Long-lived bone marrow plasma cells (BMPCs) are a persistent and essential source of protective antibodies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent individuals have a significantly lower risk of reinfection. Nonetheless, it has been reported that anti-SARS-CoV-2 serum antibodies experience rapid decay in the first few months after infection, raising concerns that long-lived BMPCs may not be generated and humoral immunity against this virus may be short-lived. Here we demonstrate that in patients who experienced mild infections (n=77), serum anti-SARS-CoV-2 spike (S) antibodies decline rapidly in the first 4 months after infection and then more gradually over the following 7 months, remaining detectable at least 11 months after infection. Anti-S antibody titers correlated with the frequency of S-specific BMPCs obtained from bone marrow aspirates of 18 SARS-CoV-2 convalescent patients 7 to 8 months after infection. S-specific BMPCs were not detected in aspirates from 11 healthy subjects with no history of SARS-CoV-2 infection. We demonstrate that S-binding BMPCs are quiescent, indicating that they are part of a long-lived compartment. Consistently, circulating resting memory B cells directed against the S protein were detected in the convalescent individuals. Overall, we show that SARS-CoV-2 infection induces a robust antigen-specific, long-lived humoral immune response in humans.
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