Age and Latent Cytomegalovirus Infection Do Not Affect the Magnitude of De Novo SARS‐CoV‐2‐Specific CD8 ⁺ T Cell Responses

Immunosenescence, age-related immune dysregulation, reduces immunity upon vaccinations and infections. Cytomegalovirus (CMV) infection results in declining naïve (T_naïve) and increasing terminally differentiated (T_emra) T cell populations, further aggravating immune aging. Both immunosenescence and CMV have been speculated to hamper the formation of protective T-cell immunity against novel or emerging pathogens. The SARS-CoV-2 pandemic presented a unique opportunity to examine the impact of age and/or CMV on the generation of de novo SARS-CoV-2-specific CD8⁺ T cell responses in 40 younger (22-40 years) and 37 older (50-66 years) convalescent individuals. Heterotetramer combinatorial coding combined with phenotypic markers were used to study 35 SARS-CoV-2 epitope-specific CD8⁺ T cell populations directly ex vivo. Neither age nor CMV affected SARS-CoV-2-specific CD8⁺ T cell frequencies, despite reduced total CD8⁺ T_naïve cells in older CMV^- and CMV⁺ individuals. Robust SARS-CoV-2-specific central memory CD8⁺ T (T_cm) responses were detected in younger and older adults regardless of CMV status. Our data demonstrate that immune aging and CMV status did not impact the SARS-CoV-2-specific CD8⁺ T cell response. However, SARS-CoV-2-specific CD8⁺ T cells of older CMV^- individuals displayed the lowest stem cell memory (T_scm), highest T_emra and PD1⁺ populations, suggesting that age, not CMV, may impact long-term SARS-CoV-2 immunity.