Summary: Camostat mesylate, an oral medication commonly used to treat pancreatitis, was associated with reduced loss of smell and taste in people with early COVID-19 infection.
Source: Yale
Researchers at Yale School of Medicine found an unexpected benefit of camostat mesylate: patients who received the drug in an early outpatient trial experienced less loss of smell and taste, two prominent symptoms of COVID-19.
In spring 2020, an investigative team led by infectious disease specialist Joseph Vinetz, MD, set out to test whether camostat mesylate—an oral protease inhibitor used in other conditions—could reduce SARS-CoV-2 viral load and improve clinical outcomes in people recently diagnosed with COVID-19. The randomized, double-blind, placebo-controlled Phase II trial ran from June 2020 to April 2021 and enrolled adults who tested positive for SARS-CoV-2 within three days of study entry.
Although camostat mesylate did not produce the anticipated reduction in nasopharyngeal viral load, the trial revealed a notable and clinically relevant effect: participants who received camostat were far less likely to experience anosmia (loss of smell) and ageusia (loss of taste) compared with those assigned to placebo. This unexpected finding has prompted the team to recommend further study of camostat as a potential early treatment to prevent chemosensory dysfunction after COVID-19.
How the finding emerged
Dr. Vinetz and colleagues were initially motivated by laboratory data published in Cell in April 2020 showing that camostat could block SARS-CoV-2 entry into cells. The clinical trial was organized quickly, with collaboration from Anne Spichler Moffarah, MD, PhD, Gary Desir, MD, and Geoffrey Chupp, MD, who oversaw trial operations at Yale’s outpatient site.
Seventy participants were randomized to receive either camostat mesylate (200 mg orally four times daily for seven days) or matched placebo. Although the main trial objective—reducing the four-day nasopharyngeal viral load by at least 0.5 log10 compared to placebo—was not met, the investigators observed faster overall symptom resolution, reduced fatigue beginning after day four, and a striking attenuation of smell and taste loss in the camostat group.
According to the team, patients on camostat reported lower symptom scores on a modified FLU-PRO instrument used to quantify upper respiratory and systemic symptoms, including specific items for smell and taste. The drug was generally well tolerated, with few adverse events reported in the camostat arm.
Loss of smell and taste is a hallmark of COVID-19 for many patients. While these senses return for most people as infection resolves, a substantial subset experience persistent dysfunction lasting months or longer. The Yale investigators note that an accessible, well-tolerated oral medication that prevents chemosensory loss at the onset of infection could have meaningful benefits for quality of life.
Clinical implications and next steps
The trial’s leaders stress that this finding is preliminary and requires confirmation in larger studies. If subsequent Phase III trials validate camostat’s effect on smell and taste preservation, the drug could be considered for early outpatient treatment to prevent these disabling symptoms. Regulatory approval or emergency authorization for this indication would require additional trial data and review by health authorities.
Investigators also emphasize that it remains unknown whether camostat can restore smell or taste once those senses are already lost. The present trial tested prevention at the early stage of infection; therapeutic benefit for established anosmia would need to be addressed in separate studies.
In addition to chemosensory outcomes, the trial reported improved fatigue scores and faster overall recovery among those receiving camostat compared with placebo, with minimal adverse effects reported. These results support further exploration of camostat mesylate as a safe, affordable candidate for early intervention in mild COVID-19.
About this COVID-19 research news
Author: Carrie MacMillan, Yale
Source: Yale
Contact: Carrie MacMillan – Yale
Image: The image is in the public domain
Original research: Preprint report titled “A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste,” by Joseph Vinetz et al., available as a medRxiv preprint. Trial registration: ClinicalTrials.gov NCT04353284.
Abstract
A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste
Importance
Early outpatient treatment of mild SARS-CoV-2 infection may reduce symptom burden and lower the risk of deterioration.
Objective
To evaluate whether oral camostat mesylate reduces upper respiratory SARS-CoV-2 viral load and improves symptoms, including smell and taste, in newly diagnosed outpatients with mild COVID-19.
Design
Randomized, double-blind, placebo-controlled Phase II trial conducted from June 2020 to April 2021.
Setting
Single-site academic medical center outpatient setting in Connecticut, USA.
Participants
Of 568 potential adult participants who tested positive for COVID-19 within three days of screening, 70 were randomized; 498 were excluded for eligibility, interest, or other reasons. Inclusion required a positive SARS-CoV-2 nucleic acid amplification result within three days of screening, regardless of symptoms.
Intervention
Camostat mesylate 200 mg orally four times daily for seven days versus placebo.
Main outcomes and measures
Primary outcome: reduction in four-day log10 nasopharyngeal viral load by 0.5 log10 compared to placebo. Key secondary outcome: change in symptom scores measured by a modified FLU-PRO instrument that included smell and taste items.
Results
Camostat recipients experienced statistically significant improvements in quantitative symptom scores by day 6, faster overall symptom resolution, reduced fatigue beginning after day four, and a marked attenuation of loss of smell and taste compared with placebo. There was no significant reduction in nasopharyngeal viral load at day 4 in the intention-to-treat analysis.
Conclusions and relevance
In this Phase II trial, camostat mesylate was associated with faster symptom recovery and prevention of smell and taste loss, but it did not reduce nasopharyngeal SARS-CoV-2 viral load. Further clinical trials are warranted to confirm these results and to determine whether camostat could play a role in early treatment of mild COVID-19.
Trial registration: ClinicalTrials.gov NCT04353284 (registered 04/20/20)