Highly functional Cellular Immunity in SARS-CoV-2 Non-Seroconvertors is associated with immune protection

Kilpeläinen, Athina; Jimenez-Moyano, Esther; Blanch-Lombarte, Oscar; Ouchi, Dan; Peña, Ruth; Quirant-Sanchez, Bibiana; Chamorro, Anna; Blanco, Ignacio; Martínez-Caceres, Eva; Paredes, Roger; Mateu, Lourdes; Carrillo, Jorge; Blanco, Julià ; Brander, Christian; Massanella, Marta; Clotet, Bonaventura; Prado, Julia G.

The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (NSC) recovered from infection. We performed an immune comparative analysis of SARS-CoV-2 infected individuals stratified by the absence or presence of seroconversion and disease severity. We report high levels of total naïve and low effector CD8+ T cells in NSC. Moreover, polyfunctional Nucleocapsid (NP)-specific CD8+ T-cell responses, as well as reduced levels of T-cell activation monitored by PD-1 and activation-induced markers, were distinctive immunological traits in NSC. Longitudinal data support the stability of the NSC phenotype over three months. Our results implicate highly functional SARS-CoV-2 Spike and NP T-cell responses with low immune activation in protection from disease severity in the absence of seroconversion. SUMMARY To understand SARS-CoV-2 specific T-cell immunity in the absence of seroconversion, we characterized immunological features of Non-Seroconvertors recovered from infection. Highly functional specific T-cell responses and low immune activation were determinants of immune protection from severe disease.