Search Continues for a Treatment that Reduces Long COVID Symptoms

The first randomized, placebo-controlled clinical trial evaluating the impact of therapeutic monoclonal antibodies on the risk of developing long COVID was led by researchers at Weill Cornell Medicine. The study, published Sept. 1 in eClinicalMedicine, details an international, multicenter phase 2/3 clinical trial that found a combination of amubarvimab and romlusevimab did not reduce the occurrence of long COVID symptoms.

Lasting weeks or even months after SARS-CoV-2 infection, long COVID is characterized by a variety of symptoms that affect each person differently. These include extreme fatigue, difficulty concentrating, muscle weakness, joint pain and memory problems. According to a National Academies report, approximately 15 to 20 million Americans and more than 60 million globally had long COVID at some point.

The study, led by Dr. Teresa Evering, assistant professor of medicine in the division of infectious diseases at Weill Cornell Medicine and an infectious disease physician at NewYork-Presbyterian/Weill Cornell Medical Center, evaluated how antibody treatment, given during acute infection, impacted after-recovery outcomes at nine months.

The research team analyzed data collected as part of ACTIV-2, a clinical trial designed to evaluate the safety and efficacy of investigational therapeutics for treating nonhospitalized adults with mild-to-moderate COVID-19. Conducted in 2021, this trial included more than 800 people at high-risk of severe COVID-19 in the United States and five other countries. The study population was mostly unvaccinated against COVID-19 and enrolled before omicron variants of the SARS-CoV-2 virus emerged.

Previously, Dr. Evering and colleagues showed that those treated in the trial with the antibodies amubarvimab and romlusevimab during acute infection were 79 percent less likely to be hospitalized or die of COVID within four weeks than those who had received a placebo.

For this new study, the researchers assessed the “symptom diary” that trial participants kept for nine months after treatment, in which they recorded the severity of an array of 27 symptoms typical of long COVID. Participants also completed two health-related quality of life questionnaires. The antibody combo continued to provide protection against hospitalization and death through this period. The researchers, however, saw no significant difference in the self-reported symptoms of long COVID for those who received treatment versus a placebo.

“Future research should focus on identifying the mechanisms underlying long COVID, especially in relation to how different therapeutic agents for acute COVID-19 may influence longer term outcomes,” Dr. Evering said. "Additional large-scale randomized, placebo-controlled studies are needed to assess the efficacy of early interventions in reducing long COVID prevalence.”

This study was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.