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
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 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.
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.
Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity
Carolyn Rydyznski Moderbacher ∗ Sydney I. Ramirez ∗ Jennifer M. Dan ∗ Davey M. Smith
Alessandro Sette Shane Crotty
Open AccessPublished:September 16, 2020DOI:https://doi.org/10.1016/j.cell.2020.09.038
Carolyn Rydyznski Moderbacher ∗ Sydney I. Ramirez ∗ Jennifer M. Dan ∗ Davey M. Smith
Alessandro Sette Shane Crotty
Open AccessPublished:September 16, 2020DOI:https://doi.org/10.1016/j.cell.2020.09.038
Good explainer here: An ‘uncoordinated’ immune response may explain why COVID-19 strikes some hard, particularly the elderly By Jon Cohen Sep. 16, 2020 , 2:00 PM
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