Zeng et al. (2020) observed CD4+ T cell lymphopenia in all severe and fatal cases with SARS-CoV-2 infection in their study. Furthermore, the authors could show that prolonged activation and exhaustion of CD8+ T cells were associated with COVID-19 severity. In single-cell transcriptomic analyses, encompassing over 80,000 virus-reactive CD8+ T single cells, Kusnadi et al. (2021) could show that SARS-CoV-2-reactive CD8+ cells exhibited exhausted phenotypes with a decreased capacity to produce cytokines in severely ill COVID-19 patients. This evidence concerns the gene CD4 and COVID-19.