Trial Report Randomized, waitlist-controlled trial of Cordyceps sinensis mycelium culture extract (Cs4) for long COVID patients in Hong Kong, 2025, Chen et al

[forestglip]

Randomized, waitlist-controlled trial of Cordyceps sinensis mycelium culture extract (Cs4) for long COVID patients in Hong Kong

Yuanyuan Chen, Guang Chen, Cheng Zhang, Guoyi Tang, Yautuen Chan, Ning Wang, Yibin Feng

[Line breaks added]

Abstract
We assessed Cordyceps sinensis mycelium culture extract (Cs4) for alleviating long COVID symptoms. In this randomized trial 110 participants were assigned to receive Cs4 (55 participants) or were waitlisted (55 participants) for 12 weeks.

The primary outcome was the change in long COVID symptom severity at 12 weeks, as measured by the modified COVID-19 Yorkshire Rehabilitation Scale. The secondary outcomes included changes in the Brief Fatigue Inventory Form, Insomnia Severity Index, Hospital Anxiety and Depression Scale, St. George’s Respiratory Questionnaire, and the Short Form 12 health survey at 12 weeks.

Participants receiving Cs4 showed improvement in long COVID symptoms compared to the waitlist control group (MD, −10.1; 95% CI, −14.1 to −6.1; P < 0.001) at 12 weeks. Cs4 recipients also experienced improvement in fatigue (MD, −8.1; 95% CI, −14.2 to −2.0; P = 0.011), insomnia (MD, −2.9; 95% CI, −4.6 to −1.2; P = 0.001), and respiratory symptoms (MD, −6.3; 95% CI, −11.4 to −1.2; P = 0.018). Cs4 also improved the quality of life (physical component MD, 7.0; 95% CI, 4.2–9.8; P < 0.001; mental component MD, 6.8; 95% CI, 2.9–10.7; P < 0.001).

No severe adverse events were reported. Cs4 may be a beneficial treatment for patients with long COVID symptoms.

Link | PDF (Acta Materia Medica) [Open Access]

 

[Jaybee00]

Cs4 placebo could not be blinded due the unique color and smell, therefore the waitlist control group received Cs4 after the first waiting period

 

[Jaybee00]

This product is available on Amazon but for some reason I can’t get the link to show up here. Here it is on iherb.

https://www.iherb.com/pr/mrm-nutrition-cordyceps-cs-4-strain-60-vegan-capsules/4670

 

[Utsikt]

Cs4 placebo could not be blinded due the unique color and smell, therefore the waitlist control group received Cs4 after the first waiting period

Why not use solid coloured capsules?

 

[Mij]

Why not eat the real thing? My Asian friends boil this in a ceramic pot with a lid slowed cooked for 2 hrs.

 

[Hutan]

The authors' take on existing treatment guidance for Long Covid (and ME/CFS):

Guidelines from the National Institute for Health and Care Excellence, the WHO, and the National Institutes of Health offer insights into treatment and management approaches for patients with long COVID. However, these guidelines lack detailed treatment recommendations.

Approaches often stem from small-scale studies or successful interventions in patients with similar conditions. For example, pharmacologic treatments effective for myalgic encephalomyelitis/chronic fatigue syndrome, such as low-dose naltrexone, β-blockers, and alpha-adrenergic agonists, show promise in relieving post-COVID fatigue [10, 11].

Non-pharmacologic methods like cognitive pacing may improve cognitive dysfunction and fatigue caused by COVID-19 [12]. Moreover, some pilot studies have suggested that probiotics alleviate gastrointestinal symptoms [13], while transcutaneous vagal stimulation may mitigate autonomic dysfunction caused by COVID-19 [14].

Taken together, current clinical research targeting long COVID symptoms is limited with most treatments primarily addressing individual symptoms rather than multiple symptoms caused by COVID-19.

Was there going to be a good trial of low dose naltrexone? I'm tired of it being touted as being useful in ME/CFS when there is no good evidence for that.

 

[Hutan]

Cs4 placebo could not be blinded due the unique color and smell, therefore the waitlist control group received Cs4 after the first waiting period

Yes, making this study pretty much useless, unless the improvements were really large.

With the bias probably made worse by selective recruitment and what seems to have been a campaign to hype Cs4 just prior to the trial.

Participants were recruited through a combination of advertisements and the webpage of the School of Chinese Medicine at HKU.

Before the trial began, formative research used qualitative methods, including in-depth interviews and focus group discussions, to assess the feasibility and acceptability of Cs4 for treating post-COVID-19 symptoms. This study followed a participatory research design with researchers and registered traditional Chinese medicine practitioners in Hong Kong contributing to the research design from the proposal preparation stage. The study findings were disseminated through seminars, online forums, and conferences held locally, nationally, and internationally. The participants in the study were informed that the survey data would be used for research purposes.

 

[Hutan]

Measures, with the score ranges

C19-YRSm is the first validated scale describing and grading the severity of long COVID symptoms and functional disability. The scale is comprised of the following 4 subscales: symptom severity, functional ability (range, 0–15 with higher scores indicating a greater impact of symptoms); other symptoms (range, 0–25 with a higher score indicating a greater number of additional symptoms); and overall health (a visual analog scale ranging from 0–10, where higher scores indicated a better health status) [21].

The symptom severity subscale was utilized because this subscale allowed for a comprehensive assessment and quantification of the severity of various long COVID symptoms experienced by participants. The C19-YRSm includes the following symptoms in the symptom severity subscale: breathlessness; cough/throat sensitivity/voice change; fatigue; smell/taste; pain/discomfort; cognition; palpitations/dizziness; post-exertional malaise; anxiety/mood; and sleep. Each item was scored on a scale from 0–3 to indicate severity.

The secondary outcomes included changes in the Brief Fatigue Inventory Form [BFI] (range, 0–90 with higher scores indicating greater severity of fatigue) [22], the Insomnia Severity Index [ISI] (range, 0–21 with higher scores indicating worse sleep quality) [23], the Hospital Anxiety and Depression Scale [HADS] (range, 0–21 with higher scores indicating more severe symptoms) [24], the St. George’s Respiratory Questionnaire (SGRQ), which consists of 4 subscales (symptoms, activity, impact, and total score [range, 0–100 with higher scores indicating greater respiratory severity]) [25], summary scores for the physical and mental components of the Short Form 12 (SF-12) health survey (range, 0–100 with higher scores indicating better health status) [26].