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

Author

Listed:
  • Jackson S. Turner

    (Washington University School of Medicine)

  • Wooseob Kim

    (Washington University School of Medicine)

  • Elizaveta Kalaidina

    (Washington University School of Medicine)

  • Charles W. Goss

    (Washington University School of Medicine)

  • Adriana M. Rauseo

    (Washington University School of Medicine)

  • Aaron J. Schmitz

    (Washington University School of Medicine)

  • Lena Hansen

    (Washington University School of Medicine
    University of Bergen)

  • Alem Haile

    (Washington University School of Medicine)

  • Michael K. Klebert

    (Washington University School of Medicine)

  • Iskra Pusic

    (Washington University School of Medicine)

  • Jane A. O’Halloran

    (Washington University School of Medicine)

  • Rachel M. Presti

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Ali H. Ellebedy

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

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 B cells directed against SARS-CoV-2 S were detected in the convalescent individuals. Overall, our results indicate that mild infection with SARS-CoV-2 induces robust antigen-specific, long-lived humoral immune memory in humans.

Suggested Citation

  • Jackson S. Turner & Wooseob Kim & Elizaveta Kalaidina & Charles W. Goss & Adriana M. Rauseo & Aaron J. Schmitz & Lena Hansen & Alem Haile & Michael K. Klebert & Iskra Pusic & Jane A. O’Halloran & Rach, 2021. "SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans," Nature, Nature, vol. 595(7867), pages 421-425, July.
  • Handle: RePEc:nat:nature:v:595:y:2021:i:7867:d:10.1038_s41586-021-03647-4
    DOI: 10.1038/s41586-021-03647-4
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    Cited by:

    1. Helen Ward & Matthew Whitaker & Barnaby Flower & Sonja N. Tang & Christina Atchison & Ara Darzi & Christl A. Donnelly & Alexandra Cann & Peter J. Diggle & Deborah Ashby & Steven Riley & Wendy S. Barcl, 2022. "Population antibody responses following COVID-19 vaccination in 212,102 individuals," Nature Communications, Nature, vol. 13(1), pages 1-6, December.
    2. Dominik Menges & Kyra D. Zens & Tala Ballouz & Nicole Caduff & Daniel Llanas-Cornejo & Hélène E. Aschmann & Anja Domenghino & Céline Pellaton & Matthieu Perreau & Craig Fenwick & Giuseppe Pantaleo & C, 2022. "Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Peter Radvak & Hyung-Joon Kwon & Martina Kosikova & Uriel Ortega-Rodriguez & Ruoxuan Xiang & Je-Nie Phue & Rong-Fong Shen & James Rozzelle & Neeraj Kapoor & Taylor Rabara & Jeff Fairman & Hang Xie, 2021. "SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    4. Marco Mandolesi & Hrishikesh Das & Liset Vries & Yiqiu Yang & Changil Kim & Manojj Dhinakaran & Xaquin Castro Dopico & Julian Fischbach & Sungyong Kim & Mariia V. Guryleva & Monika Àdori & Mark Cherny, 2024. "Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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