Lin, Shen-HuaShen-HuaLinLiu, Jen-WeiJen-WeiLiuYen, Yi-TiYi-TiYenChen, Mong-TanMong-TanChenJANN-TAY WANGYU-KANG TUCHI-TAI FANGSHAN-CHWEN CHANG2025-05-162025-05-162025-03-28https://scholars.lib.ntu.edu.tw/handle/123456789/729370Background: The efficacy of molnupiravir for COVID-19 treatment remains controversial due to substantial heterogeneity in dosage and study settings across randomised controlled trials (RCTs). Method: We systematically searched Medline, PubMed, Embase, and the Cochrane Register of Clinical Trials up to February 3, 2025, for RCTs and real-world studies evaluating molnupiravir 800 mg twice daily as an early treatment for COVID-19 to prevent mortality and hospitalisation in high-risk adult outpatients. The primary outcomes were all-cause mortality and all-cause hospitalisation. Random-effects models were used to estimate pooled effect sizes. Results: Thirty-four studies were included, comprising 30,345 participants from 11 RCTs and 1,581,737 participants from 23 cohort studies. Molnupiravir reduced mortality risk by 55 %–65 % at 28 days (RCTs: risk ratio [RR] 0.35; 95 % CI 0.12–0.98, I2 0 %; cohort studies: RR 0.45; 95 % CI 0.27–0.73, I2 91 %). This benefit persisted at 3 months (RR 0.47; 95 % CI 0.23–0.95, I2 93 %) and 6 months (RR 0.62; 95 % CI 0.52–0.74, I2 0 %). The effectiveness in preventing 28-day hospitalisation varied by participants’ mean age in both RCTs (35–45 vs. 45–57 years: RR 0.55; 95 % CI 0.36–0.84 vs. 1.06; 95 % CI 0.81–1.39, subgroup difference P = 0.01) and cohort studies (62–74 vs. 75–85 years: RR 0.88; 95 % CI 0.77–1.01 vs. 0.56; 95 % CI 0.44–0.72, subgroup difference P < 0.01). Conclusions: Molnupiravir significantly reduces the risk of mortality. It also lowers the risk of hospitalisation in the oldest group (mean age ≥75 years) but not in younger groups (mean age 45–74 years).enCOVID-19HospitalisationMeta-analysisMolnupiravirMortality[SDGs]SDG3journal article10.1016/j.jmii.2025.03.01540204602