Covid-19 Immune Signatures Reveal Stable Antiviral T-Cell Function Despite Declining Humoral Responses

To investigate the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell immunity and its relationship with antibody levels and pre-existing immunity against endemic human coronaviruses (huCoV) during disease and beyond, we analyzed patients with recovered (RC, n=178) and active Coronavirus Disease-2019 (COVID-19; AC, n=10) and healthy donors (HD, n=58). Overall, ACs had highest SARS-CoV-2 antibody levels against nucleocapsid (N) and spike (S) proteins but reduced antiviral T-cell immunity, whereas in RCs, antibody levels partially correlated with SARS-CoV-2-specific T-cell frequencies. Interestingly, humoral responses declined throughout convalescence, whereas T-cell immunity remained stable. RCs exhibited polyfunctional, mainly IFN-γ-secreting CD4 + effector memory T-cell responses. Humoral and cellular response towards huCoV strains in RCs with strong SARS-CoV-2 T-cell immunity implies a protective role of pre-existing immunity against huCoV. This study provides essential evidence-based data about stable protective T-cell immunity during disease and recovery which is essential to guide diagnosis and treatment of COVID-19.