Among COVID-19 patients at risk for severe illness, the use of the antiviral molnupiravir (Lagevrio) within 5 days of infection was linked to reduced odds of persistent symptoms and related hospitalization and death, regardless of vaccination status or previous infections, finds a US Department of Veterans Affairs (VA) study.
Led by VA Saint Louis Health Care System researchers, the study was published today in BMJ. The research involved 229,286 veterans who tested positive for COVID-19 from January 5, 2022, to January 15, 2023, and had at least one risk factor for severe disease. The data were collected from 171 VA medical centers and 1,112 outpatient sites.
A total of 11,472 patients received a prescription for molnupiravir within 5 days of diagnosis, and 217,814 received no COVID-19 treatment. Most patients were White men. Follow-up was 1 month.
Reduced odds of eight lingering symptoms
Long COVID was diagnosed at 6 months in 18.58% in the molnupiravir group and 21.55% in the no-treatment group. Relative to no treatment, molnupiravir use was linked to a lower risk of long COVID (relative risk, 0.86; absolute risk reduction at 6 months, 2.97%; absolute reduction in post-acute death hazard ratio, 0.62; absolute reduction in post-acute hospital admission, 0.86).
Molnupiravir was associated with a lower risk of abnormal heart rhythms, blood clots in the lungs, deep vein thrombosis, fatigue and malaise, liver disease, acute kidney injury, muscle pain, and impaired thinking or reasoning. The results held true in unvaccinated people, those who had received one or two vaccine doses, boosted participants, and those with previous SARS-CoV-2 infection or reinfection.
The drug was also tied to a lower risk of long COVID in subgroups based on age, race, sex, smoking status, cancer, cardiovascular disease, chronic kidney disease, chronic lung disease, diabetes, and immune dysfunction compared with no treatment. No statistically significant associations were seen between molnupiravir and ischemic heart disease, diabetes, dysfunction of involuntary body functions, shortness of breath, or cough.
Mechanisms still unclear
The researchers said they don't know whether the findings would apply to people without risk factors for severe COVID-19.
Molnupiravir was associated with a lower risk of abnormal heart rhythms, blood clots in the lungs, deep vein thrombosis, fatigue and malaise, liver disease, acute kidney injury, muscle pain, and impaired thinking or reasoning.
"Furthermore, whether higher dose or more prolonged duration of treatment results in higher risk reduction is also not clear," they wrote. "Also, for the millions of people already experiencing long covid, the question of whether initiation of antiviral treatment in the post-acute phase of covid-19 is effective in treating long covid demands urgent attention."
The mechanisms of molnupiravir in reducing the odds of long COVID are also unclear, the authors said. "It is reasonable to hypothesize that impairing viral replication and reducing severity of acute infection by early use of antivirals may lead to reduced risk of PASC [post-acute sequelae SARS-CoV-2]," they wrote.
"This hypothesis is consistent with the putative mechanisms that are being proposed to explain the occurrence of PASC, including viral persistence, immune dysfunction, occult organ injury during the acute phase that may manifest in the post-acute phase, and microbiome dysbiosis [imbalance]."
