Saxe G., Smith C.N., Golshan S., Shekhtman T., Bair Z.J., Beathard C., Davis R.A., MacElhern L., Shubov A., Slater D., Kao L.K., Senowitz P., Wilson S. Polypore mushroom mycelia as an adjunct to COVID-19 vaccination: a randomized clinical trial. BMC Immunology. 2026;27(1):24.
Rationale
Using mushroom mycelium as a vaccine adjuvant is a potentially new antiviral strategy — especially relevant amid emerging SARS-CoV-2 variants and pandemic-significant viruses (including H5N1). The authors hypothesized that a short oral course of the FoTv blend alongside COVID-19 vaccination would be safe and feasible, would not increase — and might reduce — vaccine side effects, and would preserve (or enhance) immunogenicity, particularly in people without prior SARS-CoV-2 exposure.
Methods
Design — a randomized double-blind placebo-controlled trial with 6 months of follow-up. Population — 90 adults undergoing COVID-19 vaccination. Intervention — FoTv or visually identical placebo: 8 × 500 mg capsules orally three times daily for 4 days (n=52 FoTv, n=38 placebo). Participants with detectable anti-SARS-CoV-2 antibodies at enrollment were classed 'COVID-exposed', without — 'COVID-naive'. Outcomes: safety (adverse events, kidney/liver function days 1–14); feasibility (completion, adherence); vaccine side effects (number and severity, self-rated days 1–5, day 1 = vaccination day); anti-SARS-CoV-2 antibody levels (RBD and Spike; blood on days 1, 3, 14, 28/42 and at 6 months).
Results
All participants (100%) completed the study; adherence exceeded 95%. No adverse events were recorded; 95% confidence intervals for the fraction of participants whose kidney/liver markers moved from normal to abnormal between days 1 and 14 overlapped between groups. Versus placebo, FoTv significantly reduced vaccine side effects in COVID-naive participants — particularly on days 3 and 5 — while COVID-exposed participants showed no such effect. In the COVID-naive FoTv group the antibody response was sustained through 6 months (and possibly enhanced); no similar pattern in other groups. The abstract does not give exact antibody titers or side-effect effect sizes.
Conclusions
A short adjuvant course of FoTv around COVID-19 vaccination was safe, feasible, reduced vaccine side effects and did not diminish (and possibly increased) antibody levels over 6 months in participants without prior SARS-CoV-2 exposure. The authors suggest mushroom mycelium could be considered a preventive approach against emerging pandemic viruses, with possible application to H5N1.
Identifiers & funding
- Registration: ClinicalTrials.gov NCT04951336 (registered 30 June 2021).
- DOI: 10.1186/s12865-026-00809-9.
- Publication: BMC Immunology, volume 27, article 24 (2026); open access.
- Three co-authors (Z.J. Bair, C. Beathard, R.A. Davis) are employees of Fungi Perfecti LLC (the FoTv manufacturer), as stated in affiliations.
Worth noting
A rare example of a clinical trial of mushroom mycelium specifically as a vaccine adjuvant — and in a peer-reviewed journal, unlike the companion active-COVID paper (still a preprint). Main limitations: small sample (n=90, smaller still in the COVID-naive subgroup) and uneven allocation (52 vs 38) reducing power. The SARS-CoV-2-exposure stratification was post hoc by antibody status rather than pre-stratified, and the 'exposed/naive' label mixes vaccinated and previously-infected people — different immunological backgrounds. The antibody finding is phrased cautiously ('sustained and possibly increased') — its clinical meaning for real protection is unknown, since titer–protection correlation for SARS-CoV-2 is non-linear. As with the companion paper, the material is one manufacturer's dried mycelium and some authors are its employees — caution applies, particularly on self-reported side-effect scales.