tetano
Editor, Senior Moderator
Cell
. 2020 Sep 16;S0092-8674(20)31235-6.
doi: 10.1016/j.cell.2020.09.038. Online ahead of print.
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity
Carolyn Rydyznski Moderbacher[SUP] 1 [/SUP], Sydney I Ramirez[SUP] 2 [/SUP], Jennifer M Dan[SUP] 2 [/SUP], Alba Grifoni[SUP] 1 [/SUP], Kathryn M Hastie[SUP] 1 [/SUP], Daniela Weiskopf[SUP] 1 [/SUP], Simon Belanger[SUP] 1 [/SUP], Robert K Abbott[SUP] 1 [/SUP], Christina Kim[SUP] 1 [/SUP], Jinyong Choi[SUP] 1 [/SUP], Yu Kato[SUP] 1 [/SUP], Eleanor G Crotty[SUP] 1 [/SUP], Cheryl Kim[SUP] 3 [/SUP], Stephen A Rawlings[SUP] 4 [/SUP], Jose Mateus[SUP] 1 [/SUP], Long Ping Victor Tse[SUP] 5 [/SUP], April Frazier[SUP] 1 [/SUP], Ralph Baric[SUP] 6 [/SUP], Bjoern Peters[SUP] 1 [/SUP], Jason Greenbaum[SUP] 1 [/SUP], Erica Ollmann Saphire[SUP] 2 [/SUP], Davey M Smith[SUP] 4 [/SUP], Alessandro Sette[SUP] 7 [/SUP], Shane Crotty[SUP] 8 [/SUP]
Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] T cell, CD8[SUP]+[/SUP] 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.
Keywords: CD4; CD8; CXCL10; IP-10; Spike; T cells; adaptive immunity; antibody; coronavirus; epitopes; neutralizing antibodies.
. 2020 Sep 16;S0092-8674(20)31235-6.
doi: 10.1016/j.cell.2020.09.038. Online ahead of print.
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity
Carolyn Rydyznski Moderbacher[SUP] 1 [/SUP], Sydney I Ramirez[SUP] 2 [/SUP], Jennifer M Dan[SUP] 2 [/SUP], Alba Grifoni[SUP] 1 [/SUP], Kathryn M Hastie[SUP] 1 [/SUP], Daniela Weiskopf[SUP] 1 [/SUP], Simon Belanger[SUP] 1 [/SUP], Robert K Abbott[SUP] 1 [/SUP], Christina Kim[SUP] 1 [/SUP], Jinyong Choi[SUP] 1 [/SUP], Yu Kato[SUP] 1 [/SUP], Eleanor G Crotty[SUP] 1 [/SUP], Cheryl Kim[SUP] 3 [/SUP], Stephen A Rawlings[SUP] 4 [/SUP], Jose Mateus[SUP] 1 [/SUP], Long Ping Victor Tse[SUP] 5 [/SUP], April Frazier[SUP] 1 [/SUP], Ralph Baric[SUP] 6 [/SUP], Bjoern Peters[SUP] 1 [/SUP], Jason Greenbaum[SUP] 1 [/SUP], Erica Ollmann Saphire[SUP] 2 [/SUP], Davey M Smith[SUP] 4 [/SUP], Alessandro Sette[SUP] 7 [/SUP], Shane Crotty[SUP] 8 [/SUP]
Affiliations
- PMID: 33010815
- PMCID: PMC7494270
- DOI: 10.1016/j.cell.2020.09.038
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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[SUP]+[/SUP] T cell, CD8[SUP]+[/SUP] 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.
Keywords: CD4; CD8; CXCL10; IP-10; Spike; T cells; adaptive immunity; antibody; coronavirus; epitopes; neutralizing antibodies.