Summary 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. Graphical Abstract Highlights • Adaptive immune responses limit COVID-19 disease severity • Multiple coordinated arms of adaptive immunity control better than partial responses • CXCL10 may be a biomarker of impaired T cell responses in acute COVID-19 • Aging and scarcity of naive T cells may be linked risk factors for severe COVID-19 Analysis of SARS-CoV-2-specific adaptive immune responses during acute COVID-19 identifies coordination between SARS-CoV-2-specific CD4 T cells and CD8 T cells to limit disease severity. Aged individuals often exhibit uncoordinated adaptive responses, potentially tied to scarcity of naive T cells, highlighting immunologic risk factors linked to disease severity.
【저자키워드】 Adaptive immunity, coronavirus, Neutralizing antibodies, spike, antibody, T cells, CXCL10, IP-10, CD4, CD8, Epitopes, 【초록키워드】 COVID-19, SARS-CoV-2, immune response, Biomarker, adaptive, severe COVID-19, Immunity, aging, knowledge, disease severity, Antibody Response, risk factor, outcomes, protective immunity, response, Adaptive immune response, convalescent, disease, Neutralizing antibody response, Protective, scarcity, connection, individual, COVID-19 disease severity, acute COVID-19, Multiple, responses, Arm, limit, identify, subjects, highlighting, Limited, 【제목키워드】 COVID-19, SARS-CoV-2,