Sekine et al. conducted a comprehensive study to map the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in individuals with varying levels of exposure, infection, and COVID-19 severity. They found that acute-phase SARS-CoV-2-specific T cells displayed an activated cytotoxic phenotype, while convalescent-phase T cells generated broad responses with a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in seronegative individuals, including those with asymptomatic or mild COVID-19. The study suggests that natural exposure or infection may elicit robust memory T cell responses that could prevent recurrent episodes of severe COVID-19.Sekine et al. conducted a comprehensive study to map the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in individuals with varying levels of exposure, infection, and COVID-19 severity. They found that acute-phase SARS-CoV-2-specific T cells displayed an activated cytotoxic phenotype, while convalescent-phase T cells generated broad responses with a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in seronegative individuals, including those with asymptomatic or mild COVID-19. The study suggests that natural exposure or infection may elicit robust memory T cell responses that could prevent recurrent episodes of severe COVID-19.