Can an Antiviral Reduce the Taste and Smell Disorder Associated With COVID-19?


Shionogi’s therapy, ensitrelvir, was found to reduce and prevent these issues.

The loss of taste and smell has been one of the ongoing issues some people with COVID-19 encounter and they have varying degrees of persistence that can last a few weeks, and in some cases, up to several months.

As such, investigators wanted to study this phenomenon in patients using the COVID-19 oral antiviral, ensitrelvir, looking at the effects of oral ensitrelvir 125 mg and 250 mg on the resolution of taste and smell disorder in patients with COVID-19 with or without vaccination.

This was a multicenter, randomized, double-blind, placebo-controlled study that was part of the phase 3 SCORPIO-SR trial. According to the investigators, participants were between the ages 12–70 years old, and given either ensitrelvir 125 mg PO (after 375 mg PO loading dose on Day 1 only), 250 mg PO (after 750 mg PO loading dose on Day 1 only) or placebo, once daily for 5 days, and were followed by Day 21 from start of treatment to analyze the proportion of patients presenting with taste or smell disorder.

The results were presented at the recent ID Week and demonstrated a benefit to reducing these comorbidities.

“The proportions of patients with taste disorder or smell disorder were smaller in both the 125 mg and 250 mg groups compared with the placebo group on Day 5 to Day 9,” the investigators wrote. “Significantly smaller proportions of patients had taste disorder or smell disorder on Day 7 and Day 8 in the 125 mg ensitrelvir group, and on Day 8 and Day 9 in the 250 mg ensitrelvir group compared with the placebo group, respectively.”

Ensitrelvir Overview and Regulatory Approval

Ensitrelvir is a selective SARS-CoV-2 3CL protease inhibitor, and received emergency regulatory approval from the Ministry of Health, Labour and Welfare in Japan for COVID-19 treatment in November 2022. Outside of Japan, ensitrelvir is an investigational therapy. In the United States, for example, the FDA granted the antiviral fast track status.

Yohei Doi, MD, professor of Medicine and director of the Center for Innovative Antimicrobial Therapy at the University of Pittsburgh and professor of Microbiology and Infectious Diseases at Fujita Health University was one of the investigators in this study and spoke to Contagion about the agent and the phase 3 trial.


Tsuge Y, Doi Y, et al. Ensitrelvir for the Treatment of COVID-19 Infection: Evaluation of Taste Disorder and Smell Disorder in the Phase 3 Part of the Phase 2/3 SCORPIO-SR Randomized Controlled Trial. Poster #549 presented at IDWeek 2023. October 11-15, 2023. Boston, MA.

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