Evaluation of nirmatrelvir/ritonavir treatment for COVID-19 on health-related outcomes: a global economic value systematic literature review

Aims Nirmatrelvir/ritonavir (NMV/r)Footnotei is an antiviral drug indicated for the treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk of progressing to severe disease. We performed an updated economic systematic literature review (eSLR) of NMV/r to build upon evidence reported in our previous eSLR and additionally examine the health-related outcomes associated with NMV/r and any potential effect of long COVID.Methods A systematic search of Embase, PubMed, Cochrane, and EconLit and of conference and health technology assessment agency websites was performed to identify economic analyses published between January 2022 and October 2025.Results Of the 33 included economic evaluations, most were cost-utility analyses (n = 16) and used an analysis of a short-term decision tree with a long-term Markov model (n = 11). Several types of health-related endpoints were reported by studies, with most including hospital-related endpoints (n = 20), quality-adjusted life-years (QALYs) (n = 18), and death-related endpoints (n = 18). Positive health-related outcomes were associated with NMV/r treatment, including reductions in hospitalizations and deaths and an increase in QALYs. NMV/r treatment was also associated with a reduced number of patients with long COVID complications.Limitations Most studies were conducted in high-income countries, were based on different COVID-19 variants, and were limited in data on the long COVID population.Conclusion In addition to monetary benefits, NMV/r provides short-term and long-term health-related benefits to patients with mild to moderate COVID-19. This study provides further support for NMV/r as a cost-effective treatment option.