Doubtful Clinical Benefit of Casirivimab-Imdevimab Treatment for Disease Severity Outcome of High-Risk Patients with SARS-CoV-2 Delta Variant Infection

Noah Shopen; Michal Dekel; Michal Mizrahi; Efrat Zandberg; Nancy Bishouty; Daniel Talmud; Ben Vaknin; Shira Haberman; Malka Katz Shalhav; David Zeltser; Neta Cohen

Noah Shopen, Michal Dekel, Michal Mizrahi, Efrat Zandberg, Nancy Bishouty, Daniel Talmud, Ben Vaknin, Shira Haberman, Malka Katz Shalhav, David Zeltser, MD Neta Cohen

doi:10.1101/2022.01.29.22270090

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 COVID-19 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], P=0.01). A sub analysis of patients treated with Casirivimab/Imdevimab revealed no significant difference in COVID-19 severity between vaccinated and unvaccinated patients. These findings demonstrate no added benefit of Casrivimab/Imdevinab treatment for high-risk patients with the SARS-CoV-2 Delta variant infection, regardless of their vaccination status.

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DOI record: { "DOI": "10.1101/2022.01.29.22270090", "URL": "http://dx.doi.org/10.1101/2022.01.29.22270090", "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 COVID 19 severity outcome (multivariable analysis). Chronic kidney disease (aOR=3.51 [95%CI: 1.34 to 9.20], P=0.01), lower saturation levels (aOR=0.7 [95%CI: 0.58 to 0.85], P<0.01), abnormal chest x ray findings (aOR=2.92, [95%CI: 1.24 to 6.87, P=0.01), and higher C-reactive protein levels (aOR=1.01 [95%CI: 1.00 to 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 to 0.77], P=0.01). A sub analysis of patients treated with Casirivimab/Imdevimab revealed no significant difference in COVID-19 severity between vaccinated and unvaccinated patients. These findings demonstrate no added benefit of Casrivimab/Imdevinab treatment for high-risk patients with the SARS-CoV-2 Delta variant infection, regardless of their vaccination status.", "accepted": { "date-parts": [ [ 2022, 1, 31 ] ] }, "author": [ { "affiliation": [], "family": "Shopen", "given": "Noah", "sequence": "first" }, { "affiliation": [], "family": "Dekel", "given": "Michal", "sequence": "additional" }, { "affiliation": [], "family": "Mizrahi", "given": "Michal", "sequence": "additional" }, { "affiliation": [], "family": "Zandberg", "given": "Efrat", "sequence": "additional" }, { "affiliation": [], "family": "Bishouty", "given": "Nancy", "sequence": "additional" }, { "affiliation": [], "family": "Talmud", "given": "Daniel", "sequence": "additional" }, { "affiliation": [], "family": "Vaknin", "given": "Ben", "sequence": "additional" }, { "affiliation": [], "family": "Haberman", "given": "Shira", "sequence": "additional" }, { "affiliation": [], "family": "Katz Shalhav", "given": "Malka", "sequence": "additional" }, { "affiliation": [], "family": "Zeltser", "given": "David", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-7694-6407", "affiliation": [], "authenticated-orcid": false, "family": "Cohen", "given": "Neta", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2022, 1, 31 ] ], "date-time": "2022-01-31T21:10:26Z", "timestamp": 1643663426000 }, "deposited": { "date-parts": [ [ 2022, 1, 31 ] ], "date-time": "2022-01-31T21:10:26Z", "timestamp": 1643663426000 }, "group-title": "Emergency Medicine", "indexed": { "date-parts": [ [ 2022, 1, 31 ] ], "date-time": "2022-01-31T21:41:28Z", "timestamp": 1643665288563 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2022, 1, 31 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2022.01.29.22270090", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2022, 1, 31 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2022, 1, 31 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference-count": 0, "references-count": 0, "relation": {}, "score": 1, "short-container-title": [], "short-title": [], "source": "Crossref", "subtitle": [], "subtype": "preprint", "title": [ "Doubtful Clinical Benefit of Casirivimab-Imdevimab Treatment for Disease Severity Outcome of High-Risk Patients with SARS-CoV-2 Delta Variant Infection" ], "type": "posted-content" }