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We evaluated safety and feasibility of a fungal mycelium-based natural product (\n                      <jats:italic>Fomitopsis officinalis<\/jats:italic>\n                      and\n                      <jats:italic>Trametes versicolor<\/jats:italic>\n                      , FoTv) as an adjunct to human COVID-19 vaccination, as well as its impact on vaccine side-effects and anti-SARS-CoV-2 antibodies (Abs).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Randomized, double-blind, placebo-controlled clinical trial involving adjunctive treatment with FoTv or visually-identical Placebo (dosage: eight 500-mg capsules TID orally for four days) in combination with COVID-19 vaccination. Main outcomes included: Safety (adverse events, renal and hepatic function [Days 1\u201314]); Feasibility (completion rate and treatment adherence); Side-effects (number and severity, self-reported on days 1 [vaccination] to 5); and anti-SARS-CoV-2 Ab levels (receptor-binding domain and Spike, collected from blood drawn on days 1, 3, 14, and 28\/42, and at 6 months).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ninety participants receiving COVID-19 vaccination were randomized to either FoTv (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200952) or Placebo (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200938) groups. There were no adverse events and the groups had overlapping 95% confidence intervals for the percentage of participants transitioning from normal to abnormal renal\/hepatic function when comparing Days 1 and 14. All participants (100%) completed the study and treatment adherence was greater than 95%. Participants with detectable anti-SARS-CoV-2 Abs (from prior COVID antigen exposure) were classified as \u201cCOVID-Exposed\u201d and those with undetectable anti-SARS-CoV-2 Abs as \u201cCOVID-Naive.\u201d FoTv, versus Placebo, significantly reduced side-effects in COVID-Naive individuals, specifically on days 3 and 5, but not in COVID-Exposed individuals. In the COVID-Naive FoTv group, Ab responses were preserved across 6 months (and possibly increased), an effect not observed among other groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>After COVID-19 vaccination, adjunctive FoTv was safe, feasible, and reduced vaccine side-effects without compromising (and possibly increasing) Ab levels up to 6 months in participants without previous SARS-CoV-2 exposure. Use of fungal mycelia was successfully tested as a unique approach to prevent a novel pandemic virus (SARS-CoV-2), with potential application to H5N1\/Bird Flu and other emerging viruses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Trial registered on ClinicalTrials.gov NCT04951336 on June 30, 2021.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12865-026-00809-9","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T09:45:02Z","timestamp":1769852702000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Polypore mushroom mycelia as an adjunct to COVID-19 vaccination: a randomized clinical trial"],"prefix":"10.1186","volume":"27","author":[{"given":"Gordon","family":"Saxe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine N.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrokh","family":"Golshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Shekhtman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolton J.","family":"Bair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chase","family":"Beathard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee A.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauray","family":"MacElhern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Shubov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Slater","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan K.","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoebe","family":"Senowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"809_CR1","unstructured":"Avian Influenza. 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