# name
OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2

# metadata.dc.description.abstract[].value
Recessive deficiency in 2',5' -oligoadenylate synthetase (OAS) or RNase L can cause systemic inflammation in children with SARS-CoV-2 infection, but its role in adult respiratory disease is unclear. We analyzed rare OAS1/OAS3 variants and the common OAS1 rs10774671 polymorphism in 342 COVID-19 patients, assessing enzymatic activity, RNase L activation, viral replication, and inflammation in cell systems and Oas3-deficient mice. Rare heterozygous variants showed impaired RNase L activation but were not enriched in pneumonia cases. In contrast, the rs10774671 A/A genotype (OAS1-p42 isoform) was associated with severe disease (OR = 2.28; 95% CI = 1.13-4.58; p = 0.0107) and reduced viral control despite intact RNase L activation. OAS3 and OAS1-p46 isoform limited viral replication and inflammatory responses, whereas Oas3-deficient mice showed increased cytokines. These findings suggest that common OAS1 variation influences COVID-19 severity, while rare OAS variants may affect inflammation regulation rather than respiratory pathology.

# metadata.dc.rights[].value
cc-by-nc-nd (c) DeDiego, Marta L. et al., 2025

# metadata.dc.source[].value
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

# metadata.dc.subject.classification[].value
Malalties de l'aparell respiratori en els infants

# metadata.dc.title[].value
OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2