In a recent study posted to the medRxiv* preprint server, researchers tested the efficacy of sotrovimab, a neutralizing monoclonal antibody (mAb), in non-hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. They reported how sotrovimab prevented progression to severe coronavirus disease 2019 (COVID-19) and associated hospitalizations and deaths.
Background
The United States (US) Food and Drug Administration (FDA) approved emergency use authorization (EUA) of several mAbs early in the pandemic. One such mAb, sotrovimab, demonstrated high efficacy in reducing hospitalization and progression to severe disease course among high-risk outpatients in trials conducted before the emergence of the SARS-CoV-2 Delta variant of concern (VOC).
Following EUA approval for sotrovimab, clinical trials assessing its clinical outcomes or mortality concerning coronavirus disease 2019 (COVID-19) were sparse. Also, enrolling patients in randomized controlled trials became more challenging. However, as of January 24th, 2022, sotrovimab is the only authorized mAb for outpatient COVID-19 treatment.
In such a scenario, and amid the emergence of new SARS-CoV-2 VOC Omicron, additional real-world data supporting the clinical effectiveness of sotrovimab is crucial for informing policy and clinical practice decisions.
About the study
In the present propensity-matched observational study conducted in Colorado, researchers enrolled 10,036 patients who contracted SARS-CoV-2 infection between October 1st, 2021, and December 11th, 2021, when the SARS-CoV-2 Delta VOC was predominant. They developed a novel real-world evidence platform to assess the clinical impact of sotrovimab therapy on high-risk symptomatic COVID-19 outpatients, followed up for a minimum of 28 days.
The researchers obtained the study data from the electronic health record (EHR) of UCHealth, the largest health system in Colorado, and merged this data with statewide data on vaccination status and COVID-19 mortality from the Colorado comprehensive immunization information system and Colorado vital records, respectively.
EHR data confirmed the patient’s first SARS-CoV-2 positive test date (or the date of start of mAb therapy). The team randomly imputed missing test dates using the normally observed time between SARS-CoV-2 infection to mAb administration.
The researchers performed nearest neighbor propensity matching using logistic regression with treatment status as the outcome, which matched 1,563 untreated patients with 522 sotrovimab-treated patients, i.e., in a ratio of 3:1.
The propensity model accounted for gender, age, ethnicity, race, immunocompromised status, obesity and other comorbid conditions, vaccine doses at the time of infection (zero, one, two, three), and insurance status. Lastly, they assessed the effectiveness of matching using standardized mean differences (SMDs) with a threshold of 0.1.
The primary outcome of the study was hospitalization within 28 days of a positive SARS-CoV-2 test, and there were several secondary outcomes – 28-day all-cause mortality, in-hospital mortality, emergency department (ED) visit within 28 days, and intensive care unit (ICU) length of stay (LOS). Notably, the researchers considered the index visit for hospitalization and ED visits during the analysis.
The researchers used Kaplan-Meier curves to assess the cumulative incidence patterns by treatment status for 28-day hospitalization and also performed two sensitivity analyses.
Study findings
Sotrovimab-treated COVID-19 outpatients showed a much-lower hospitalization rate in comparison to mAb-untreated controls during the Delta variant phase (2.1% vs. 5.7%); accordingly, the authors noted a 63% decrease in the adjusted odds ratio (aOR) of hospitalization, reinforcing the efficacy of sotrovimab treatment. Interestingly, vaccination also decreased the odds of hospitalization, with a more pronounced decrease observed with an increase in vaccine doses.
Sotrovimab therapy reduced mortality odds by 89% in 28 days (aOR:0.11); however, it did not change the odds of visiting the ED (aOR:1.12). The unadjusted number needed to treat (NNT) of 28 to prevent one hospitalization for the untreated group further supported sotrovimab effectiveness against Delta VOC.
A time-to-event analysis revealed that the benefits of sotrovimab therapy accrued on an average of nine days of treatment. Importantly, sensitivity analyses did not alter the results and scientific conclusions of the current study.
Conclusions
Based on the study findings, the authors recommended continued clinical use of sotrovimab, especially for patients with a high baseline risk for hospitalization. Additionally, sotrovimab could prevent the progression to severe COVID-19 and subsequent hospitalization among the elderly (over 65 years), obese, partially vaccinated, unvaccinated, or individuals with comorbid conditions, such as hypertension and pulmonary disease. Furthermore, the study findings could guide the decision-making of policymakers and clinicians amid shortages of mAb supplies and infusion capacity.
In vitro studies suggest that sotrovimab could also effectively neutralize Omicron because it targets non-receptor-binding motif (RBM) epitopes conserved across many sarbecoviruses. However, future studies should examine sotrovimab effectiveness against Omicron in real-world settings to reaffirm the in vitro findings.
*Important notice
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
