Trials underway for mushrooms as treatment for COVID-19: JAMA

USA: Medicinal mushrooms and Chinese herbs are being tested in ongoing early trials for the treatment of COVID-19 patients with mild to moderate symptoms. An article in JAMA last week described the trials.

After researchers applied for approval in April 2020, the US Food and Drug Administration (FDA) approved the MACH-19 trials (the acronym for Mushrooms and Chinese Herbs for COVID-19). The double-blind, placebo-controlled studies would evaluate the safety and feasibility of treating mild to moderate COVID-19 with either medicinal mushrooms, which have a long history as natural therapeutics for pulmonary disease, or a Chinese herb formulation from Taiwan that's widely used as a COVID-19 remedy in China.

"Researchers are currently conducting in vitro and animal studies with natural products to evaluate direct antiviral activity or to address COVID-19 sequelae," D. Craig Hopp, PhD, deputy director of the Division of Extramural Research at the National Center for Complementary and Integrative Health (NCCIH), said in an interview. But the MACH-19 treatment trials are unique, he noted, because they're evaluating natural products among humans with acute SARS-CoV-2 infection.

The first two phase 1 randomized, double-blind, placebo-controlled trials have begun at UCLA and the University of California San Diego to treat COVID-19 patients quarantining at home with mild to moderate symptoms. A third trial is investigating the use of medicinal mushrooms as an adjuvant to COVID-19 vaccines.

The researchers have also launched the fourth trial testing the mushrooms against placebo as an adjunct to a COVID booster shot. It looks at the effect in people who have comorbidities that would reduce their vaccine response. 

The two mushroom varieties being tested — turkey tail and agarikon — are available as over-the-counter supplements, according to the report. They are a separate class from hallucinogenic or "magic" mushrooms being tested for other uses in medicine.

According to the JAMA paper, for each of the MACH-19 treatment trials, researchers plan to recruit 66 people who are quarantined at home with mild to moderate COVID-19 symptoms. Participants will be randomly assigned either to receive the mushroom combination, the Chinese herbs, or a placebo for 2 weeks. 

D. Craig Hopp, PhD, deputy director of the Division of Extramural Research at the National Center for Complementary and Integrative Health (NCCIH), told JAMA in an interview that he was "mildly concerned" about using mushrooms to treat people with active SARS-CoV-2 infection.

"We know that a cytokine storm poses the greatest risk of COVID mortality, not the virus itself," Hopp said. "The danger is that an immune-stimulating agent like mushrooms might supercharge an individual's immune response, leading to a cytokine storm."

"A cytokine storm is unlikely for these patients because the mushroom components "don't mimic inflammatory cytokines," Stephen Wilson, PhD, an immunologist who consulted on the trials when he was a chief operating officer of the La Jolla Institute for Immunology, said in the JAMA article.

"We think the mushrooms increase the number of immunologic opportunities to better see and respond to a specific threat. In the doses used, the mushrooms perturb the immune system in a good way but fall far short of driving hyper or sustained inflammation," Wilson said.

"Western medicine generally doesn't need help treating infectious diseases until a pandemic like COVID hits," said integrative medicine specialist Andrew Shubov. "That's when we realize we don't have good answers to treating viral respiratory diseases. We hope our trials will open the eyes of the Western world to a rich pharmacopeia of natural substances that we can draw from for many other diseases going forward."

Reference:

Slomski A. Trials Test Mushrooms and Herbs as Anti–COVID-19 Agents. JAMA. Published online November 03, 2021. doi:10.1001/jama.2021.19388