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- Title
The TNFRSF13C H159Y Variant Is Associated with Severe COVID-19: A Retrospective Study of 500 Patients from Southern Italy.
- Authors
Russo, Roberta; Andolfo, Immacolata; Lasorsa, Vito Alessandro; Cantalupo, Sueva; Marra, Roberta; Frisso, Giulia; Abete, Pasquale; Cassese, Gian Marco; Servillo, Giuseppe; Esposito, Gabriella; Gentile, Ivan; Piscopo, Carmelo; Della Monica, Matteo; Fiorentino, Giuseppe; Russo, Giuseppe; Cerino, Pellegrino; Buonerba, Carlo; Pierri, Biancamaria; Zollo, Massimo; Iolascon, Achille
- Abstract
To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.
- Subjects
ITALY; COVID-19; SARS-CoV-2; HUMORAL immunity; HOSPITAL patients; RETROSPECTIVE studies; B cells; EXOMES
- Publication
Genes, 2021, Vol 13, Issue 6, p881
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes12060881