Published on Wed Jul 28 2021

Altered pre-existing SARS-CoV-2-specific T cell responses in elderly individuals

Taira, N., Toguchi, S., Miyagi, M., Mori, T., Tomori, H., Oshiro, K., Tamai, O., Kina, M., Miyagi, M., Tamaki, K., Collins, M. K., Ishikawa, H.

Pre-existing SARS-CoV-2-specific T cells, but not antibodies, have been detected in some unexposed individuals. This may account for some of the diversity in clinical outcomes ranging from asymptomatic infection to severe COVID-19.

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Abstract

Pre-existing SARS-CoV-2-specific T cells, but not antibodies, have been detected in some unexposed individuals. This may account for some of the diversity in clinical outcomes ranging from asymptomatic infection to severe COVID-19. Although age is a risk factor for COVID-19, how age affects SARS-CoV-2-specific T cell responses remains unknown. We found that some pre-existing T cell responses to specific SARS-CoV-2 proteins, Spike (S) and Nucleoprotein (N), were significantly lower in elderly donors (>70 years old) who were seronegative for S than in young donors. However, substantial pre-existing T cell responses to the viral membrane (M) protein were detected in some elderly donors. These responses likely compensate for loss of T cell responses specific to S and N. In contrast, young and elderly donors exhibited comparable T cell responses to S, N, and M proteins after infection with SARS-CoV-2. M-specific responses were mediated by CD4 T cells producing interferon-gamma in both seronegative and seropositive individuals. T cells in seronegative elderly donors responded to various M-derived peptides, while the response after SARS-CoV-2 infection was apparently focused on a single peptide. These data suggest that diversity of target antigen repertoire for pre-existing SARS-CoV-2-specific T cells declines with age, but the magnitude of pre-existing T cell responses is maintained by T cells reactive to specific viral proteins such as M. A better understanding of the role of pre-existing SARS-CoV-2-specific T cells that are less susceptible to age-related loss may contribute to development of more effective vaccines for elderly people.