SARS-CoV-2 Infection and Vaccination, Immune Dysregulation, and Cancer

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits highly heterogeneous immune responses that influence both acute disease severity and long-term immunological outcomes. While effective antiviral immunity leads to viral clearance in many individuals, a subset develops persistent immune dysregulation characterized by chronic inflammation, immune exhaustion, and impaired tissue repair, hallmarks of long COVID. These immune alterations are parallel to established mechanisms of carcinogenesis and tumor progression, including sustained cytokine signaling, oxidative stress, metabolic reprogramming, and disruption of antitumor immune surveillance. Emerging evidence suggests that SARS-CoV-2 may further interact with cancer biology through direct or abortive infection of tumor or stromal cells, as well as through viral protein–mediated activation of oncogenic and inflammatory signaling pathways such as NF-κB, MAPK/ERK, JAK/STAT3, and Toll-like receptor signaling. In addition, immune evasion strategies observed in both chronic viral infection and cancer, including immune checkpoint upregulation, impaired antigen presentation, and the establishment of immunosuppressive microenvironments, may be reinforced following SARS-CoV-2 infection. SARS-CoV-2 vaccination limits severe disease and persistent immune activation, thereby potentially mitigating long-term tumor-permissive immune states without evidence of oncogenic risk. These observations position SARS-CoV-2 infection as a non-classical but biologically relevant modifier of cancer-associated immune landscapes. Elucidating the long-term consequences of post-infectious immune remodeling will be essential for defining cancer risk, optimizing surveillance strategies, and informing therapeutic interventions in COVID-19 survivors.