CD4 and COVID-19: In this study, focused on pathogen-specific CD4+ T cell responses, our aims were to (a) compare the profile of preexisting SARS-CoV-2 cross-reactive CD4+ T cells and COVID-19–induced CD4+ T cells, (b) define the relationship between COVID-19 severity and the SARS-CoV-2–specific CD4+ T cell response, (c) investigate the impact of HIV and/or active TB coinfection on the SARS-CoV-2–specific CD4+ T cell response, and (d) assess the effect of COVID-19 on the M. tuberculosis–specific CD4+ T cell response.