Coronavirus disease 2019 (COVID-19) is caused by a novel beta-coronavirus (SARS-CoV-2) and is characterized by a diverse clinical severity. The infection process of SARS-CoV-2 leads to a substantial increase in pro-inflammatory cytokines, contributing to damage of lung epithelial cells. Hereditary hemochromatosis (HH) is a disease characterized by excessive iron in the blood, and individuals with polymorphisms in the HFE gene (H63D, C282Y e S65C) have alterations in iron metabolism, which further exacerbate the inflammatory process. This study aims to investigate the association between HFE gene inheritance and the severity of the disease in patients with COVID-19.

Blood samples were collected from 87 adults diagnosed with COVID-19 and categorized based on disease severity, mild, moderate and severe. Molecular analysis was conducted to confirm the presence of mutations in the HFE gene (H63D, C282Y e S65C) using the PCR-RFLP method. Statistical analyses were performed using IBM SPSS Statistics 20 software, with a significance level set at 0.05. Associations between COVID-19 severity and biological sex were assessed using Fisher's exact test. The associations between homozygous wild-type, heterozygous, and homozygous mutant genotypes for each polymorphism were tested using the Chi-square test. To investigate the relationship between sex and HFE gene mutations with the severity of COVID-19, ANOVA was performed.

The group comprised 53 women (60.9%) and 34 men (39.1%) with ages ranging from 18 to 61 years, and a mean and standard deviation of 30.4 ±12.96. Among these, the majority of mild COVID-19 cases were observed in females (49.4%), while most moderate cases were found in males. Severe cases were exclusively identified in males, indicating a significant association between COVID-19 severity and gender (p < 0.05). A total of 522 alleles were evaluated for the HFE gene mutations. For the H63D mutation, were found 22 wild-type homozygous genotypes, 64 heterozygous and 1 mutant homozygous. For the C282Y, 78 wild-type homozygous, 7 heterozygous and 2 mutant homozygotes were found. For the S65C, 73 wild-type homozygous, 13 heterozygous and 1 mutant homozygous were found. Statistically significant differences were observed between genotypes for polymorphisms (p < 0.05). The covariate gender and the variables severity of the disease and presence or absence of HFE gene polymorphisms did not show significant differences. However, when comparing the severity of COVID with the H63D polymorphism, a statistically significant association was observed (p < 0.01).

The higher occurrence of moderate and severe COVID cases in males suggests a more severe disease course in this population group. The prevalence of the H63D mutation was more frequent in this group and associated with COVID-19 severity. The relatively low incidence of homozygous mutant alleles can be explained by the admixture of the Brazilian population. The C282Y and S65C genotypes exhibit low expressiveness, which is insufficient to establish a significant relationship.

The H63D genotype exhibits a higher frequency of heterozygotes and is associated with increased clinical severity of COVID-19, especially in males. Further investigations are warranted to characterize the HFE gene and develop strategies for managing exacerbated COVID-19 symptoms.