Recent evidence has linked the interferon-induced transmembrane protein 3 gene (IFITM3) to coronavirus disease 2019 (COVID-19) outcomes, but the results are inconsistent. The purpose of this meta-analysis was to evaluate the association of IFITM3 gene polymorphisms with COVID-19 susceptibility and severity.

A systematic search was performed with PubMed, Web of Science, Cochrane Library, and Embase from the date of inception to 20 December 2021. The results were analyzed with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). The robustness was performed using the method of sequential removal for each trial.

Four studies involving 1989 subjects were included, from which 1114 patients were positive for COVID-19. For IFITM3 rs12252, the pooled OR showed that there was a significant association between the genotype frequencies and infection with COVID-19 in any of the gene models, i.e., the allelic model (OR = 1.91, 95% CI, 1.36–2.68), the dominant model (OR = 1.80, 95% CI, 1.27–2.56), the recessive model (OR = 5.67, 95% CI, 1.01–31.77), the heterozygous model (OR = 1.65, 95% CI, 1.16–2.36) and the homozygous model (OR = 5.88, 95% CI, 1.05–32.98). The results stratified by severity showed that there was a significant correlation only between the allelic (OR = 0.69, 95% CI, 0.49–0.97) and recessive (OR = 0.43, 95% CI, 0.20–0.93) models. Our results did not support the associations between the IFITM3 rs34481144 gene polymorphism and COVID-19 susceptibility or severity in any of the gene models.

The findings indicated that IFITM3 rs12252 gene polymorphisms were associated with COVID-19 susceptibility and that the rs12252-C variant was particularly critical for severity. Genetic factors should be considered in future vaccine development.