Association of IFNAR2 rs2236757 and OAS3 rs10735079 polymorphisms with susceptibility to COVID-19 infection and severity

The clinical course and severity of COVID-19 vary among patients. This study aimed to investigate the association of the interferon receptor ( IFNAR2 ) rs2236757 and oligoadenylate synthetase 3 ( OAS3 ) rs10735079 gene polymorphisms with risk of COVID-19 infection and severity among Palestinian patients. The study was conducted between April and May 2021 on 154 participants that divided into three groups: the control group (RT-PCR-negative, n=52), the community cases group (RT-PCR-positive, n= 70) and the critically ill cases (ICU group; n=32). Genotyping of the studied polymorphisms was conducted by amplicon-based next-generation sequencing. The genotype distribution of the IFNAR2 rs2236757 was significantly different among the study groups (P = 0.001), while no significant differences were observed in the distribution of OAS3 rs10735079 genotypes (P = 0.091). Logistic regression analysis adjusted for possible confounding factors revealed a significant association between the risk allele rs2236757A and critical COVID-19 illness (P < 0.025). Among all patients, the rs2236757GA carriers were more likely to have sore throat (OR, 2.52 (95% CI 1.02-6.24); P = 0.011); the risk allele rs2236757A was associated with dyspnea (OR, 4.70 (95% CI 1.80-12.27); P < 0.001), while the rs10735079A carriers were less prone to develop muscle aches (OR, 0.34 (95% CI 0.13-0.88); P = 0.0248) and sore throat (OR, 0.17 (95% CI 0.05-0.55); P < 0.001). In conclusion, our results revealed that the rs2236757A variant was associated with critical COVID-19 illness and dyspnea, whereas the rs10735079A variant was protective for muscle aches and sore throat. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The author(s) received no specific funding for this work ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study procedure was approved by the research ethics committee at Al-Quds University (184/REC/2021), with implied consent from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files.