Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.01.29.22270090; this version posted January 31, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. 1 Doubtful Clinical Benefit of Casirivimab-Imdevimab Treatment for Disease Severity Outcome of High-Risk Patients with SARS-CoV-2 Delta Variant Infection Noah Shopen 1,5*, Michal Dekel2,5*, Michal Mizrahi1,5, Efrat Zandberg1,5, Nancy Bishouty4,5, Daniel Talmud1,5, Ben Vaknin1,5, Shira Haberman5, Malka Katz Shalhav1,5, David Zeltser1,5, Neta Cohen1,3,5 *Equal contribution 1 Emergency Department, 2Division of Infectious Disease, 3Pediatric Emergency Department, Dana Dwek Children Hospital, 4Clinical Pharmacy Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, affiliated to the 5Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Corresponding author: Neta Cohen, MD, Emergency Department, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv, 6423906 Israel. E-mail: netarab81@gmail.com. ORCID ID: 0000-0001-7694-6407. Key words: Casirivimab/Imdevimab therapy, SARS-CoV-2 Delta Variant, High-Risk Patients, Severe outcome, BNT162b2 vaccine. Statements and Declarations Funding: None. Conflict of interest statement: The authors have no conflict of interests to disclose. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2022.01.29.22270090; this version posted January 31, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. 2 ABSTRACT Casirivimab/Imdevimab therapy reportedly retains neutralization potency against circulating SARS-CoV-2 variants, including Delta (B.1.617.2), but there are sparse data on its clinical benefit against the Delta variant among vaccinated and unvaccinated patients. We explored its therapeutic effect on COVID-19 severity outcome in terms of room air saturation <93% within 14 days of initial presentation and 45-day all-cause mortality among high-risk patients with SARS-CoV-2 Delta variant infection and compared its effect between vaccinated and unvaccinated patients. We conducted a retrospective cohort study at a tertiary care medical center between 6/2021 and 9/2021 and included patients who presented with a positive PCR for SARS-CoV-2 and fulfilled the criteria for Casirivimab/Imdevimab treatment. Of the 359 suitable patients (52% female, median age 63 years), 116 were treated with Casirivimab/Imdevimab and 243 were not. Two-hundred and one (56%) patients had received at least 2 SARS-CoV-2 vaccinations. Casirivimab/Imdevimab treatment was not an independent protective factor of COVID19 severity outcome (multivariable analysis). Chronic kidney disease (aOR=3.51 [95%CI: 1.34-9.20], P=0.01), lower saturation levels (aOR=0.7 [95%CI: 0.58–0.85], P<0.01), abnormal chest x-ray findings (aOR=2.92, [95%CI: 1.24–6.87, P=0.01), and higher C-reactive protein levels (aOR=1.01 [95%CI: 1.00–1.01], P=0.008) were independent risk factors of COVID-19 severity. Positive immunization status was an independent protective factor (aOR=0.33 [95%CI: 0.14–0.77],..