Despite advanced knowledge on the SARS-CoV-2-induced immunity, a deeper understanding of how virus-specific responses are assembled upon infection is necessary. Therefore, the present work investigates the MHC-restricted virus-specific responses of acute and post-acute COVID-19 patients. Our results indicate that convalescent individuals displayed and maintained higher counts of effector memory, and TEMRA CD4+ T and CD8+ T cells as compared to severe COVID-19. Mild COVID-19 displayed a higher early activation profile in memory subsets as compared to severe and convalescent individuals. Regarding the virus-specific T cell responses, SARS-CoV-2 nucleocapsid protein (N) arose as a major target of CD8+ T cells in convalescent HLA-A*2+ individuals, adding to the specific cellular response mediated by the spike (S) protein. Unsupervised analysis enabled the unbiased clustering of lymphocytes and the assessment of differential expression of CD69, production of intracellular IFN-γ, and reactivity to HLA-A*02 tetramers bearing N or S peptides. Furthermore, cell clones targeting S and N proteins of SARS-CoV-2 undergo cellular expansion in HLA-A*02+ convalescent individuals following in vitro antigenic recall by stimulation with inactivated SARS-CoV-2 and viral proteins. Convalescent from COVID-19 presents higher connectivity of the overall immune response in comparison to the acute phase, regardless of disease severity. Collectively, our data shed new light on the role of the protein N-mediated immunity against SARS-CoV-2 in patients from one of the most affected areas in Brazil.
Lopes-Ribeiro et al. (Sun,) studied this question.