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

## TL;DR

Age and CMV infection do not reduce the strength of CD8+ T cell responses to SARS-CoV-2, though age may affect long-term immunity.

## Contribution

Demonstrates that immune aging and CMV status do not impair de novo SARS-CoV-2-specific CD8+ T cell responses in convalescent individuals.

## Key findings

- Age and CMV status did not affect SARS-CoV-2-specific CD8+ T cell frequencies in convalescent individuals.
- Robust central memory CD8+ T cell responses were observed in both younger and older adults regardless of CMV status.
- Older CMV- individuals showed the lowest stem cell memory and highest Temra and PD1+ CD8+ T cell populations.

## Abstract

Immunosenescence, age‐related immune dysregulation, reduces immunity upon vaccinations and infections. Cytomegalovirus (CMV) infection results in declining naïve (Tnaïve) and increasing terminally differentiated (Temra) 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+ Tnaïve cells in older CMV‐ and CMV+ individuals. Robust SARS‐CoV‐2‐specific central memory CD8+ T (Tcm) 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 (Tscm), highest Temra and PD1+ populations, suggesting that age, not CMV, may impact long‐term SARS‐CoV‐2 immunity.

Immunosenescence and cytomegalovirus infection are suggested to impair protective immunity against novel pathogens. Despite reduced total CD8+ Tnaïve cells in older CMV‐ and CMV+ individuals, our study found a broad and robust memory SARS‐CoV‐2‐specific CD8+ T cell response in both younger and older convalescent COVID‐19 donors regardless of CMV status.