Grant, AlyssaKabbani, DimaVuong, AndrewSkidmore, BeckyHsu, Amy T.Sanmugalingham, Geethade Vries, RienkLogan, SherrieGongal, PatriciaPiotrowski, Caroline C.Thavorn, Kednapa2026-02-032026-02-032026-01-29https://doi.org/10.1007/s41669-026-00639-whttp://hdl.handle.net/10393/51342Abstract Background High-risk populations, including transplant recipients, are at increased risk of severe Coronavirus disease 2019 (COVID-19) outcomes. Certain treatments and pre-exposure prophylaxis (PrEP) have been approved to reduce the risk of severe illness. However, data on the cost effectiveness of currently approved COVID-19 therapeutics and preventative treatments are limited for those at high-risk of severe disease. Objective The aim of this study was to systematically review the cost effectiveness of COVID-19 treatments and PrEP in high-risk, immunocompromised, and transplant populations. Methods Electronic databases were searched from inception to September 2025 for studies comparing costs and effectiveness of monoclonal antibodies PrEP or COVID-19 therapeutics in high-risk, immunocompromised or transplant populations. Two reviewers independently screened studies, extracted data, and critically appraised them using the Joanna Briggs Institute checklist for economic evaluations. Cost data are presented in 2025 US dollars. Results Of 8905 studies identified, 60 met inclusion criteria, with seven focused on or including transplant populations. Most studies were cost-utility analyses published between 2020 and 2025. Nirmatrelvir-ritonavir, tixagevimab-cilgavimab, casirivimab-imdevimab, sotrovimab, remdesivir, molnupiravir, and fluvoxamine were compared with no prophylaxis or standard of care. Among transplant populations, the incremental cost-effectiveness ratio (ICER) for tixagevimab-cilgavimab PrEP following vaccination was US$76,024 per quality-adjusted life year (QALY), while ICERs for COVID-19 therapeutics ranged from US$440 to US$126,676 per QALY. Conclusion Cost effectiveness varied widely across studies due to differences in variant periods, population risk profiles, model assumptions, and healthcare systems. Future research should integrate variant-specific effectiveness, real-world vaccine responsiveness, long-term COVID-19 outcomes, and adverse events to better inform resource allocation for transplant and other high-risk populations.Journal Article2026-02-03enThe Author(s)