Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity

著者: Carolyn Rydyznski Moderbacher, Sydney I. Ramirez, Jennifer M. Dan, Alba Grifoni, Kathryn M. Hastie, Daniela Weiskopf, Simon Bélanger, Robert Abbott, Christina Kim, Jinyong Choi, Yu Kato, Eleanor G. Crotty, Cheryl Kim, Stephen A. Rawlings, José Mateus, Longping V. Tse, April Frazier, Ralph S. Baric, Bjoern Peters, Jason Greenbaum, Erica Ollmann Saphire, Davey M. Smith, Alessandro Sette, Shane Crotty - Cell 2020 被引用: 1,987

Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4 + and CD8 + T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4 + and CD8 + T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4 + and CD8 + T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4 + T cell, CD8 + T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.