Rare host variants in ciliary expressed genes contribute to COVID-19 severity in Bulgarian patients.
COVID-19 severity and outcome
Cilia dysfunction
Host genetic variants
Rare protein-coding variants
SARS-CoV-2
WES
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 08 2024
22 08 2024
Historique:
received:
30
04
2024
accepted:
19
08
2024
medline:
23
8
2024
pubmed:
23
8
2024
entrez:
22
8
2024
Statut:
epublish
Résumé
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a pneumonia with extremely heterogeneous clinical presentation, ranging from asymptomatic to severely ill patients. Previous studies have reported links between the presence of host genetic variants and the outcome of the COVID-19 infection. In our study, we used whole exome sequencing in a cohort of 444 SARS-CoV-2 patients, admitted to hospital in the period October-2020-April-2022, to search for associations between rare pathogenic/potentially pathogenic variants and COVID-19 progression. We used gene prioritization-based analysis in genes that have been reported by host genetic studies. Although we did not identify correlation between the presence of rare pathogenic variants and COVID-19 outcome, in critically ill patients we detected known mutations in a number of genes associated with severe disease related to cardiovascular disease, primary ciliary dyskinesia, cystic fibrosis, DNA damage repair response, coagulation, primary immune disorder, hemoglobin subunit β, and others. Additionally, we report 93 novel pathogenic variants found in severely infected patients who required intubation or died. A network analysis showed main component, consisting of 13 highly interconnected genes related to epithelial cilium. In conclusion, we have detected rare pathogenic host variants that may have influenced the COVID-19 outcome in Bulgarian patients.
Identifiants
pubmed: 39174791
doi: 10.1038/s41598-024-70514-3
pii: 10.1038/s41598-024-70514-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
19487Subventions
Organisme : National Science Fund of Bulgarian Ministry of Education and Science; Bulgarian Ministry of Education and Science
ID : КP-06-DK1/8/2021
Organisme : National Science Fund of Bulgarian Ministry of Education and Science; Bulgarian Ministry of Education and Science
ID : D01/ 285/2019
Organisme : National Science Fund of Bulgarian Ministry of Education and Science; Bulgarian Ministry of Education and Science
ID : D01-395/2020
Organisme : National Science Fund of Bulgarian Ministry of Education and Science; Bulgarian Ministry of Education and Science
ID : D01-302/2021
Informations de copyright
© 2024. The Author(s).
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