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

Abstract

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.

Highlights

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  Adaptive immune responses limit COVID-19 disease severity

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  Multiple coordinated arms of adaptive immunity control better than partial responses

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  CXCL10 may be a biomarker of impaired T cell responses in acute COVID-19

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  Aging and scarcity of naive T cells may be linked risk factors for severe COVID-19

Abstract

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.