SARS-COV-2 nasopharyngeal viral load change in a multicenter randomized
clinical trial comparing early therapies for COVID-19 in
non-hospitalized adults with high risk of severe COVID-19 (the MONET
TRIAL)
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 mAbs
against Omicron sublineages, confirming previous in vitro data.