tetano
Editor, Senior Moderator
Sci Rep
. 2025 Aug 18;15(1):30244.
doi: 10.1038/s41598-025-15641-1. CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease
Ilaria Mastrorosa[SUP] 1 [/SUP], Alessandro Cozzi-Lepri[SUP] 2 [/SUP], Giulia Matusali[SUP] 3 [/SUP], Francesca Colavita[SUP] 1 3 [/SUP], Simone Lanini[SUP] 4 [/SUP], Martina Rueca[SUP] 3 [/SUP], Alessandra Oliva[SUP] 1 [/SUP], Giulia Berno[SUP] 3 [/SUP], Alessandra Vergori[SUP] 1 [/SUP], Silvia Rosati[SUP] 1 [/SUP], Jessica Paulicelli[SUP] 1 [/SUP], Enrico Girardi[SUP] 5 [/SUP], Emanuele Nicastri[SUP] 1 [/SUP], Fabrizio Maggi[SUP] 3 [/SUP], Andrea Antinori[SUP] 1 [/SUP], Valentina Mazzotta[SUP] 1 [/SUP]; MONET Clinical Trial Group
Collaborators, Affiliations
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.
Keywords: Antibodies response; Antiviral agents; CT value; Inflammatory markers; Monoclonal antibodies; RCT; SARS coronavirus.
. 2025 Aug 18;15(1):30244.
doi: 10.1038/s41598-025-15641-1. CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease
Ilaria Mastrorosa[SUP] 1 [/SUP], Alessandro Cozzi-Lepri[SUP] 2 [/SUP], Giulia Matusali[SUP] 3 [/SUP], Francesca Colavita[SUP] 1 3 [/SUP], Simone Lanini[SUP] 4 [/SUP], Martina Rueca[SUP] 3 [/SUP], Alessandra Oliva[SUP] 1 [/SUP], Giulia Berno[SUP] 3 [/SUP], Alessandra Vergori[SUP] 1 [/SUP], Silvia Rosati[SUP] 1 [/SUP], Jessica Paulicelli[SUP] 1 [/SUP], Enrico Girardi[SUP] 5 [/SUP], Emanuele Nicastri[SUP] 1 [/SUP], Fabrizio Maggi[SUP] 3 [/SUP], Andrea Antinori[SUP] 1 [/SUP], Valentina Mazzotta[SUP] 1 [/SUP]; MONET Clinical Trial Group
Collaborators, Affiliations
- PMID: 40825809
- 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.
Keywords: Antibodies response; Antiviral agents; CT value; Inflammatory markers; Monoclonal antibodies; RCT; SARS coronavirus.