A large body of evidence suggests functional exhaustion of CD8+ T and CD4+ T cells in the peripheral blood of COVID-19 patients. In some instances, exhaustion markers are concomitantly expressed along with activation and proliferation markers, as discussed above (Diao et al., 2020; Mathew et al., 2020; Mazzoni et al., 2020). Moreover, increased expression of exhaustion-related genes like BATF, IRF4, and CD274 also correlated with disease severity (Hadjadj et al., 2020). Interestingly, increased apoptosis of T cells became evident in severe cases as compared to mild/moderate conditions. Thus, one way to explain lymphocytopenia in COVID-19 patients is that after the onset of symptoms, T cells are primed to overcome the infection. However, in cases where viral infection persists, these cells attain robust activation, which may do more harm than good, as seen in severe and critically ill patients reviewed by Chen and John Wherry (2020). Thus, the exhaustion of these cells precedes robust activation response, and eventually, they get eliminated from the circulation, as has been seen with previous viral infections (Wherry, 2011; Blank et al., 2019). For example, during acute infection by lymphocytic choriomeningitis virus (LCMV), CD8+ T cells were shown to exhibit functional activation status and develop into memory T cells.