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Levy Library Blog

Article in the Spotlight: July 2021

by Angelyn Thornton on 2021-07-28T08:00:00-04:00 | Comments

 

Each month Levy Library showcases the achievements of Mount Sinai faculty and researchers by highlighting an article and its altmetrics. Altmetrics are alternative measures of impact that capture non-traditional data like abstract views, article downloads, and social media activity. Our altmetrics data is provided by the PlumX platform

 

This month we highlight Evolution of antibody immunity to SARS-CoV-2. This article was written in part by Saurabh Mehandru, MD.

 

 

Citation Data

Nature, ISSN: 1476-4687, Vol: 591, Issue: 7851, Page: 639-644

 

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

 

ad, Results of ELISAs measuring plasma reactivity to RBD (abc) and N protein (d) at the initial 1.3- and 6.2-month follow-up visit, respectively. a, Anti-RBD IgM. b, Anti-RBD IgG. c, Anti-RBD IgA d, Anti-N IgG. The normalized area under the curve (AUC) values for 87 individuals are shown in ad for both time points. Positive and negative controls were included for validation1e, Relative change in plasma antibody levels between 1.3 and 6.2 months for anti-RBD IgM, IgG, IgA and anti-N IgG in all 87 individuals. fi, Relative change in antibody levels between 1.3 and 6.2 months plotted against the corresponding antibody levels at 1.3 months. f, Anti-RBD IgM. r = −0.83, P < 0.0001. g, Anti-RBD IgG. r = −0.76, P < 0.0001. h, Anti-RBD IgA. r = −0.67, P < 0.0001. i, Anti-N IgG. r = −0.87, P < 0.0001. j, Ranked average NT50 at 1.3 months (blue) and 6.2 months (red) for the 87 individuals studied. k, Graph shows NT50 for plasma from all 87 individuals collected at 1.3 and 6.2 months. P < 0.0001. l, Relative change in plasma neutralizing titres between 1.3 and 6.2 months plotted against the corresponding titres at 1.3 months. For aek plotted values and horizontal bars indicate geometric mean. Statistical significance was determined using two-tailed Wilcoxon matched-pairs signed-rank test in adk, and Friedman with Dunn’s multiple comparison test in e. The r and P values in fil were determined by two-tailed Spearman’s correlations.
Image via Nature

 

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