With the use of deep immune profiling, we identified three immunotypes in hospitalized COVID-19 patients: (i) robust activation and proliferation of CD4 T cells, relative lack of cTFH cells, modest activation of EMRA-like cells, highly activated or exhausted CD8 T cells, and a signature of T-bet+ PBs (immunotype 1); (ii) Tbetbright effector-like CD8 T cell responses, less robust CD4 T cell responses, and Ki67+ PBs and memory B cells (immunotype 2); and (iii) an immunotype largely lacking detectable lymphocyte response to infection, which suggests a failure of immune activation (immunotype 3). Here, CD4 is linked to COVID-19.