Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
Journal
medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986
Informations de publication
Date de publication:
25 Oct 2022
25 Oct 2022
Historique:
entrez:
3
11
2022
pubmed:
4
11
2022
medline:
4
11
2022
Statut:
epublish
Résumé
We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases. We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis. No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
Sections du résumé
Background
UNASSIGNED
We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.
Methods
UNASSIGNED
We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.
Results
UNASSIGNED
No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was
Conclusions
UNASSIGNED
Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
Identifiants
pubmed: 36324795
doi: 10.1101/2022.10.22.22281221
pmc: PMC9628204
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI088364
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001866
Pays : United States
Commentaires et corrections
Type : UpdateIn