The clinical effectiveness of REGEN-COV in SARS-CoV-2 infection with Omicron versus Delta variants

Abstract

Background In vitro studies suggesting that REGEN-COV (casirivimab plus imdevimab monoclonal antibodies) had poor efficacy against Omicron-variant SARS-CoV-2 infection led to amendment of REGEN-COV’s Emergency Use Authorization to recommend use only in regions without high Omicron prevalence. REGEN-COV’s relative clinical effectiveness for Omicron is unknown. Methods and findings We conducted a retrospective cohort study of non-hospitalized adults who tested positive for SARS-CoV-2 by polymerase chain reaction at the University of Miami Health System from July 19 –November 21, 2021 (Delta period) and December 6, 2021 –January 7, 2022 (Omicron period). Subjects were stratified be REGEN-COV receipt within 72h of test positivity and by time period of infection. We constructed multivariable logistic regression models to assess the differential association of REGEN-COV receipt with hospitalization within 30 days (primary outcome) and ED presentation; all models included three exposure terms (REGEN-COV receipt, Omicron vs Delta period, interaction of REGEN-COV with time period) and potential confounders (vaccination status, vaccine boosting, cancer diagnosis). Our cohort consisted of 2,083 adults in the Delta period (213 [10.2%] received REGEN-COV) and 4,201 in the Omicron period (156 [3.7%] received REGEN-COV). Hospitalization was less common during the Omicron period than during Delta (0.9% vs 1.7%, p = 0.78) and more common for patients receiving REGEN-COV than not (5.7% vs 0.9%, p<0.001). After adjustment, we found no differential association of REGEN-COV use during Omicron vs Delta with hospitalization within 30d (adjusted odds ratio [95% confidence interval] for the interaction term: 2.31 [0.76–6.92], p = 0.13). Similarly, we found no differential association for hospitalization within 15d (2.45 [0.63–9.59], p = 0.20) or emergency department presentation within 30d (1.43 [0.57–3.51], p = 0.40) or within 15d (1.79 [0.65–4.82], p = 0.30). Conclusions Within the limitations of this study’s power to detect a difference, we identified no differential effectiveness of REGEN-COV in the context of Omicron vs Delta SARS-CoV-2 infection.