SARS-CoV-2 Infection Generates Long-Lived Memory B Cells Against the Receptor Binding Domain of the Spike Protein

In the current COVID-19 pandemic, understanding the establishment and longevity of SARS-CoV-2-specific circulating memory B cell (cMBC) response is essential for maintaining protective immunity. Thirty COVID-19 patients recruited during the outbreak in Singapore between January 2020 and April 2020 were analyzed for their cMBC response across multiple timepoints up to 12 months post-illness onset. Our data shows that RBD-specific cMBC numbers peak at 6 months to 12 months post-illness onset. cMBC establishment is delayed but more persistent with increasing disease severity. cMBC responses were not correlated in kinetics with plasma antibody responses, which peaked at 1 month post-illness onset and waned relatively rapidly. Levels of systemic IL-5 at 1 month and IL-7 at 6 months were associated with magnitude and persistence of RBD-specific cMBCs. These results demonstrate the relative longevity of the memory B cell response compared to plasma antibodies, highlighting their potential role in long-term protection against COVID-19.Funding: This work was supported by the Biomedical Research Council (BMRC), A*CRUSE (Vaccine monitoring project), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency for Science, Technology and Research (A*STAR), Singapore National Medical Research Council COVID-19 Research Fund (COVID19RF-001; COVID19RF-007; COVID19RF-0008; COVID19RF-060;) and A*STAR COVID-19 Research funding (H/20/04/g1/006). The SIgN Multiplex Analysis of Proteins (MAP) platform was supported by a grant from the National Research Foundation, Immunomonitoring Service Platform (ISP) (NRF2017_SISFP09).Declaration of Interests: A patent application for the SFB assay has been filed (Singapore patent #10202009679P: A Method Of Detecting Antibodies And Related Products) by Y.S.G, L.R., and L.F.P.N. The authors declare no other competing interests.Ethics Approval Statement: The study design and protocols for the COVID-19 PROTECT study group were evaluated by National Healthcare Group (NHG) Domain Specific Review Board (DSRB) and approved under study number 2012/00917. Collection of healthy donor samples was approved by SingHealth Centralized Institutional Review Board (CIRB) under study number 2017/2806 and NUS IRB 04-140. Written informed consent was obtained from participants in accordance with the Declaration of Helsinki for Human Research. The experiments conformed to the principles set out in the Department of Health and Human Services Belmont Report.