A team of scientists recently conducted a large-scale study at Northwell Health, New York, USA, to evaluate the efficacy of neutralizing monoclonal antibody (MAB) therapies in preventing disease progression among patients with mild to moderate coronavirus disease 2019 (COVID-19). The findings reveal that the timing of initiating MAB therapy is a crucial factor in determining its efficacy against COVID-19. The study is currently available on the medRxiv* preprint server.
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, a continuous effort has been made for developing therapeutic monoclonal antibodies and vaccines against COVID-19. In November 2020, the emergency use authorization for MAB therapies had been issued by the US Food and Drug Administration (FDA) for treating mild to moderate COVID-19 patients who are at high risk for progressing to severe disease or hospitalization. To date, observations made by clinical studies on MAB efficacy remain indecisive, with some showing reduction in viral load and rate of hospitalization with MAB therapies, and some showing no therapeutic benefits against COVID-19.
The operational complexity associated with MAB infusion programs includes staffing requirements during the pandemic, requirements for providing infusions in a COVID-controlled setup, transportation of elderly patients to infusion centers, and the necessity to get timely appointments from service providers.
Northwell Health, a large integrated healthcare system in New York, recently conducted a large-scale MAB infusion program to reduce disease severity, hospitalization rate, and mortality rate among patients with mild to moderate COVID-19.
In the current study, the scientists described the clinical outcomes of almost 3,000 COVID-19 patients who received MAB infusion therapy.
According to the FDA, patients who receive a SARS-CoV-2-positive test report within 10 days of symptom onset and are at high risk for progressing to severe COVID-19 are eligible to receive MAB infusion therapies.
In this report, the scientists described the effectiveness of two MAB therapies, including bamlanivimab and casirivimab/imdevimab. The adult COVID-19 patients who received MAB therapy at ambulatory units or emergency departments between November 2020 and January 2021 were included in the study. The clinical outcomes of MAB-treated patients were compared with those who were eligible but did not receive MAB therapy.
The scientists analyzed the mortality rate in hospitalized COVID-19 patients who received MAB therapy. In addition, they examined the rate of hospitalization and use of emergency facilities within 28 days of a SARS-CoV-2-positive report in outpatients treated with MABs.
A total of 2,818 symptomatic COVID-19 patients (average age: 67 years) who received MAB therapy were analyzed. Hypertension and obesity were the most common comorbidities observed among the patients. The most commonly reported symptoms were cough, malaise, fever, and headache.
In the study cohort, about 89% of the patients received bamlanivimab, whereas 11% received casirivimab/imdevimab. The average duration between symptom onset and MAB infusion was 6 days.
After administering MAB therapy, about 4.4% of patients were presented to the emergency department and released, whereas about 5.1% of patients were admitted to the hospital. The average duration between MAB therapy and emergency department presentation or hospitalization was 3 days. Similarly, the average duration between a positive COVID-19 test and emergency department presentation or hospitalization was 7 days. The majority of patients who required hospitalization after MAB therapy had comorbidities, including diabetes, hypertension, kidney disease, pulmonary disease, and immunosuppressive disease.
To investigate the hospitalization rate, the scientists specifically analyzed a total of 2,721 patients with known symptom onset dates. In this subgroup, the rates of hospitalization for patients who received MAB therapy within 4 days, 5 – 7 days, or more than 8 days of symptom onset were 4.4%, 5%, and 6.1%, respectively.
Of 2,713 patients who were eligible for MAB therapy but did not receive it, about 5% and 7% were presented to the emergency department and hospitalized, respectively, within 28 days of a positive COVID-19 test.
Clinical outcomes of hospitalized patients
To investigate in-hospital mortality, the scientists specifically analyzed 145 in-hospital patients with MAB therapy and 200 in-hospital patients without MAB therapy. The analysis revealed that death occurred to 11% of patients with MAB therapy and 10.5% of patients without MAB therapy.
For further clarification, the scientists conducted a set of statistical analyses to compare the two groups. However, no significant relationship was observed between the pre-hospitalization MAB therapy and time to death.
The study describes the effects of MAB therapy on clinical outcomes of symptomatic COVID-19 patients who are at high risk for disease progression. The findings reveal that the timing of MAB therapy initiation is a crucial determinant of treatment efficacy. The benefits of MAB therapy could be maximized by initiating the treatment soon after symptom onset.
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.