A striking feature of some patients with strong T and B cell activation and proliferation was the durability of this response. This T and B activation was interesting considering clinical lymphopenia in many patients. This lymphopenia, however, was preferential for CD8 T cells. It may be notable that such focal lymphopenia preferentially affecting CD8 T cells is also a feature of acute Ebola infection of macaques and is associated with CD95 expression and severe disease (55). Indeed CD95 was associated with activated T cell clusters in COVID-19 disease. Nevertheless, the frequency of the KI67+ or CD38+HLA-DR+ CD8 and CD4 T cell responses in COVID-19 patients was similar in magnitude to other acute viral infections or live attenuated vaccines in humans (47–49). However, during many acute viral infections, peak CD8 or CD4 T cell responses and the window of detectable PB in peripheral blood are relatively short (43, 56, 57). The stability of CD8 and CD4 T cell activation and PB responses during COVID-19 disease suggests a prolonged period of peak immune responses at the time of hospitalization or perhaps a failure to appropriately down-regulate responses in some patients. These ideas would fit with an overaggressive immune response and/or “cytokine storm” (2) in this subset of patients. Indeed, in some patients, we found elevated serum cytokines and that stimulation of T cells in vitro provoked cytokines and chemokines capable of activating and recruiting myeloid cells. A key question will be how to identify these patients for selected immune regulatory treatment while avoiding treating patients with already weak T and B cell responses.