Genetically determined thymic function affects strength and duration of immune response in COVID patients with pneumonia

Abstract

Thymic activation improves the outcome of COVID-19 patients with severe pneumonia. The <i>rs2204985</i> genetic polymorphism within the <i>TCRA-TCRD</i> locus, which affects thymic output in healthy individuals, was found here to modify SARS-CoV-2-specific immunity and disease severity in COVID-19 patients with severe pneumonia. Forty patients with severe COVID-19 pneumonia were investigated. The GG genotype at the <i>rs2204985</i> locus was associated, independently of age and sex, with stronger and long-lasting anti-SARS-CoV-2 helper and cytotoxic T cell responses 6 months after recovery. The GG genotype was also associated with less severe lung involvement, higher thymic production, and higher counts of blood naïve T lymphocytes, including recent thymic emigrants, and a larger population of activated stem cell memory CD4⁺ T cells. Overall, GG patients developed a more robust and sustained immunity to SARS-CoV-2. Polymorphism at <i>rs2204985</i> locus should be considered as an additional predictive marker of anti-SARS-CoV-2 immune response.