Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

  1. Leticia Kuri-Cervantes
  2. M. Betina Pampena
  3. Wenzhao Meng
  4. Aaron M. Rosenfeld
  5. Caroline A.G. Ittner
  6. Ariel R. Weisman
  7. Roseline Agyekum
  8. Divij Mathew
  9. Amy E. Baxter
  10. Laura Vella
  11. Oliva Kuthuru
  12. Sokratis Apostolidis
  13. Luanne Bershaw
  14. Jeannete Dougherty
  15. Allison R. Greenplate
  16. Ajinkya Pattekar
  17. Justin Kim
  18. Nicholas Han
  19. Sigrid Gouma
  20. Madison E. Weirick
  21. Claudia P. Arevalo
  22. Marcus J. Bolton
  23. Eileen C. Goodwin
  24. Elizabeth M. Anderson
  25. Scott E. Hensley
  26. Tiffanie K. Jones
  27. Nilam S. Mangalmurti
  28. Eline T. Luning Prak
  29. E. John Wherry
  30. Nuala J. Meyer
  31. Michael R. Betts
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Abstract

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2-specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.

One Sentence Summary

Broad immune perturbations in severe COVID-19

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