Functional profile, homing and residency of protective T cell immune responses against SARS-CoV-2

Grau-Exposito, J.; Sanchez-Gaona, N.; Massana, N.; Suppi, M.; Astorga-Gamaza, A.; Perea, D.; Rosado, J.; Falco, A.; Kirkegaard, C.; Torrella, A.; Planas, B.; Navarro, J.; Suanzes, P.; Alvarez-de la Sierra, D.; Ayora, A.; Sansano, I.; Esperalba, J.; Andres, C.; Anton, A.; Ramon y Cajal, S.; Almirante, B.; Pujol-Borrell, R.; Falco, V.; Burgos, J.; Buzon, M. J.; Genesca, M.

To inform on the correlates of protection against SARS-CoV-2, we studied T cell functions, migration patterns and apoptosis associated with antigen responses in three groups of patients during acute infection. T cell functional profiles against SARS-CoV-2 depended on the targeted viral protein and clinical outcome. Hospitalization and disease severity were associated with predominant IFNg and IL-4 responses, as well as increased responses against S peptides and apoptosis, while non-hospitalized patients were characterized by IL-10 secretion, to which a particular subset expressing high levels of CCR7 contributed abundantly. Importantly, lung-resident memory T cells were strongly detected in convalescent patients, in which contemporary blood did not reflect tissue resident profiles. Our results suggest that a balanced anti-inflammatory antiviral response promoted by non-spike proteins may be key to favor infection resolution without major complications. Still, these immune responses can migrate and establish in the lung as resident memory T cells, affecting future protection.