Impact of COVID-19 and vaccination on long-term survival in patients with solid malignancies: A nationwide cohort study

BACKGROUND: The long-term impact of SARS-CoV-2 infection and vaccination in patients with solid malignancies remains incompletely defined, particularly with respect to long-term oncologic outcomes and interactions with systemic anticancer therapies. METHODS: We conducted a nationwide, retrospective real-world cohort study using data from the Bulgarian Ministry of Health's United Information Portal. Adult patients (n = 1797) with solid malignancies who survived hospitalization for COVID-19 between March 2020 and June 2022 were included and followed through November 2025. Overall survival (OS) was evaluated according to vaccination status, vaccine platform (mRNA vs vector-based), primary tumor localization, and oncologic treatment modality. Multivariable logistic regression and propensity score matching were applied to adjust for demographic and clinical confounders. The study was conducted in accordance with ESMO-GROW guidelines. RESULTS: After a median follow-up of 48.6 months, mRNA-based vaccination was independently associated with lower long-term mortality (median OS, 43.6 months) compared with vector-based vaccination (34.9 months) or no vaccination (34.5 months) (OR, 0.41; 95% CI, 0.28-0.61; P < 0.0001). The survival benefit was most pronounced among patients receiving immune checkpoint inhibitors, particularly in lung cancer, where combined mRNA vaccination and immunotherapy was associated with superior outcomes (18.9% vs 31.1%; OR, 0.45; 95% CI, 0.20-0.98; P = 0.036). Results were consistent across multivariable and propensity score-matched analyses. CONCLUSIONS: In this large national real-world cohort with nearly five years of follow-up, mRNA-based COVID-19 vaccination was independently associated with improved long-term survival in patients with solid malignancies who survived COVID-19 hospitalization, supporting durable protective effects and suggesting a potential immunomodulatory interaction with immune checkpoint inhibition.