A polypore mushroom mycelia supplement may reduce adverse effects and help sustain antibody responses after COVID vaccination, according to a randomized, double-blind, placebo-controlled trial published in BMC Immunology.

Benefits appeared only in COVID-naive individuals, with no significant effect in those with prior exposure to SARS-CoV-2 exposure. If confirmed in larger trials, this low-cost approach could improve vaccine acceptability by easing concerns about side effects while supporting more durable immunity.

Preclinical Basis

Studies have revealed that vaccination with mushroom extracts improves protection against pathogens, including influenza virus and SARS-CoV-2. The researchers attributed these effects to the immunomodulatory and antiviral properties of fungal compounds, such as beta-glucans.

Human Evidence

Conducted from June 2021 to January 2022, the study by Gordon A. Saxe, MD, PhD, MPH, Department of Family Medicine, University of California San Diego, and colleagues enrolled 90 individuals receiving COVID vaccination (first dose, second dose, or booster). It was the first placebo-controlled human trial of this approach.

The researchers evaluated FoTv, a product combining extracts of Fomitopsis officinalis and Trametes versicolor. Participants were randomly assigned to FoTv (n = 52) or placebo (n = 38). Both groups received eight 500-mg capsules three times a day orally for 4 consecutive days, starting on the vaccination day. A total of 90 participants (100%) completed the study, with treatment adherence exceeding 95%.

Benefits in COVID-Naive Individuals

The results showed the benefits of FoTv only in COVID-naive individuals — those with no prior COVID infection receiving their first vaccine dose. FoTv recipients reported significantly fewer vaccine-related adverse events on days 3 and 5 and significantly fewer severe events on day 5 (day 3 trend was nonsignificant) than placebo recipients. No significant differences were observed between the FoTv and placebo groups in individuals with prior SARS-CoV-2 exposure.

The same pattern was observed for antibody responses against the receptor-binding domain and spike protein. Among COVID-naive individuals, FoTv recipients showed more sustained antibody levels over 6 months than the placebo recipients; this effect occurred only in those without prior SARS-CoV-2 exposure.

Researchers’ Interpretation

“In the COVID-naive stratum, reduced reactogenicity is consistent with an anti-inflammatory effect of FoTv. FoTv also produced preserved or more gradual anti-SARS-CoV-2 antibody (Ab) trajectories and ultimately numerically higher peak Ab responses than placebo, suggesting it may have facilitated a well-regulated immune response and led to sustained, long-lasting immunity,” the authors wrote.

Beyond the efficacy of such supplements, which remains to be confirmed by further research, these inexpensive, naturally derived products could facilitate vaccine acceptance by addressing concerns about side effects and short-lived immunity.

“More research is needed to elucidate precise mechanisms of fungal immunomodulation and specific clinical applications of fungi. However, the basic approach of using fungi as vaccine adjuncts appears to be safe and feasible, can be brought to bear rapidly, and may work with both mRNA and non-mRNA vaccines as well as with vaccines for other diseases,” the researchers wrote.

The researchers also highlighted that, in addition to COVID, other emerging infectious diseases warrant close attention. Among these, the highly pathogenic avian influenza A (HPAI) virus is of particular and growing concern.

Studies have shown that F officinalis exhibits significant antiviral activity against the H5N1 influenza virus. HPAI is caused by a viral subtype of H5N1 against which the human population is immunologically naive, and which could emerge at any time.

This story was translated from MediQuality, part of the Medscape Professional Network.