The association of , , , and polymorphisms with COVID-19 severity: A systematic review and meta-analysis.

Genes involved in the regulation of viral recognition and its entry into a host cell have been identified as candidates for genetic association studies on COVID-19 severity. Published findings on the effects of polymorphisms within , , , and genes remained inconclusive, so we conducted a systematic review and meta-analysis in order to elucidate their potential involvement in the genetic basis underlying the severity of COVID-19 and/or an outcome of SARS-CoV-2 infection. Identification of potentially eligible studies was based on PubMed, Scopus and Web of Science database search. Relevant studies (n=29) with a total number of 8247 SARS-CoV-2-positive participants were included in qualitative synthesis, while results of 21 studies involving 5939 were pooled in meta-analysis. Minor allele I of rs1799752 located within was identified as a protective variant against severe COVID-19, while its effect on mortality rate was opposite. Similarly, minor allele A of polymorphism, rs2285666, was found to associate with a decreased risk of severe COVID-19 ( = 0.003, OR = 0.512, 95 % CI = 0.331-0.793). Statistical significance was also seen for the association between COVID-19 severity and rs12329760 located within . Our results did not support the supposed association of rs12252 in and polymorphisms within with disease severity. We conclude that genetic variants within , and may be potential biomarkers of COVID-19 severity, which needs to be further confirmed in a larger set of studies.