Repurposing a broad-spectrum antiviral drug may help treat asymptomatic, mild COVID-19

The oral antiviral drug umifenovir, which is used to treat influenza, appears to be beneficial in COVID-19 patients who are asymptomatic or with mild symptoms, with a phase III study showing that the drug is well tolerated and can induce viral clearance within 5 days.

At 800 mg administered orally twice daily for a maximum of 14 days, umifenovir was associated with a higher proportion of patients achieving nasopharyngeal swab (RT-PCR) test negativity on day 5—the primary study endpoint—as compared with placebo (73 percent vs 40 percent; p=0.004) among patients with mild or asymptomatic infection. [Int J Infect Dis 2021;doi:10.1016/j.ijid.2021.11.025]

In addition, the group had better clinical recovery with umifenovir than with placebo (p=0.002), as indicated by a greater reduction in the World Health Organization (WHO) score from baseline through day 28.

For patients with moderate COVID-19, the average change in the WHO score was used as the primary endpoint. Patients treated with umifenovir showed faster clinical improvement than those on placebo, although the difference was not statistically significant. However, the investigators acknowledged that the trial included a small number of patients with moderate infection.

“We found that umifenovir was safe and well tolerated, and only a few minor events like headache, stomachache, and nausea were reported,” the investigators said.

“No negative disease progression was noted in both arms, and the patients steadily improved. [Likewise, there were no] deaths reported in either arm,” they added.

Umifenovir has been approved for the treatment of influenza in children and pregnant women from the second trimester onwards in both Russia and China. The investigators believed that the present trial is the first to evaluate the safety and efficacy of umifenovir for SARS-CoV-2 against a placebo control.

“Further, the dosage in the earlier reported trials did not take into account the earlier suggested maximum serum concentration (C_max) of 4.1 µM needed for efficacy of umifenovir against SARS-CoV-2. A single dose of 800 mg of umifenovir in healthy patients were reported to have a C_max of about 4.1 µM, and this corresponds to the half maximal inhibitory concentration (IC₅₀) of ~4.1 251 µM reported against SARS-CoV-2,” the investigators pointed out. [Cell Discov 2020;6:28]

“The reported half-life of ~14–16 hours and the good safety profile of the drug led us to rationally propose a dosage of 800 mg twice a day for the repurposing strategy,” they added.

The study population included 132 COVID-19 patients recruited between October 2020 to April 2021, of which nine discontinued due to various reasons. Of the remaining patients, 82 had mild or asymptomatic infection and 41 had moderate infection.

“Overall, there is an urgent need for effective and safe treatments for COVID-19 patients, and our results demonstrate the efficacy and use of umifenovir in mild–asymptomatic adult COVID-19 patients in the dosage tested here,” the investigators said.

“In view of the safety profile, we suggest [additional] studies to evaluate [the antiviral drug’s] efficacy in children and pregnant/breastfeeding women, too, especially as no other therapeutic is available for this population segments,” they added.

The investigators also called for future investigation of umifenovir as a prophylactic treatment against COVID-19, as such an approach would be useful for high-risk contacts.