Comparative Effectiveness of Antivirals and Monoclonal Antibodies for Treating COVID‐19 Patients Infected With Omicron Variant: A Systematic Review and Network Meta‐Analysis

ABSTRACTAntiviral drugs likely remain effective against the SARS‐CoV‐2 Omicron variant, while monoclonal antibody (mAb) therapies have experienced drops in neutralizing ability. This systematic review and network meta‐analysis aims to estimate the comparative effectiveness of antivirals and mAb therapies for treating COVID‐19 patients infected with Omicron, capturing primarily acute outcomes. We searched multiple databases from July 4 to July 19, 2022, with updates through November 4, 2022. Studies comparing the effectiveness of antivirals or mAb to either nonuser controls or other treatments were included. Risk of bias was assessed using the Cochrane RoB 2 and ROBINS‐I tools. Data extraction and verification involved five independent researchers. Among 39 studies (727,893 individuals with COVID‐19, including 38 nonrandomized trials), nirmatrelvir/ritonavir and sotrovimab were associated with lower risks of mortality (HR = 0.317, 95% credible intervals [CrI] = 0.144–0.678; HR = 0.176, 95%CrI = 0.052–0.527) and hospitalization (HR = 0.479, 95%CrI = 0.319–0.711; HR = 0.489, 95%CrI = 0.293–0.797) compared with nonuser controls. Remdesivir users were associated with a lower risk of hospitalization (HR = 0.367, 95%CrI = 0.147–0.868) but not mortality. Molnupiravir and bebtelovimab showed no significant benefits for these outcomes. In conclusion, among individuals infected with COVID‐19 during the Omicron wave, mortality risk was lower with nirmatrelvir/ritonavir or sotrovimab use, whereas hospitalization was reduced with nirmatrelvir/ritonavir, remdesivir, or sotrovimab. Sotrovimab and nirmatrelvir/ritonavir were effective against Omicron B.1.1.529/BA.1 and BA.2/BA.4/BA.5 subvariants, respectively. A key limitation is that findings rely on data from the last search and may be impacted by potential changes in mortality risk due to immune evasion by emerging variants, highlighting the need for ongoing randomized trials across variants and populations.Trial RegistrationThe study was registered on PROSPERO, CRD42022351508.