Nirmatrelvir plus ritonavir remains effective in vaccinated patients at risk of progression with COVID-19: A systematic review and meta-analysis.

Background: The efficacy of nirmatrelvir plus ritonavir (NMV-r) for vaccinated COVID-19 patients at high risk of progression is not adequately recognised. To address this gap, we conducted a systematic review and meta-analysis of current literature. Methods: We searched PubMed, Web of Science, Embase, Cochrane Library, and medRxiv for articles published up to 8 January 2023 on NMV-r in outpatients. At least two researchers screened articles, extracted data, and assessed the quality of selected studies. We evaluated the results via risk ratios (RRs) with 95% confidence intervals (CIs) and tested for heterogeneity using I2 statistics. Results: We included seven observational cohort studies comprising 224 238 vaccinated patients. According to our meta-analysis, NMV-r reduced 47% incidence of all-cause death or hospitalisation within 30 days for vaccinated patients (RR = 0.53; 95% CI = 0.40-0.70; I2 = 81%). After excluding the most influential result by sensitivity analysis, NMV-r still reduced risk of all-cause death or hospitalisation by 38% (RR = 0.62; 95% CI = 0.56-0.69; I2 = 0%). In our secondary outcome, NMV-r also showed its benefits in reducing all-cause death in vaccinated patients (RR = 0.40; 95% CI = 0.19-0.85; I2 = 23%). Conclusions: We found positive evidence for the use of NMV-r for vaccinated patients at high-risk of progression with mild to moderate COVID-19. However, large-scale RCTs are needed to confirm these findings. Registration: PROSPERO CRD42023391349.