SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses (HCoV). However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response and antibody levels is needed.
We assayed SARS-CoV-2 specific T-cell response in 103 participants. Thirty-seven (18 mild and 19 severe) were hospitalized during acute COVID-19 and 33 were recruited seven months after SARS-CoV-2 infection (19 previously hospitalized (H) and 14 non-hospitalized (NH) during acute infection). Pre-COVID-19 healthy donors (HD, n=33) were included. PBMCs were stimulated with Spike (S) and Nucleocapside (N) SARS-COV-2 peptide pools. Likewise, an optimized peptide pool of HCoV S protein was used in HD. T-cell polyfunctionality by intracellular cytokine staining (IFN-?, IL-2, TNF-?, CD107a and perforin (PRF)) was assayed by multiparametric flow cytometry together with measurements of T cell subsets, activation, exhaustion and senescence. Anti-S SARS-CoV-2 and HCoV IgG titers and pro-inflammatory markers were measured in plasma. Non-parametric statistic was used for the analysis.
Mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels (e.g., N-specific EM CD4+ IL-2+ T-cell, r=-0.594, p=0.004). However, only IFN-? combinations without PRF production was mostly observed for severe disease (e.g., S-specific TEMRA CD4+ CD107a-IFN-?+IL-2-PRF-TNF-?- T-cells, p=0.008). Moreover, this response was long-lasting seven months after SARS-CoV-2 infection. Both NH and H individuals presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only H individuals showed a T-cell exhaustion profile (e.g., TEMRA CD4+ TIGIT+ T cells, p=0.0004). Combinations including IL-2, but not IFN-?, in response to HCoV S protein, were associated with SARS-CoV-2 S-specific T-cell response in HD (e.g., S-specific CM CD8+ CD107a-IFN-?-IL-2+PRF-TNF-?- T-cells, r=5414, p=0.001).
T-cell polyfunctionality features were associated with disease severity. Moreover, T-cell response was robust seven months after infection, although previously hospitalized patients showed signs of exhaustion. SARS-CoV-2 and HCoV immune cross-reactivity have implications for protective immunity against SARS-CoV-2 to design new prototypes of vaccines in order to achieve of broader long-lasting protection against COVID-19.