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

2020; Nature Portfolio; Volume: 21; Issue: 12 Linguagem: Inglês

10.1038/s41590-020-00814-z

1529-2916

Matthew C. Woodruff, Richard P. Ramonell, Doan C. Nguyen, Kevin S. Cashman, Ankur Singh Saini, Natalie S. Haddad, Ariel M. Ley, Shuya Kyu, J. Christina Howell, Tuğba Öztürk, Saeyun Lee, Naveenchandra Suryadevara, James Brett Case, Regina Bugrovsky, Weirong Chen, Jacob Estrada, Andrea Morrison-Porter, Andrew Derrico, Fabliha A. Anam, Monika Sharma, Henry M. Wu, Sang Le, Scott A. Jenks, Christopher M. Tipton, Bashar S. Staitieh, John L. Daiss, Eliver Ghosn, Michael Diamond, Robert H. Carnahan, James E. Crowe, William T. Hu, F. Eun‐Hyung Lee, Igñacio Sanz,

Long-Term Effects of COVID-19

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. Sanz and colleagues examine B cell subsets in a cohort of patients with COVID-19. Severely ill patients have higher frequencies of activated extrafollicular T-bet+ B cells that form antibody-secreting cells, the majority of which express germline sequences and are reminiscent of antibody responses observed in patients with systemic lupus erythematosus during flares.