The COVID-19 pandemic has reshaped the landscape of global health, revealing novel interactions between infectious diseases and chronic conditions such as cancer. Beyond acute infection, growing evidence suggests that persistent exposure to SARS-CoV-2 spike protein, whether through infection or vaccination, may sustain inflammatory pathways that contribute to tumour progression and immune modulation. This review explores the overlap between post-COVID inflammation, particularly in Long-COVID syndromes and the tumour microenvironment (TME), focusing on key mediators such as IL-6, TNF-α, IL-1β, and NF-κB. We revisit the concept of the cytokine storm in the context of persistent inflammation, spike protein immunogenicity and immune exhaustion, proposing a model in which chronic inflammatory signalling may disrupt tumour immune surveillance, reawaken dormant cancer cells and compromise the efficacy of immunotherapies. Comparative analysis with other cancer types highlights shared pathways of oncogenic inflammation. Lastly, we outline emerging therapeutic strategies to mitigate these effects, including cytokine-targeted interventions and immunomodulatory screening in post-COVID cancer patients. These post-pandemic insights call for urgent translational research to ensure effective and safe cancer immunotherapy in the evolving inflammatory landscape.
