This study aimed to evaluate the role of genes encoding perforin (PRF1) and granzyme B (GZMB) in SARS-CoV-2 infection.

This is a cohort study in which the expression of the PRF1 and GZMB genes was quantified by qPCR, as well as the investigation of the rs35947132 and rs885822 polymorphisms in the PRF1 gene in 86 patients with COVID-19 treated in hospitals from Uberaba/MG, Brazil.

Patients who died had significantly lower PRF1 gene expression than those who survived. As for the severity of the disease, the expression was significantly lower of both genes in those patients with more severe clinical conditions. Characteristics such as sex, age and presence of comorbidities did not show differences in the expression of the PRF1 gene. Regarding the presence of polymorphisms, no differences were observed in relation to the parameters evaluated, such as outcome, severity, sex, age and presence of comorbidities, indicating that these alterations do not seem to directly influence these aspects. Despite this, it was observed that those who were homozygous for the rs885822 polymorphism had higher expression of the PRF1 gene when compared to patients with heterozygous or homozygous wild-type alleles.

The difference in the expression of the perforin gene regarding the outcome and severity may be due to greater activation of lymphocytes and consequently an increase in the expression of these genes, leading to a better prognosis. It is necessary to investigate whether patients who died and those who developed more severe manifestations of the disease have some immune deficiency related to cytotoxic lymphocytes. When it comes to the analysis of polymorphisms, the results found to differ from the literature, which considers that the presence of the rs35947132 polymorphism is more prevalent in patients with severe forms of COVID-19. The literature demonstrates that individuals with the polymorphic allele rs35947132 express less perforin, but the studies analyzed were performed using different techniques. A limitation of the present study is the sample size. We believe that the increase in the number of cases evaluated can provide us with a better understanding of this topic. Regarding the rs885822 polymorphism, the higher expression of the perforin gene contradicts the initial hypothesis of the work. However, one of the possible explanations for this fact would be the existence of other polymorphisms in linkage unbalance that trigger an increase in the expression of the PRF1 gene.

The present study concludes that the PRF1 gene was less expressed in patients with more severe COVID-19 and in those who died. Furthermore, in the analysis of perforin gene variants presence, no association was observed between the polymorphisms and the severity or outcome of individuals with COVID-19.