CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease
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, co...
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-15641-1 |
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| author | Ilaria Mastrorosa Alessandro Cozzi-Lepri Giulia Matusali Francesca Colavita Simone Lanini Martina Rueca Alessandra Oliva Giulia Berno Alessandra Vergori Silvia Rosati Jessica Paulicelli Enrico Girardi Emanuele Nicastri Fabrizio Maggi Andrea Antinori Valentina Mazzotta the MONET Clinical Trial Group |
| author_facet | Ilaria Mastrorosa Alessandro Cozzi-Lepri Giulia Matusali Francesca Colavita Simone Lanini Martina Rueca Alessandra Oliva Giulia Berno Alessandra Vergori Silvia Rosati Jessica Paulicelli Enrico Girardi Emanuele Nicastri Fabrizio Maggi Andrea Antinori Valentina Mazzotta the MONET Clinical Trial Group |
| author_sort | Ilaria Mastrorosa |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-12e12a57ca1d42cb98e34f334a4b0ef3 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-12e12a57ca1d42cb98e34f334a4b0ef32025-08-24T11:22:44ZengNature PortfolioScientific Reports2045-23222025-08-011511810.1038/s41598-025-15641-1CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 diseaseIlaria Mastrorosa0Alessandro Cozzi-Lepri1Giulia Matusali2Francesca Colavita3Simone Lanini4Martina Rueca5Alessandra Oliva6Giulia Berno7Alessandra Vergori8Silvia Rosati9Jessica Paulicelli10Enrico Girardi11Emanuele Nicastri12Fabrizio Maggi13Andrea Antinori14Valentina Mazzotta15the MONET Clinical Trial GroupClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSCentre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health UCLLaboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinic Infectious Diseases, University of UdineLaboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSLaboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSScientific Direction, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSLaboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSClinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCSAbstract 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.https://doi.org/10.1038/s41598-025-15641-1SARS coronavirusRCTMonoclonal antibodiesAntiviral agentsCT valueAntibodies response |
| spellingShingle | Ilaria Mastrorosa Alessandro Cozzi-Lepri Giulia Matusali Francesca Colavita Simone Lanini Martina Rueca Alessandra Oliva Giulia Berno Alessandra Vergori Silvia Rosati Jessica Paulicelli Enrico Girardi Emanuele Nicastri Fabrizio Maggi Andrea Antinori Valentina Mazzotta the MONET Clinical Trial Group CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease Scientific Reports SARS coronavirus RCT Monoclonal antibodies Antiviral agents CT value Antibodies response |
| title | CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease |
| title_full | CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease |
| title_fullStr | CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease |
| title_full_unstemmed | CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease |
| title_short | CT changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe COVID19 disease |
| title_sort | ct changes in a randomized trial comparing early therapies in an outpatient population at high risk of severe covid19 disease |
| topic | SARS coronavirus RCT Monoclonal antibodies Antiviral agents CT value Antibodies response |
| url | https://doi.org/10.1038/s41598-025-15641-1 |
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