Monoclonal Antibody Therapy Effective at Reducing Risk of Death From COVID-19 in Unvaccinated, Vaccinated Patients


Neutralizing monoclonal antibody therapies found to improve outcomes for unvaccinated and nonhospital patients at high risk of poor outcome for SARS-CoV-2.

Neutralizing monoclonal antibody (nMAb) therapy is strongly associated with reduced risk of death within 30 days of contracting COVID-19 in patients who were not hospitalized with COVID-19, according to a new study published in JAMA Network Open. The strength of this association varied with risk of poor outcome and variant type.

Credit: oz -

Credit: oz -

“The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes,” the study authors wrote. By variant, “nMAb treatment was associated most strongly with reduced risk of poor outcomes in patients infected with the Delta variant.”

nMAb therapies improve outcomes for unvaccinated and nonhospital patients at high risk of poor outcome by binding to the spike protein of SARS-CoV-2. Several studies show that they are effective and safe, but many are limited by small sample size, homogenous study populations, and short study periods.

Investigators conducted this retrospective cohort study to evaluate the safety of 4 nMAb therapies and their association with reducing the risk of hospitalization, death, and other adverse outcomes. The findings were stratified by clinical risk and SARS-CoV-2 variants.

The primary outcomes of the study were all-cause emergency department (ED) visits, hospitalization, death, and a composite of hospitalization or death within 14 or 30 days of the date of the first positive COVID-19 test and/or referral date.

The cohort included 167,183 non-hospitalized patients with COVID-19 who were eligible for nMAb treatment. Among patients, 25,241 were treatment with 1 of 4 nMAbs (18.8% bamlanivimab, 7.7% bamlanivimab-etesevimab, 65.9% casirivimab-imdevimab, and 7.6% sotrovimab). Those treated with an nMAb were more likely to be male, White, non-Hispanic, and have at least 1 comorbidity.

At 14 days, patients treated with nMAbs were 24% less likely to visit the ED and had 48% lower risk of hospitalization. Patients in the treatment arm also had 86% lower odds of death within 30 days compared to untreated patients.

“These findings suggest that risk-targeting strategies are important for optimizing outcomes in patients receiving nMAbs for the treatment of COVID-19,” the study authors wrote in the article.

The strength of the association between treatment and reduced risk of hospitalization was larger in unvaccinated patients, which could be attributed to unvaccinated patients having a higher risk-adjusted baseline probability of hospitalization within 2 weeks. The association between nMAbs and the reduced risk of death was also stronger in immunocompromised patients.

nAMbs also had a stronger association with reduced risk of adverse outcomes by variant. The association was observed in patients infected with the Delta variant more than patients infected with Omicron, although the authors note that immunocompromised patients benefitted more from treatment for the Omicron BA.1 epoch.

There is a risk that outcome data were missing from this study, according to the authors. Along with this limitation, the study also did not examine the specific cause of death or primary diagnosis in ED patients.Investigators did not investigate confounding variables including income and primary language spoken, measures of acute infection severity, or granular data on lower-grade adverse events (AEs).

“Despite the fact that no nMAb products currently have [emergency use authorization] for outpatient COVID-19 treatment, the variation in effect sizes by a priori risk of a poor outcome has important clinical implications for future COVID-19 and other disease treatment practices,” the study authors wrote. “This study’s results revealed that when demand for a therapy exceeds supply, risk targeting is an important approach to identify individuals who would benefit most from treatment. Furthermore, even when there is no scarcity of supply, it is important for clinicians to treat patients who will benefit most, especially in scenarios in which a patient may experience an adverse event or a financial burden due to accepting treatment.”


Ambrose N, Amin A, Anderson B, et al. Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes. JAMA Netw Open. 2023. doi:10.1001/jamanetworkopen.2023.9694

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