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and RVO: 68378050-KAV-NPUI, for their support with the confocal imaging and image analysis presented herein. Marie-Laure Niepon at the Image platform at Institute de la Vision (Paris, France) is thanked for slide scanning. The authors also want to thank to Dana Ungerova, Eva Suchanova and Anna Smrckova for their help with experiments and to Jan Jakubik, Vladimir Dolezal, Alena Randakova and Ornela Kljakic for their reading and valuable comments on the manuscript.

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Age is associated with changes in the immune system which increase the risk for severe COVID‐19. Here, we investigate SARS‐CoV‐2‐reactive CD4 T cells from individuals recovered from SARS‐CoV‐2 infection with mild COVID‐19 symptoms after 3, 6 and 9 months using incubation with SARS‐CoV‐2 S1, S2 and N‐peptide pools, followed by flow cytometry for a Th1‐activation profile or proliferation analyses. We found that SARS‐CoV‐2‐reactive CD4 T cells are decreasing on average after 9 months but highly polyfunctional CD4 T cells can peak after 6‐month recovery. We show that individuals older than 60 years of age have significantly more SARS‐CoV‐2‐reactive T cells in their blood after 3 months of recovery compared to younger individuals and that the percentage of SARS‐CoV‐2‐reactive Th1‐directed CD4 T cells in the blood of mild‐COVID‐19‐recovered individuals correlates with age. Finally, we show that individuals over the age of 40 have significantly increased the amounts of highly polyfunctional SARS‐CoV‐2‐S‐peptide‐reactive CD4 T cells, compared to SARS‐CoV‐2 naïve individuals, than those under the age of 40. These findings suggest that in individuals recovered from mild COVID‐19, increased age is associated with significantly more highly polyfunctional SARS‐CoV‐2‐reactive CD4 T cells with a Th1‐profile and that these responses persist over time.