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

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. © 2023 The Authors.

Citation

Manuel Corpas, Carmen de Mendoza, Víctor Moreno-Torres, Ilduara Pintos, Pedro Seoane, James R Perkins, Juan A G Ranea, Segun Fatumo, Tamas Korcsmaros, José Manuel Martín-Villa, Pablo Barreiro, Octavio Corral, Vicente Soriano. Genetic signature detected in T cell receptors from patients with severe COVID-19. iScience. 2023 Oct 20;26(10):107735

PMID: 37720084

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