Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern

• Published in: eLife 2022-11, Vol.11
• Main Authors: Mazzaferri, Fulvia, Mirandola, Massimo, Savoldi, Alessia, De Nardo, Pasquale, Morra, Matteo, Tebon, Maela, Armellini, Maddalena, De Luca, Giulia, Calandrino, Lucrezia, Sasset, Lolita, D'Elia, Denise, Sozio, Emanuela, Danese, Elisa, Gibellini, Davide, Monne, Isabella, Scroccaro, Giovanna, Magrini, Nicola, Cattelan, Annamaria, Tascini, Carlo, Tacconelli, Evelina
• Format: Article
• Language: English
• Subjects: Automation; bamlanivimab/etesevimab; Cardiovascular disease; casirivimab/imdevimab; Coronaviruses; COVID-19; COVID-19 vaccines; Diabetes; early covid-19; Emergency medical care; Hospitalization; Immunization; Immunotherapy; Kidney diseases; Medicine; Monoclonal antibodies; monoclonal antibody; Mortality; Omicron; Oxygen therapy; Patients; Proteins; Serology; Severe acute respiratory syndrome coronavirus 2; sotrovimab
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.79639

Background:Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies according to the variant of concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC.Methods:The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of early treatments with bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with mild-to-moderate SARS-CoV-2 infection. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was coronavirus disease 2019 (COVID-19) progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions.Results:Overall, 319 patients were included. Among 141 patients infected with Delta, no COVID-19 progression was recorded, and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.90). Among 170 patients infected with Omicron (80.6% BA.1 and 19.4% BA.1.1), two COVID-19 progressions were recorded, both in the bamlanivimab/etesevimab group, and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared with the bamlanivimab/etesevimab and casirivimab/imdevimab groups (HR 0.53 and HR 0.45, 95% CI 0.36–0.77 and 95% CI 0.30–0.67, p