SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans.

Jackson S Turner,Jane A O’Halloran,Aaron J Schmitz,Charles W Goss,Elizaveta Kalaidina,Rachel M Presti,Iskra Pusic,Ali H Ellebedy,Lena Hansen,Michael K Klebert,Adriana M Rauseo,Alem Haile,Wooseob Kim

doi:10.1038/s41586-021-03647-4

Jackson S Turner, Jane A O’Halloran + Show 11 more

Open Access

https://doi.org/10.1038/s41586-021-03647-4

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Abstract

Long-lived bone marrow plasma cells (BMPCs) are a persistent and essential source of protective antibodies1-7. Individuals who have recovered from COVID-19 have a substantially lower risk of reinfection with SARS-CoV-28-10. Nonetheless, it has been reported that levels of anti-SARS-CoV-2 serum antibodies decrease rapidly in the first few months after infection, raising concerns that long-lived BMPCs may not be generated and humoral immunity against SARS-CoV-2 may be short-lived11-13. Here we show that in convalescent individuals who had experienced mild SARS-CoV-2 infections (n=77), levels of serum anti-SARS-CoV-2 spike protein (S) antibodies declined 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 titres correlated with the frequency of S-specific plasma cells in bone marrow aspirates from 18 individuals who had recovered from COVID-19 at 7 to 8 months after infection. S-specific BMPCs were not detected in aspirates from 11 healthy individuals with no history of SARS-CoV-2 infection. We show that S-binding BMPCs are quiescent, which suggests that they are part of a stable compartment. Consistently, circulating resting memory Bcells directed against SARS-CoV-2 S were detected in the convalescent individuals. Overall, our results indicate thatmild infection with SARS-CoV-2 induces robust antigen-specific, long-lived humoral immune memory in humans.

Highlights

Blood samples were collected approximately 1 month after the onset of symptoms from 77 individuals who were convalescing from COVID-19
In contrast to the anti-S antibody titres, IgG titres against the 2019–2020 inactivated seasonal influenza virus vaccine were detected in all control individuals and individuals who were convalescing from COVID-19, and declined much more gradually, if at all over the course of the study, with mean titres decreasing from 8.0 to 7.9 and 7.9 to 7.8 across the 1-to-4-month and 4-to-11-month intervals after symptom onset, respectively (Fig. 1b)
To investigate whether individuals who had recovered from COVID-19 developed a virus-specific long-lived bone marrow plasma cells (BMPCs) compartment, we examined bone marrow aspirates obtained approximately 7 and 11 months after infection for anti-SARS-CoV-2 S-specific BMPCs

Summary

Discussion

This study sought to determine whether infection with SARS-CoV-2 induces antigen-specific long-lived BMPCs in humans. We detected no S-binding cells among plasmablasts in blood samples collected at the same time as the bone marrow aspirates by ELISpot or flow cytometry in any of the convalescent or control samples Together, these data indicate that mild SARS-CoV-2 infection induces a long-lived BMPC response. Our data suggest that SARS-CoV-2 infection induces a germinal centre response in humans because long-lived BMPCs are thought to be predominantly germinal-centre-derived. Our data provide strong evidence that SARS-CoV-2 infection in humans robustly establishes the two arms of humoral immune memory: long-lived BMPCs and memory B cells. J. et al Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

Methods

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Methodology