Influence of Disease Severity and Gender on HLA-C Methylation in COVID-19 Patients

In the pathophysiology of COVID-19, immunomodulatory factors play a vital role. Viruses have epigenetic effects on various genes, particularly methylation. Explaining the changes in immunological factor methylation levels during viral infections requires substantial consideration. HLA-C is a crucial determinant of immune function and NK cell activity and is primarily implicated in viral infections. This research focused on studying HLA-C methylation in COVID-19 patients with different severity. Peripheral blood samples were collected from 470 patients (235 men and 235 women) with RT-qPCR-confirmed COVID-19 test and classified into moderate, severe, and critical groups based on WHO criteria. Also, one hundred (50 men and 50 women) healthy subjects were selected as the control group. Peripheral blood mononuclear cells were used for DNA extraction, and the methylation-specific PCR (MSP) method and gel electrophoresis were used to determine the methylation status of the HLA-C. Significant statistical differences in HLA-C methylation were observed among cases and controls and various stages of the disease. HLA-C methylation in men and women has decreased in all stages (p < 0.05). In comparison with control, HLA-C methylation in both genders were as follows: moderate (women: 41.0%, men: 52.33%), severe (women: 43.42%, men: 64.86%), critical (women: 42.33%, men: 60.07%), and total patients (women: 45.52%, men: 56.97%). Furthermore, the methylation levels in men were higher than in women in all groups (p < 0.05). Significantly, among all groups, the severe group of men participants showed the highest methylation percentage (p < 0.05). No significant differences were detected for different disease severity in the women group (p > 0.1). This study found that HLA-C methylation was significantly lower in COVID-19 patients with different disease severity. There were also significant differences in HLA-C methylation between men and women patients with different severity. Therefore, during managing viral infections, particularly COVID-19, it is critical to consider patient gender and disease severity.