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An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8+ T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2−specific CD8+ and CD4+ T cells in vitro, with CD4+ T cells being robust. We identified two HLAA* 02:01-restricted SARS-CoV-2-specfic CD8+ T cell epitopes, A2/ S269–277 and A2/Orf1ab3183–3191. Using peptide−HLA tetramer enrichment, direct ex vivo assessment of A2/S269 +CD8+ and A2/ Orf1ab3183 +CD8+ populations indicated that A2/S269 +CD8+ T cellswere detected at comparable frequencies (∼1.3 × 10−5) in acute and convalescent HLA-A*02:01+ patients. These frequencies were higher than those found in uninfected HLA-A*02:01+ donors (∼2.5 × 10−6), but low when compared to frequencies for influenza-specific (A2/M158) and Epstein–Barr virus (EBV)-specific (A2/BMLF1280) (∼1.38 × 10−4) populations. Phenotyping A2/S269 +CD8+ T cells from COVID-19 convalescents ex vivo showed that A2/S269 +CD8+ T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8+ T cells expressed granzymes and/or perforin. Furthermore, the bias toward naïve, stem cell memory and central memory A2/S269 +CD8+ T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8+ T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8+ T cell immunity in COVID-19. [ABSTRACT FROM AUTHOR]

An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8 + T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2-specific CD8 + and CD4 + T cells in vitro, with CD4 + T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8 + T cell epitopes, A2/S 269-277 and A2/Orf1ab 3183-3191 Using peptide-HLA tetramer enrichment, direct ex vivo assessment of A2/S 269 + CD8 + and A2/Orf1ab 3183 + CD8 + populations indicated that A2/S 269 + CD8 + T cells were detected at comparable frequencies (∼1.3 × 10 -5 ) in acute and convalescent HLA-A*02:01 + patients. These frequencies were higher than those found in uninfected HLA-A*02:01 + donors (∼2.5 × 10 -6 ), but low when compared to frequencies for influenza-specific (A2/M1 58 ) and Epstein-Barr virus (EBV)-specific (A2/BMLF 1280 ) (∼1.38 × 10 -4 ) populations. Phenotyping A2/S 269 + CD8 + T cells from COVID-19 convalescents ex vivo showed that A2/S 269 + CD8 + T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8 + T cells expressed granzymes and/or perforin. Furthermore, the bias toward naïve, stem cell memory and central memory A2/S 269 + CD8 + T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8 + T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8 + T cell immunity in COVID-19., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)