Male Sex as a Predictor of Worse Prognosis and Clinical Evolution in Patients with Cancer and SARS-CoV-2 Infection, Independent of the rs41386349 PDCD1 Polymorphism

COVID-19 continues to spread six years after its discovery. Cancer patients are at an increased risk of severe outcomes, likely due to immunosuppression and tumor-related dysregulation. Programmed cell death protein 1 (PD-1), encoded by the PDCD1 gene, is a critical immune checkpoint involved in T-cell regulation. Since genetic polymorphisms can influence immune responses and individual susceptibility to SARS-CoV-2 infection, this case–control study aimed to investigate the association between the PDCD1 rs41386349 polymorphism and COVID-19 severity in individuals with and without cancer. This study included 279 COVID-19-positive and 160 negative individuals, genotyped by qPCR. COVID-19- positive cancer patients were significantly more likely to develop moderate (OR = 13.6) and severe (OR > 200) disease compared to cancer-negative individuals. No association was observed between the PDCD1 polymorphism and SARS-CoV-2 infection or disease severity, even after adjusting for cancer status, age and sex. However, age and sex were independently associated with severe outcomes: each additional year of age increased the odds of severe disease by 5.3%, and male patients had a three times higher risk of severe COVID-19. These findings confirm that cancer, male sex and older age are major predictors of worse prognosis in COVID-19, while the rs41386349 polymorphism alone does not appear to influence susceptibility or disease progression.