Active cancer in the era of COVID-19: A multivariable meta-analysis vs non-cancer controls with variant imputation.

Abstract

e23092 Background: Patients with active cancer are at increased risk from SARS-CoV-2 infection, yet the influence of recent cancer treatment, tumour subtype, and specific variants of concern (VOCs) remains unclear. We conducted a multivariable-adjusted meta-analysis to compare mortality and clinical severity between individuals with active cancer (diagnosed or treated within three years) and non-cancer controls, spanning pre- to post-Omicron periods. Methods: We searched Medline, Embase, Cochrane Central, and the WHO COVID-19 Research Database up to 25 November 2024 for eligible cohort studies enrolling ≥10 active cancer patients and reporting multivariable-adjusted SARS-CoV-2 outcomes against non-cancer comparators. We evaluated mortality (all-cause or COVID-19–specific) and severity (WHO ordinal scale) by tumor type, metastatic status, and dominant VOC, imputed via genomic data from NCBI GenBank and GISAID. Random-effects models generated pooled odds ratios (ORs) and 95% confidence intervals. Results: From 30 cohort studies (n = 281,270 with active cancer; n = 18.88 million controls), overall pooled analysis showed that active cancer significantly increased the odds of mortality (OR 1.70, 95% CI 1.36-2.12) and hospitalization (OR 1.58, 95% CI 1.22-2.06). Hematologic malignancies had higher ORs for mortality (2.10, 95% CI 1.43-3.07) than solid tumors (1.40, 95% CI 1.12-1.73), although the difference was not statistically significant ( p = 0.07). Thoracic and colorectal tumors, as well as metastatic disease, were associated with notably increased mortality risk. When stratified by VOC, Alpha (OR 4.59) and Omicron (OR 2.74) produced greater excess mortality in cancer patients compared to earlier SARS-CoV-2 lineages. Conclusions: Active malignancy elevates mortality and hospitalization relative to individuals without cancer, particularly among those with thoracic, colorectal, or metastatic disease. VOC-specific trends indicate greater vulnerability during Alpha and Omicron waves. These findings highlight the need for vigilant genomic surveillance and tailored clinical strategies to protect high-risk cancer populations against emerging future SARS-CoV-2 variants.