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Review 1: "Durable SARS-CoV-2 B cell immunity after mild or severe disease"

This study investigates B cell responses in COVID-19 patients and finds infection elicits S protein RBD-specific memory B cells in most participants. Reviewers deem the study reliable, but find some claims overreaching citing lack of functional data.

Published onJan 20, 2021
Review 1: "Durable SARS-CoV-2 B cell immunity after mild or severe disease"
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Durable SARS-CoV-2 B cell immunity after mild or severe disease
Description

AbstractMultiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-specific MBC in cohorts of ambulatory COVID-19 patients with mild disease, and hospitalized patients with moderate to severe disease, at a median of 54 (39-104) days after onset of symptoms. We detected S-RBD-specific class-switched MBC in 13 out of 14 participants, including 4 of the 5 participants with lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBC (rMBC) made up the largest proportion of S-RBD-specific class-switched MBC in both cohorts. FCRL5, a marker of functional memory when expressed on rMBC, was dramatically upregulated on S-RBD-specific rMBC. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched MBC that phenotypically resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after recovery from mild or severe COVID-19 disease.Graphical Abstract

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review:

The manuscript by Ogega et al. details the SARS-CoV-2 specific memory B cell response in response to mild and severe COVID-19 disease. It demonstrates that all but one study participant developed Spike receptor-binding domain (S-RBD) binding memory B cells. The most abundant subset of S-RBD binding cells consisted of resting memory B cells, including a portion that expressed FCRL5, a marker commonly found on functional memory B cells. The conclusions appear to be overreaching due to the lack of functional data associated with the memory B cells and the fact that it is a cross-sectional analysis that only examined 39-104 days post symptom onset.

Overall, the data is convincing and methodology appears to be sound and performed well from a technical standpoint. Results are largely consistent with studies published describing a robust induction of SARS-CoV-2 specific memory B cells and serum antibodies. The aspect of this manuscript that is most novel is the description of a significant population of FCRL5+ S-RBD-specific memory B cells. The expression of FCRL5 on memory B cells has previously been associated by other groups as contributing to an increased functional capacity. The enthusiasm about this data is slightly tempered by the lack of representative flow cytometry images demonstrating the gating strategy. The other limitation that this study faces is a limited sample size with only 7 study participants per group. Ultimately this manuscript would be improved upon by increasing the sample size, tracking study participants over time, and providing some direct evidence of increased functionality of S-RBD-specific FCRL5+ memory B cells. While this manuscript is well-written and technically sound, it does not ultimately support the claim of “Durable SARS-CoV-2 B cell immunity” as described in the title.

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