COVID-19 infection may induce persistent pulmonary sequelae, potentially elevating perioperative risks in non-small cell lung cancer (NSCLC) patients. This study aims to evaluate the impact of prior COVID-19 infection on perioperative outcomes in NSCLC patients undergoing lung resection.

This prospective observational cohort study enrolled NSCLC patients undergoing surgery at Shanghai Chest Hospital (May 2024-January 2025). Patients were stratified into COVID-19-exposed (PCOV) and non-exposed (NCOV) cohorts. The primary endpoint: 30-day postoperative pulmonary complications (PPCs); secondary endpoints: surgical duration and postoperative hospital stay. Propensity-score matching (PSM; 1:1 ratio) was performed to address confounders.

Among 2285 enrolled patients (NCOV: 913; PCOV: 1372), PSM yielded 762 matched pairs with balanced baseline characteristics. The PCOV group exhibited significantly higher 30-day PPC rates (Unmatched: 18.0% vs. 10.4%, P < 0.001; Matched: 17.3% vs. 10.8%, P < 0.001), prolonged surgical durations (Unmatched: 108.6[86.0–128.2] vs. 123.6[93.7–139.0], P < 0.001; Matched: 111.8[87.4–129.1] vs. 121.1[92.8–138.2], P < 0.001; mins, median[interquartile range(IQR)]) and extended postoperative hospital stays (Unmatched: 4[4–5] vs. 5[4–6], P < 0.001; Matched: 4[4–5] vs. 5[4–6], P < 0.001; days, median[IQR]) compared to the NCOV group. Other perioperative outcomes were comparable between the groups. Stratified analyses demonstrated elevated 30-day PPC risk in all predefined PCOV subgroups except patients aged ≤ 65 years (Unmatched: 1.312[0.919–1.873], P = 0.135; Matched: 1.302[0.846–2.004], P = 0.230; odds ratio [95% confidence interval]). Further analysis for patients aged ≤ 65 years showed that the PCOV group exhibited no significant differences in perioperative outcomes compared to the NCOV group, except for surgical duration.

Prior COVID-19 infection is associated with increased PPCs, longer operative times, and delayed discharge in NSCLC patients. However, perioperative outcomes remained comparable in patients ≤ 65 years, suggesting age-dependent resilience to COVID-19-related surgical risks.