Genetic signature detected in T cell receptors from patients with severe COVID-19

• Published in: iScience Vol. 26; no. 10; p. 107735
• Main Authors: Corpas, Manuel, de Mendoza, Carmen, Moreno-Torres, Víctor, Pintos, Ilduara, Seoane, Pedro, Perkins, James R., Ranea, Juan A.G., Fatumo, Segun, Korcsmaros, Tamas, Martín-Villa, José Manuel, Barreiro, Pablo, Corral, Octavio, Soriano, Vicente
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 20.10.2023; Elsevier
• Subjects: Genetics; Genomics; Immunology; Virology; Genetics; Immunology; Genomics; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107735

Characterization of host genetic factors contributing to COVID-19 severity promises advances on drug discovery to fight the disease. Most genetic analyses to date have identified genome-wide significant associations involving loss-of-function variants for immune response pathways. Despite accumulating evidence supporting a role for T cells in COVID-19 severity, no definitive genetic markers have been found to support an involvement of T cell responses. We analyzed 205 whole exomes from both a well-characterized cohort of hospitalized severe COVID-19 patients and controls. Significantly enriched high impact alleles were found for 25 variants within the T cell receptor beta (TRB) locus on chromosome 7. Although most of these alleles were found in heterozygosis, at least three or more in TRBV6-5, TRBV7-3, TRBV7-6, TRBV7-7, and TRBV10-1 suggested a possible TRB loss of function via compound heterozygosis. This loss-of-function in TRB genes supports suboptimal or dysfunctional T cell responses as a major contributor to severe COVID-19 pathogenesis. [Display omitted] •T cell receptor inactivated genes appear enriched in severe COVID-19 patients•These genes participate in highly specific antigen recognition•Results suggest suboptimal T cell responses in severe SARS-CoV-2 infection Genetics; Immunology; Virology; Genomics