Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 25;26(10):107735.
doi: 10.1016/j.isci.2023.107735. eCollection 2023 Oct 20.

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

Manuel Corpas  1   2   3   4 , Carmen de Mendoza  5 , Víctor Moreno-Torres  3   5 , Ilduara Pintos  5 , Pedro Seoane  6   7 , James R Perkins  6   7   8 , Juan A G Ranea  6   7   8   9 , Segun Fatumo  10   11   12 , Tamas Korcsmaros  13 , José Manuel Martín-Villa  14 , Pablo Barreiro  3   15 , Octavio Corral  3 , Vicente Soriano  3
Affiliations

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

Manuel Corpas et al. iScience. .

Abstract

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.

Keywords: Genetics; Genomics; Immunology; Virology.

PubMed Disclaimer

Conflict of interest statement

At the time of writing, M.C. is associated with Cambridge Precision Medicine Limited.

Figures

None
Graphical abstract
Figure 1
Figure 1
Number of patients affected with symptoms in our highly selected population Determinants of severe COVID-19 and major clinical phenotypes with numbers referring to patients with severe COVID-19 in our study population within each group.
Figure 2
Figure 2
Flow chart illustrating samples origin, filtering, and data analysis (Bioinformatics workflow) Here, we describe the different steps taken to analyze the patient data and come up with our variants of concern.
Figure 3
Figure 3
Country of birth for the 98 cases with severe COVID-19 enrolled in the study (Case Cohort) Overall 19 individuals were born outside of Spain.
Figure 4
Figure 4
Gene cluster enrichment annotations Results from functional enrichment analysis of top affected genes. The T cell receptor cluster enrichment score (DAVID Enrichment Score: 5.21) is the top scoring functional cluster, followed by epidermal growth factor (1.00) and ANK repeat (0.99).
See this image and copyright information in PMC

References

    1. Soriano V., Barreiro P. Why such excess of mortality for COVID-19 in Spain? Ther. Adv. Infect. Dis. 2020;7 2049936120932755. - PMC - PubMed
    1. Moreno-Torres V., de la Fuente S., Mills P., Muñoz A., Muñez E., Ramos A., Fernández-Cruz A., Arias A., Pintos I., Vargas J.A., et al. Major determinants of death in patients hospitalized with COVID-19 during the first epidemic wave in Madrid, Spain. Medicine. 2021;100:e25634. - PMC - PubMed
    1. Poletti P., Tirani M., Cereda D., Trentini F., Guzzetta G., Sabatino G., Marziano V., Castrofino A., Grosso F., Del Castillo G., et al. Association of Age With Likelihood of Developing Symptoms and Critical Disease Among Close Contacts Exposed to Patients With Confirmed SARS-CoV-2 Infection in Italy. JAMA Netw. Open. 2021;4:e211085. - PMC - PubMed
    1. CDC . Centers for Disease Control and Prevention; 2022. Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Professionals.https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingco... - PubMed
    1. COVID-19 Host Genetics Initiative The COVID-19 Host Genetics Initiative (2020). The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur. J. Hum. Genet. 2020;28:715–718. doi: 10.1038/s41431-020-0636-6. - DOI - PMC - PubMed

LinkOut - more resources