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

• Type of Material: Article
• Authors: Matthew Woodruff, Emory University; Richard Ramonell, Emory University; Doan Nguyen, Emory University; Kevin S. Cashman, Emory University; Ankur Saini, Emory University; Natalie S. Haddad, Emory University; Ariel M. Ley, Emory University; Shuya Kyu, Emory University; J. Christina Howell, Emory University; Tugba Ozturk, Emory University; Saeyun Lee, Emory University; Naveenchandra Suryadevara, Vanderbilt University; James Brett Case, Washington University; Regina Bugrovsky, Emory University; Weirong Chen, Emory University; Jacob Estrada, Emory University; Andrea Morrison-Porter, Emory University; Andrew Derrico, Emory University; Fabliha A. Anam, Emory University; Monika Sharma, Emory University; Henry Wu, Emory University; Sang N. Le, Emory University; Scott Jenks, Emory University; Christopher Tipton, Emory University; Bashar Staitieh, Emory University; John L. Daiss, MicroB-plex, Inc.; Eliver Ghosn, Emory University; Michael S. Diamond, Washington University; Robert H. Carnahan, Vanderbilt University; James E. Crowe, Vanderbilt University; William Hu, Emory University; Frances Lee, Emory University; Ignacio Sanz, Emory University
• Language: English
• Date: 2020-10-07
• Publisher: NATURE PORTFOLIO
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2020
• Final Published Version (URL): http://dx.doi.org/10.1038/s41590-020-00814-z
• Title of Journal or Parent Work: NATURE IMMUNOLOGY
• Volume: 21
• Issue: 12
• Start Page: 1506
• End Page: +
• Grant/Funding Information: This work was supported by National Institutes of Health grants UL TR000424 (Emory Library IT), R01-AG054991 (to W.T.H.), U19-AI110483 Emory Autoimmunity Center of Excellence (to I.S.), P01-AI125180-01 (to I.S. and F.E.-H.L.), R37-AI049660 (to I.S.), 1R01AI121252 (to F.E.-H.L.), 1U01AI141993 (to F.E.-H.L.), R01 AI127828 (to J.E.C. and M.S.D.) and T32-HL116271-07 (to R.P.R.); HHS/NIAID/NIH contract 75N93019C00074 (to J.E.C.); Defense Advanced Research Project Agency grant HR001117S0019 (to J.E.C.); the Dolly Parton COVID-19 Research Fund at Vanderbilt; and a Fast Grants Award (to J.E.C.)
• Keywords: Science & Technology; EFFECTOR; ACTIVATION; POPULATION; DENGUE VIRUS-INFECTION; SOMATIC HYPERMUTATION; Immunology; Life Sciences & Biomedicine
• Research Categories: Biology, Virology; Health Sciences, Immunology

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.