. 2025 May;97(5):e70379.
doi: 10.1002/jmv.70379. Comparative Analysis of Early COVID-19 Treatment Efficacy in a Multicentric Regional Cohort in Italy: Emulation of a Series of Target Trials
Valentina Mazzotta 1 , Alessandro Cozzi Lepri 2 , Cosmo Del Borgo 3 , Simone Lanini 4 , Silvia Meschi 5 , Silvia Garattini 3 , Silvia Rosati 1 , Valentina Siciliano 6 , Alessandra Vergori 1 7 , Luigi Coppola 8 , Antonio Falletta 9 , Anna Carraro 3 , Giulia Gramigna 5 , Alessandra Oliva 1 , Elena Matteini 6 , Andrea Gasperin 3 , Giuseppina Giannico 1 , Ilaria Mastrorosa 1 , Giulia Matusali 5 , Alessandra D'Abramo 1 , Raffaella Marocco 3 , Eugenia Milozzi 1 , Carlotta Cerva 1 , Francesca Gavaruzzi 1 , Martina Rueca 5 , Claudia Cimaglia 10 , Pierluca Piselli 10 , Massimo Fantoni 11 , Enrico Girardi 12 , Loredana Sarmati 8 , Claudio M Mastroianni 9 , Massimo Andreoni 8 , Carlo Torti 6 11 , Emanuele Nicastri 1 , Fabrizio Maggi 5 , Miriam Lichtner 3 , Andrea Antinori 1 ; Early Treatment for COVID‐19 Lazio Study Group
Affiliations
- PMID: 40326978
- PMCID: PMC12054396
- DOI: 10.1002/jmv.70379
Studies comparing all available strategies for the early treatment of mild-to-moderate COVID-19 during the Omicron era are lacking. We included people with mild-to-moderate COVID-19 and at high risk of progressing to severe disease attending five outpatient clinics in Italy over 2022-2023. The primary outcome was the proportion of participants who experienced Day-30 hospitalization due to COVID-19 or death. Participants received either nirmatrelvir/ritonavir (NMV/r), molnupiravir (MLP), remdesivir (RDV), sotrovimab (SOT), or tixagevimab/cilgavimab (TIX/CIL). We included 10 038 individuals: females 5052 (50%), median age 71 years (IQR 59-81). In total, 1919 (19%) received SOT, 3732 (37.2%) MLP, 1444 (14%) RDV, 2510 (25%) NMV/r, and 433 (4%) TIX/CIL. Only 1689 (17%) had incomplete vaccination, and 2435 (24.3%) were not immunocompetent. The rate of hospitalization/death was 2.40% (95% CI 2.10-2.71). Unadjusted rates were 0.88% (95% CI 0.55-1.32) for NMV/r, 1.69% (95% CI 1.30-2.15) for MLP, 3.0% (95% CI 1.61-5.08) for TIX/CIL, 3.54% (95% CI 2.76-4.47) for SOT and 5.12% (95% CI 4.05-6.39) for RDV. Weighted analysis showed that NMV/r and MLP were superior to all other interventions. In our population of individuals at high risk of progression to severe disease, there was clinical benefit in using NMV/r or MLP instead of mAbs-based therapies or RDV.
Keywords: SARS coronavirus; antiviral agents; epidemiology; virus classification.