-text: https://doi.org/10.1136/heartjnl-2020-317322
An early risk stratification is crucial in order to identify the patients that might benefit from intense monitoring and aggressive treatment strategies. Here Giulio Stefanini et al. stratify 397 patients according to elevated levels of high-sensitivity cardiac troponin I (hs-TnI, a biomarker of myocardial injury), B-type natriuretic peptide (BNP, a biomarker of cardiac stress) or both measured within 24 hours after hospital admission. The rate of mortality was higher in patients with elevated hs-TnI (22.5%), BNP (33.9%) or both (55.6%) as compared with those without elevated cardiac biomarkers (6.25%). The authors recommend cardiac biomarkers to be systematically assessed in patients with COVID-19 at the time of hospital admission.
Matsuzawa Y, Ogawa H, Kimura K, et al. Renin-angiotensin system inhibitors and the severity of coronavirus disease 2019 in Kanagawa, Japan: a retrospective cohort study. Hypertens Res. 2020 Aug 21. PubMed: https://pubmed.gov/32820236. Full-text: https://doi.org/10.1038/s41440-020-00535-8
Again: does the preceding use of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) ACEIs and ARBs affect the clinical manifestations and prognosis of COVID-19 patients? Yasushi Matsuzawa et al. analyzed 151 consecutive patients (mean age 60 ± 19 years) with SARS-CoV-2 infection in a retrospective observational study. Age ≥ 65 years was significantly associated (odds ratio 6.63) with the primary composite outcome (1. in-hospital death, 2. extracorporeal membrane oxygenation, 3. mechanical ventilation, including invasive and noninvasive methods, and 4. admission to the intensive care unit). In COVID-19 patients with hypertension, preceding ACEI/ARB use was significantly associated with a lower occurrence of new-onset or worsening mental confusion (OR 0.06). The authors conclude that ACEIs/ARBs could be beneficial for the prevention of confusion in COVID-19 patients with hypertension.
Lane JCE, Weaver J, Kostka K. Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study. Lancet Rheumatol 2020, published 21 August. Full-text: https://doi.org/10.1016/S2665-9913(20)30276-9
Hydroxychloroquine (HCl) is like some presidents: it is useless and people should stop talking about it. As a matter of fact, we stopped reporting on the HCl soup opera weeks ago. If, nonetheless, you cannot resist watching the episodes, here you go: when combined with azithromycin, as sung by a French bard, hydroxychloroquine increases the risk of heart failure and cardiovascular mortality.
If you read French, read Santi P, Hecketsweiler C. Coronavirus : pourquoi le port obligatoire du masque se généralise en France ; Le Monde 2020, published 22 August. Full-text : https://www.lemonde.fr/planete/article/2020/08/22/de-nice-a-lille-la-france-se-convertit-au-port-du-masque_6049607_3244.html
Wearing face masks outdoors is now fully or partially imposed in around 12,300 (one third of all) municipalities, and will be in businesses, colleges and high schools from September 1. Pascale Santi and Chloé Hecketsweiler analyze the history of face mask acceptation.