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

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.