TAS2R38 gene methylation is associated with syndrome Coronavirus 2 (SARS-CoV-2) infection and clinical symptoms.

TAS2R38 is the T2R receptor primarily associated with the innate immune response of the respiratory system. It activates a response mediated by nitric oxide (NO), which has been shown to inhibit the replication of SARS-CoV-2. TAS2R38 polymorphisms (SNPs) that decrease receptor functionality contributing to individual differences in susceptibility to airway infections. DNA methylation (DNAm) may affect gene expression influencing disease development, including COVID-19. We analyzed the effect of SARS-CoV-2 on the methylation pattern of TAS2R38 (at cg25481253, a CpG site located in the coding region) during infection and after the cessation of the exposure to the virus, also considering the disease severity and TAS2R38 SNPs. Our results showed a positive relationship between TAS2R38 DNAm levels and disease severity in the COVID-19 patients and a return to a normal state after the infection. In addition, our results showed an association between DNAm level and the TAS2R38 genotype in participants who recovered from the disease. PAV/PAV genotypes showed lower TAS2R38 DNAm levels than heterozygous and AVI homozygous. In conclusion, our results clearly indicate the involvement of TAS2R38 DNAm alteration in COVID-19 severity and suggest a role of the methylation changes at cg25481253 in the regulation of the TAS2R38 expression.