Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity

Moderbacher, Carolyn Rydyznski; Ramirez, Sydney I.; Dan, Jennifer M.; Grifoni, Alba; Hastie, Kathryn M.; Weiskopf, Daniela; Belanger, Simon; Abbott, Robert K.; Kim, Christina; Choi, Jinyong; Kato, Yu; Crotty, Eleanor G.; Kim, Cheryl; Rawlings, Stephen A.; Mateus, Jose; Victor Tse, Long Ping; Frazier, April; Baric, Ralph; Peters, Bjoern; Greenbaum, Jason; Saphire, Erica Ollmann; Smith, Davey M.; Sette, Alessandro; Crotty, Shane

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 ageing 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 ageing and impaired adaptive immune responses to SARS-CoV-2.