Writing in Clinical Infectious Diseases, University of Minnesota (U of M) Medical School–led researchers pointed out that a higher viral load usually indicates a greater concentration of the virus. That often can be an indicator of infection severity.
“The results of the study are important because COVID-19 continues to cause illness, both during acute infection and for months after infection,” said Carolyn Bramante, MD, principal investigator and assistant professor at the U of M Medical School.
The study team advised that metformin has antiviral activity against RNA viruses, including SARS-CoV-2. The antiviral activity apparently occurs because of suppression of protein translation via targeting the host mechanistic target of rapamycin pathway.
“In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58% of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%,” the researchers reported.
COVID-OUT was a 2x3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin. For the study, 945 participants self-collected anterior nasal swabs on Day 1, 871 on Day 5, and 775 on Day 10. The researchers then quantified viral load using reverse-transcription quantitative polymerase chain reaction.
The results indicated that the mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (–0.56log10 copies/mL; 95% CI, –1.05 to –.06; P = .027). “Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94),” according to the study team. “Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo.”
The report concluded that the randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2 found that metformin significantly reduced SARS-CoV-2 viral load and the action might “plain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology.”
The research team suggested that metformin treatment for adults recently infected with COVID-19 could reduce the amount of the virus in the nose and keep the amount of virus from becoming elevated again.
“Among the volunteers in this randomized trial, there was a more than 41% reduction of long COVID among those receiving metformin and a 58% reduction in hospitalization by 28 days. This new study explains why this occurred. Metformin reduced the amount of SARS-CoV-2 virus present, which likely accounts for why this $1 medication reduced hospitalizations and long COVID,” said David Boulware, MD, MPH, an infectious disease physician and professor at the U of M Medical School.
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