A phase 3 randomized, controlled trial finds that a single injection of an experimental antiviral treatment slashed hospitalizations and emergency department (ED) visits among high-risk COVID-19 patients when given soon after symptom onset.
Led by Stanford and McMaster university researchers, the study was published yesterday in the New England Journal of Medicine. The team said that one subcutaneous (under-the-skin) dose of pegylated interferon lambda, which marshals the immune system against SARS-CoV-2, is more effective than any other COVID-19 treatment and doesn't rely on patient adherence to a drug regimen.
In the TOGETHER adaptive platform trial, the researchers randomly assigned COVID-19 patients seeking outpatient treatment in Brazil and Canada to receive one injection of pegylated interferon lambda or an injectable or oral placebo.
The patients, 83% of whom were vaccinated, had symptoms for 7 days or less at the time of the visit. All were either age 50 or older or had underlying medical conditions such as diabetes, high blood pressure, organ transplant, or cancer. Conducted from June 2021 to March 2022, the trial spanned the emergence of several SARS-CoV-2 variants, including Omicron.
Most effective when given in first 3 days
Of the 1,951 patients, 931 received pegylated interferon lambda, and 1,018 were given placebo. Twenty-five patients (2.7%) in the interferon group were hospitalized or visited an ED, compared with 57 (5.6%) of placebo recipients, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval [CI], 0.30 to 0.76; probability of superiority to placebo, greater than 99.9%).
The treatment was most effective in those who received the drug within the first 3 days of illness. Results were comparable regardless of vaccination status or dominant variant. An analysis of secondary outcomes yielded similar results, including time to hospitalization (hazard ratio [HR], 0.57; 95% CI, 0.33 to 0.95) and hospitalization or death (HR, 0.59; 95% CI, 0.35 to 0.97).
Patients with a high viral load at baseline who received pegylated interferon lambda had lower viral loads by day 7 than did placebo recipients. Adverse-event rates were similar in the two groups.
'Could save tens of thousands'
The investigators said that pegylated interferon lambda has proven to be safe and likely would be effective against other respiratory viruses, such as influenza. "This discovery allows us to enter a new era where you can have pan-virus interventions against a range of diseases," coauthor Edward Mills, PhD, of McMaster, said in a university news release. "This could save tens of thousands of lives."
Lead author Gilmar Reis, MD, PhD, said the research is ongoing. "The ultimate aim would be using it in combination with Paxlovid, but that needs to be evaluated in a clinical trial setting," he said.
