CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease
- Autori: Mastrorosa, I.; Cozzi-Lepri, A.; Matusali, G.; Colavita, F.; Lanini, S.; Rueca, M.; Oliva, A.; Berno, G.; Vergori, A.; Rosati, S.; Paulicelli, J.; Girardi, E.; Nicastri, E.; Maggi, F.; Antinori, A.; Mazzotta, V.; Null, N.; Al Moghazi, S.; Andreoni, M.; Bevilacqua, N.; Biliotti, E.; Blanc, P.; Bruno, R.; Caraffa, E.; Cascio, A.; Cattelan, A.M.; Cauda, R.; Carletti, F.; Cerva, C.; Corpolongo, A.; D'Abramo, A.; De Zottis, F.; Di Bari, S.; Di Perri, G.; Di Pietro, M.; Donno, D.R.; Faraglia, F.; Gavaruzzi, F.; Gentile, I.; Giancola, M.L.; Giombini, E.; Gori, A.; Grossi, P.; Gruber, C.E.M.; Iacobello, C.; Iaria, C.; Libanore, M.; Libertone, R.; Lichtner, M.; Loiacono, L.; Mariano, A.; Massari, M.; Mastroianni, C.M.; Meschi, S.; Milozzi, E.; Mussini, C.; Parrella, R.; Puoti, M.; Rizzardini, G.; Saracino, A.; Scorzolini, L.; Specchiarello, E.; Tavio, M.; Torti, C.; Viale, P.; Vita, S.; Vittozzi, P.
- Anno di pubblicazione: 2025
- Tipologia: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/696465
Abstract
Although in vitro studies suggest that neutralization by monoclonal antibodies (mAbs) against SARS CoV2 Omicron sub lineages is reduced, in vivo virological response data are lacking. MONET (EudraCT: 2021–004188-28) was multi-centric phase 4 open-label parallel randomized clinical trial, conducted in Italy over 2022–2023, to assess the efficacy of sotrovimab (SOT), tixagevimab/cilgavimab (TIX/CIL) and Nirmatrelvir/ritonavir (NMV/r), in outpatients at high risk for severe COVID-19. The outcome (secondary in the trial protocol) was SARS-CoV-2 variation in cycle threshold (CT) values over the first 7 days (D1-D7) of the trial. CT variation was compared by trial arms using unadjusted linear regression and after controlling for age. We included 346 individuals: 116 (34%) received SOT, 113 (33%) TIX/CIL, 117 (34%) NMV/r. Main characteristics were balanced across arms. Most of the participants were infected with BA.2 (52%) or BA.4/5 (35.5%). The data carried strong evidence that the mean CT change over D1-D7 was larger in subjects receiving NMV/r vs. the other arms (p < 0.001). We found no evidence that viral variant was an effect measure modifier for the contrasts of interest (p = 0.14). Our analysis provides strong evidence that NMV/r exerts a greater in vivo antiviral effect than anti-Spike mAbs against Omicron sub lineages, confirming previous in vitro data.