Coordination of cellular responses to SARS-CoV-2 during severe COVID-19 illness

The early cellular and humoral immune responses to SARS-CoV-2 result in a wide range of COVID-19 disease severity. Here we conducted an observational study of these three arms of the immune responses (T, B and NK) to SARS-CoV-2 in 17 patients hospitalized for severe COVID-19 at median of 31 days after first symptoms. We found that the main T cell response was directed against two specific regions of the spike viral protein, called B and E, which are inversely correlated with the expression of the KIR2DL1 inhibitory receptor on NK cells (p = 0.03, and p = 0.0001 respectively). Furthermore, expression of the inhibitory receptor ILT2 on NK cells was only correlated with T cell responses against the specific E region (p = 0.02), suggesting that HLA-G may play a role in the extinction of the NK response to the T cell response. Moreover, the antibody response was mainly directed against the nucleocapsid, whereas the antibody neutralizing response was inversely correlated with the cellular response to spike (p < 0.003). Taken together these data suggest a strong coordination between the innate and adaptive immune responses during the acute phase of infection, which could reflect the further resolution of COVID-19 patients with severe disease.