CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease

• Published in: Scientific reports Vol. 15; no. 1; pp. 30244 - 8
• Main Authors: Mastrorosa, Ilaria, Cozzi-Lepri, Alessandro, Matusali, Giulia, Colavita, Francesca, Lanini, Simone, Rueca, Martina, Oliva, Alessandra, Berno, Giulia, Vergori, Alessandra, Rosati, Silvia, Paulicelli, Jessica, Girardi, Enrico, Nicastri, Emanuele, Maggi, Fabrizio, Antinori, Andrea, Mazzotta, Valentina
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.08.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 692/308; 692/53; 692/700; Antibodies response; Antiviral agents; Body mass index; Chronic obstructive pulmonary disease; Clinical trials; COVID-19; COVID-19 vaccines; CT value; Humanities and Social Sciences; Immunization; Monoclonal antibodies; multidisciplinary; Neutralization; RCT; Ritonavir; SARS coronavirus; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Antiviral agents; RCT; CT value; SARS coronavirus; Monoclonal antibodies; Inflammatory markers; Antibodies response
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-15641-1

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.