Therefore, this study conducted a detailed analysis to investigate the association between genes and the second signal for T cell activation and understand the effect of genes on the side effects after vaccination, including cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily member 4 (TNFSF4), and programmed cell death protein 1 (PDCD1) and the side effects caused by COVID-19 vaccination. The gene discussed is PDCD1; the disease is COVID-19.