A Clinical-Genetic Study of COVID-19 Severity: Insights into IFNAR2 and OAS3 Polymorphisms

Abstract

Background: The severity of COVID-19 is influenced by clinical and genetic factors, some of which can worsen patient outcomes. IFNAR2 and OAS3 are potential regulators of innate antiviral immunity, and polymorphisms in these genes may contribute to the variability in COVID-19 severity. However, their precise role remains to be fully elucidated. Objectives: In this study, we investigated the association between clinical factors and two immune-related single nucleotide polymorphisms (SNPs), including IFNAR2 rs2236757 and OAS3 rs10735079, with COVID-19 severity. Methods: This case-control study included a total of 315 patients with confirmed COVID-19 by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), including 209 non-severe and 106 severe cases. Samples were collected between June 2020 and January 2021 from Qazvin. Clinical and demographic parameters were recorded and subjected to statistical analysis to assess their association with disease severity. Genotyping of IFNAR2 rs2236757 and OAS3 rs10735079 polymorphisms was performed using the tetra-primer ARMS-PCR (T-ARMS) method. Results: The clinical factors such as older age, diabetes (27.7%), hypertension (36.8%), cardiovascular disease (17.0%), cough, and dyspnea (82.6%) were significantly associated with COVID-19 severity (P < 0.05). Interestingly, fever (higher in non-severe patients) and smoking (less frequent in severe cases) also showed significant differences between groups. However, no statistically significant association was found between the IFNAR2 rs2236757 and OAS3 rs10735079 polymorphisms and disease severity, although a higher frequency of the OAS3 rs10735079 GG genotype among severe cases suggested a possible trend. Conclusions: These results highlight the predominant role of clinical factors over host genetic variations in determining COVID-19 outcomes, and emphasize the need for larger, population-specific studies along with further investigation of SNPs to clarify the contribution of immune-related genes.