Tier 4 — mechanistic

Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era

Brandon P. Verdoorn, Tamara K. Evans, Gregory J. Hanson, Yi Zhu, Larissa G. P. Langhi Prata, Robert J. Pignolo, Elizabeth J. Atkinson, Erin O. Wissler-Gerdes, George A. Kuchel, Joan B. Mannick, Stephen B. Kritchevsky, Sundeep Khosla, Stacey A. Rizza, Jeremy D. Walston, Nicolas Musi, Lewis A. Lipsitz, Douglas P. Kiel, Raymond Yung, Nathan K. LeBrasseur, Ravinder J. Singh, Teresa McCarthy, Michael A. Puskarich, Laura J. Niedernhofer, Paul D. Robbins, Matthew Sorenson, Tamara Tchkonia, James L. Kirkland
Journal of the American Geriatrics Society 2021 69:3023-3033

Bibliography

PubMed
PMID 34375437
PubMed Central
PMC8447437
DOI
10.1111/jgs.17416
Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
National Institutes of Health, Grant/Award Numbers: P01 AG62413, R01 AG063543-S1, R01 AG72301, R33 AG61456, R37 AG13925, U19 AG056278; Noaber Foundation; Robert J. and Theresa W. Ryan; The Connor Fund
Competing interests
Patents on senolytic drugs and their uses are held by Mayo Clinic and the University of Minnesota. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic conflict of interest policies.

Study snapshot

DesignRandomized, placebo-controlled, double-blind secondary prevention pilot study
ModelHuman subjects (skilled nursing facility residents aged 65+)
SampleActual enrollment: 20 participants
InterventionFisetin (~20 mg/kg/day orally or by feeding tube) for 2 consecutive days, repeated one week later (Days 0, 1, 8, and 9)
DurationStudy start 2022-04-29; actual completion 2024-11-30; trial subsequently terminated for futility in the final registry record.
EndpointsPrevention of SARS-CoV-2 disease complications by a 7-point ordinal severity scale; Evaluation of safety and tolerability of Fisetin; Reduction of progression of severity of SARS-CoV-2 infections; Decrease in senescent cells, inflammation, and physical dysfunction (frailty)

What the study showed, in plain terms

COVID-FIS was a Phase 2 randomized, double-blind, placebo-controlled trial testing intermittent high-dose fisetin in older skilled-nursing-facility residents with COVID-19. The 2021 publication describes the scientific rationale and trial design rather than efficacy results.

The final ClinicalTrials.gov record now reports that the trial enrolled 20 participants and was terminated after the Data and Safety Monitoring Board and National Institute on Aging determined that it should stop for futility. Registry results were posted on August 26, 2025.

This trial therefore should not be presented as an ongoing positive test of fisetin. It is completed negative/futility evidence in a specific acute infectious-disease setting and does not directly establish whether fisetin produces senolysis in healthy aging tissues.

Key findings

  • Final trial status: terminated for futility after actual enrollment of 20 participants.
  • The tested regimen used approximately 20 mg/kg/day fisetin for two consecutive days, repeated one week later.
  • Registry results are posted, but the peer-reviewed 2021 paper is a protocol/rationale article rather than a clinical efficacy publication.
  • The trial tested COVID-19 outcomes in frail older adults; it was not a direct tissue-target-engagement study proving or disproving systemic human senolysis.

What this study can and cannot tell us

  • Small actual enrollment and early termination severely limit precision.
  • COVID-19 outcomes are disease-specific and cannot be generalized to healthy-aging or longevity outcomes.
  • The available peer-reviewed publication predates the registry results, so clinical outcome interpretation relies on ClinicalTrials.gov rather than a peer-reviewed results paper.

Related papers in the corpus

Tier 3
Fisetin as a senotherapeutic agent — evidence and perspectives for age-related diseases
Tavenier J et al. · Mechanisms of Ageing and Development · 2024
Tier 3
Fisetin is a senotherapeutic that extends health and lifespan
Yousefzadeh MJ et al. · EBioMedicine · 2018

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability