Mazzoni A, Salvati L, Maggi L, et al. - Given the emergence of coronavirus disease 19 (COVID-19) caused by SARS-CoV-2, researchers sought to determine the mechanisms regulating pathogen elimination, immunity, and pathology that may aid in better characterizing disease progression and widening of the spectrum of therapeutic options. Performing a flow cytometric characterization of immune cell subsets from 30 patients with COVID-19, they identified reduced numbers of circulating T, B, and NK cells and a skewing of CD8+ T cells toward a terminally differentiated/senescent phenotype among patients with COVID-19. In agreement, reduced antiviral cytokine production capability was observed in CD4+ T and CD8+ T, and also in NK cells. Moreover, patients with COVID-19, particularly those who required intensive care, exhibited a reduced cytotoxic potential. In addition, the latter group of patients displayed raised serum IL-6 levels that inversely linked to the frequency of granzyme A–expressing NK cells. The cytotoxic potential of NK cells restored with off-label treatment with tocilizumab. Findings thereby indicated correlation between IL-6 serum levels and the impairment of cytotoxic activity suggesting the possibility that targeting this cytokine may restore antiviral mechanisms.