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Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19

Nicholas Liao

Nat Immunol. 2020 Dec;21(12):1506-1516. doi: 10.1038/s41590-020-00814-z. | PubMed

Matthew C Woodruff1,2, Richard P Ramonell3, Doan C Nguyen3, Kevin S Cashman1, Ankur Singh Saini1, Natalie S Haddad3,4, Ariel M Ley3, Shuya Kyu3, J Christina Howell5, Tugba Ozturk5, Saeyun Lee1,3, Naveenchandra Suryadevara6, James Brett Case7, Regina Bugrovsky1, Weirong Chen1, Jacob Estrada1, Andrea Morrison-Porter3, Andrew Derrico3, Fabliha A Anam1, Monika Sharma1, Henry M Wu8, Sang N Le1,3, Scott A Jenks1,2, Christopher M Tipton1,2, Bashar Staitieh3, John L Daiss4, Eliver Ghosn1, Michael S Diamond7,9,10,11, Robert H Carnahan6,12, James E Crowe Jr6,12, William T Hu5, F Eun-Hyung Lee13, Ignacio Sanz14,15

  1. Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
  2. Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA.
  3. Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA.
  4. MicroB-plex, Atlanta, GA, USA.
  5. Department of Neurology, Emory University, Atlanta, GA, USA.
  6. Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  7. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  8. Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA, USA.
  9. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
  10. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  11. Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
  12. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
  13. Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA, USA. f.e.lee@emory.edu.
  14. Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA. ignacio.sanz@emory.edu.
  15. Emory Autoimmunity Center of Excellence, Emory University, Atlanta, GA, USA. ignacio.sanz@emory.edu.

Abstract

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.

Presented By Matthew Woodruff | ORCID iD