Safety, Feasibility, and Preliminary Clinical Findings of an Oral Polypore Fungi Combination with Mild-to-Moderate COVID-19: A Randomized, Placebo-Controlled Phase I Clinical Trial

ABSTRACT Background Use of fungal mycelia, which have innate immunity-enhancing and antiviral properties, constitutes a novel early-wave, low-cost, at-home strategy in the early critical months of an outbreak when treatments or mass medical countermeasures are not yet available and the public health recommendations advise quarantining at home. Methods We evaluated safety and feasibility of a fungal mycelial combination (Fomitopsis officinalis and Trametes versicolor, FoTv) for treatment of COVID-19 and explored its antiviral effects and potential to reduce symptoms. In a randomized, double-blind, placebo-controlled (26 FoTv, 24 Placebo), dual site (UCSD/UCLA medical centers) clinical trial conducted under an active FDA Investigational New Drug (IND) application, we examined non-hospitalized patients diagnosed with mild-to-moderate COVID-19 ≤ 96 hours, and experienced symptom onset ≤ nine days, before enrollment. Results FoTv was safe, well-tolerated, and feasible for COVID-19 treatment. Mean values for renal, hepatic, and coagulation markers for both the FoTv and Placebo groups remained within normal levels. Unlike the Placebo, the FoTv group exhibited a minor reduction in estimated glomerular filtration rate across the treatment period, but both groups were equally likely to transition from normal to abnormal levels across the treatment period. Treatment adherence was high (97% FoTv, 95% Placebo) and dropout was low (0% FoTv, 4% Placebo). Exploratory analyses indicated that FoTv significantly reduced the number and severity of symptoms, particularly sore throat/cough, as well as the COVID-19 biomarker, C-reactive protein. A complementary in vitro study indicated that FoTv reduced SARS-CoV-2 (pseudovirus) cellular infection. Conclusions FoTv was safe, feasible, reduced viral cellular infection, and may reduce symptoms of COVID-19 associated with viral transmission. In our recent companion clinical trial, examining FoTv as a COVID vaccine adjunct, we observed a significant reduction in short-term vaccine side effects while preserving—and potentially increasing—long-term anti-SARS-CoV-2 antibody levels over six months (Saxe et al., 2026, BMC Immunology). Taken together, these studies elucidate a blueprint for a novel two-phase public health pandemic intervention. This blueprint involves use of a botanical immunomodulatory product, during the early critical months of an outbreak and, once vaccines become available, to improve their uptake and effectiveness. Trial Registration Clinicaltrials.gov registration: NCT04667247 .