Functional SARS-CoV-2-specific immune memory persists after mild COVID-19
cell biology immunology/immunity
Authors:Rodda et al.,
Journal/ Pre-Print:Researchsquare
Tags: Immunology/Immunity, Cell Biology
Research Highlights
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Mild COVID-19 infection induces persistent, neutralising anti-SARS-CoV-2 IgG antibody and a sustained enrichment of RBD-specific memory B cells.
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Mild COVID-19-induced SARS-CoV-2-specific memory B cells which can express functional and neutralising antibodies.
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SARS‑CoV‑2 infection induces durable, functional spike-reactive CD4+ and CD8+ T cells persisted over three months after infection.
Summary
Accumulating evidence highlights the role of B and T cell responses to SARS-CoV-2 infection but the durability of the responses is still unknown. In this elegant study, the authors performed a longitudinal analysis of 15 individuals recovered from mildly symptomatic COVID-19 to investigate the persistence of virus specific memory T and B cell responses a month or 3 months post symptom onset. These patients were compared to healthy controls (contemporaneously and pre-pandemic). Individuals who recovered from symptomatic COVID-19 developed persisting antibody responses with neutralisation activity which was maintain over three months after SARS-CoV2 infection. Interestingly, SARS-CoV-2-specific memory B cells (MBCs) were not only persisted but increased in number in some cases over 3 months with prominent population of RBD-specific IgG+CD27+CD21+T-betlo MBCs. These MBCs expressed BCRs capable of neutralizing the virus by producing functional neutralizing antibody responses upon re-stimulation with antigen. In addition to B cells, SARS-CoV-2-specific memory CD4 T cells persisted over three months, expressing Th-1 and Th-17 associated cytokine profiles with proliferative capacity upon antigen stimulation, suggesting a durable and functional T cell responses. Over this time period, S-specific memory CD8+ T cells also developed. Collectively, these data suggest that mild COVID-19 infection can result in memory responses which persist and display functional hallmarks associated with antiviral protective immunity.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19
Understand the virology and/or cell biology of SARS-CoV2/COVID19
Study Type
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In vitro study
Strengths and limitations of the paper
Novelty: The study provides an insight to protective immunity and the durability of memory adaptive responses in mild COVID-19 infection.
Standing in the field: SARS-Cov-2 infection has been reported to induce transient antibody responses (although in some cases still detectable responses) (Jeffrey Seow,et al, 2020).
Appropriate statistics: Yes
Viral model used:SARS-CoV-2
Translatability: The study suggests that mild infection can induce protective response to re-exposure that could contribute to herd immunity and curtailing this pandemic, and may be relevant to vaccination strategies
Main limitations:
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The study performs the analysis of memory responses at two time points (1 month and 3 months after symptom onset). However it is not clear how these compare with the acute phase of the infection. This may be important given that antibody responses could peak and decline in the 3 weeks after infection (Long et al, Nature, 2020)
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As the authors discussed, the contribution of the cross-reactive CD4 T cells found in their control groups to the expanded SARS-CoV-2-specific cells and their protective capacity was not assessed.
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While the authors discussed the contribution of CD4+ cTfh to help and maintain germinal center responses, minimal evidence was reprorted for the IL-21 responses of Tfh cells, given its major role in germinal center B cell differentiation and proliferation (Dimitra Zotos et al, J Exp Med, 2010).
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It would be interesting to understand whether T cells that proliferate/activate in response to virus are able to kill infected cells, although this is recognised as an experimental challenge.