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Nat Immunol
. 2020 Oct 7.
doi: 10.1038/s41590-020-00814-z. Online ahead of print.
Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19
Matthew C Woodruff 1 2 , Richard P Ramonell 3 , Doan C Nguyen 3 , Kevin S Cashman 1 , Ankur Singh Saini 1 , Natalie S Haddad 3 4 , Ariel M Ley 3 , Shuya Kyu 3 , J Christina Howell 5 , Tugba Ozturk 5 , Saeyun Lee 1 3 , Naveenchandra Suryadevara 6 , James Brett Case 7 , Regina Bugrovsky 1 , Weirong Chen 1 , Jacob Estrada 1 , Andrea Morrison-Porter 3 , Andrew Derrico 3 , Fabliha A Anam 1 , Monika Sharma 1 , Henry M Wu 8 , Sang N Le 1 3 , Scott A Jenks 1 2 , Christopher M Tipton 1 2 , Bashar Staitieh 3 , John L Daiss 4 , Eliver Ghosn 1 , Michael S Diamond 7 9 10 11 , Robert H Carnahan 6 12 , James E Crowe Jr 6 12 , William T Hu 5 , F Eun-Hyung Lee 13 , Ignacio Sanz 14 15
Affiliations
- PMID: 33028979
- DOI: 10.1038/s41590-020-00814-z
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.