M. Woodruff, R. Ramonell, D. Nguyen, K. Cashman, A. Saini, N. Haddad, A. Ley, S. Kyu, J. Howell, T. Ozturk, Saeyun Lee, Naveen Chandra Suryadevara, J. Case, R. Bugrovsky, Weirong Chen, J. Estrada, A. Morrison-Porter, A. Derrico, F. Anam, Monika Sharma, Henry M. Wu, S. Le, S. Jenks, C. Tipton, B. Staitieh, J. Daiss, E. Ghosn, M. Diamond, R. Carnahan, J. Crowe, William T. Hu, F. E. Lee, I. Sanz
Nature immunology, 2020
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.
Cited by 147 publications.
Field of study: Medicine