DNA Salivary Methylation Levels of the ACE2 Promoter Are Not Related to ACE2 (rs2285666 and rs2074192), TMPRSS2 (rs12329760 and rs2070788) and ACE1 rs1799752 Polymorphisms in COVID-19 Survivors with Post-COVID-19 Condition.

Genetics and epigenetics are mechanisms proposed for explaining post-COVID-19 condition. This secondary analysis aimed to investigate if DNA methylation levels of the ACE2 promoter are different depending on the genotype of five COVID-19-related polymorphisms in individuals who had been previously hospitalized due to SARS-CoV-2 infection. We collected non-stimulated saliva samples from 279 (48.7% female, age: 56.0 ± 12.5 years) previously hospitalized COVID-19 survivors. The participants self-reported for the presence of post-COVID symptomatology that started after the infection and persisted at the time of the appointment. Three potential genotypes of ACE2 rs2285666 and rs2074192, TMPRSS2 rs12329760 and rs2070788, and ACE1 rs1799752 polymorphisms were identified from saliva samples. Further, methylation levels at five different locations (CpG) of dinucleotides in the ACE2 promoter were quantified using bisulfited pyrosequencing. Differences in the methylation percentage (%) of each CpG according to the genotype of the five polymorphisms were analyzed. Participants were evaluated up to 17.8 (SD: 5.2) months after hospital discharge. Eighty-eight percent (88.1%) of patients reported at least one post-COVID symptom (mean number of post-COVID symptoms: 3.0; SD: 1.9). Overall, we did not observe significant differences in the methylation levels of the ACE2 promoter according to the genotype of ACE2 rs2285666 and rs2074192, TMPRSS2 rs12329760 and rs2070788, or ACE1 rs1799752 single nucleoid polymorphisms. This study did not find an association between genetics (genotypes of five COVID-19-associated polymorphisms) and epigenetics (methylation levels of the ACE2 promoter) in a cohort of COVID-19 survivors with post-COVID-19 condition who were hospitalized during the first wave of the pandemic.