Non-pharmacological and TCM-based Treatment for Long COVID Symptoms

Study Overview
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Brief Summary
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Cognitive impairment is one of the commonly reported Long COVID symptoms, mainly in terms of memory, attention, and executive function. The cognitive symptoms of Long COVID are similar to brain fog or chemo brain, manifested as low energy, disorientation, difficulties in attention and communication which are common conditions in cancer patients after chemotherapy. Given the negative impact of such cognitive impairment in daily living and working, it is important to develop effective treatment and self-management techniques to enhance cognitive functions in COVID-19 survivors. Acupuncture, acupressure, dantian breathing, and qigong are promising treatment and self-management techniques to remedy the cognitive impairment in people with Long COVID. Since acupressure, dantian breathing, and qigong are feasible for self-practice, they can be trained to promote a healthy lifestyle. The present study is a randomized controlled trial to evaluate the efficacy of acupuncture, lifestyle management (including dantian breathing, qigong, and acupressure), and acupuncture + lifestyle management to improve general cognitive function of people with Long COVID symptoms, compared with wait-list control. We will recruit 100 COVID-19 survivors who experience at least mild cognitive impairment and/or self-complaint of cognitive difficulty for at least 12 weeks after clinical recovery from COVID-19 infection. They will be randomly assigned to the following groups: (1) Acupuncture Group; (2) Lifestyle Management Group; (3) Acupuncture + Lifestyle Management Group; and (4) Waitlist Control Group. Acupuncture and lifestyle management will each take 8 weeks, with two 50-min sessions per week. Primary outcome is general cognitive function. Secondary outcomes cover fatigue, physical fitness, neurocognitive function, psychological distress, and health-related quality of life, pro-inflammatory cytokines (IL-6, TNF-α) and salivary cortisol. Assessment will be conducted at baseline, mid-intervention (4 weeks after baseline), post-intervention (8 weeks after baseline), and 4-week follow-up (12 weeks after baseline).

Official Title
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Testing Non-pharmacological TCM-based Treatments for Cognitive Impairment in People With Long COVID Symptoms: A Randomized Controlled Trial

Conditions
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Long Covid19

Intervention / Treatment
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* Behavioral: Acupuncture and TCM-based lifestyle management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With a diagnosis of SARS-CoV-2 infection at least 3 months prior to recruitment (to be verified based on evidence of positive RT-PCR/RAT result) Tested negative of SARS-CoV-2 according to a RAT at the time of recruitment; Fulfill at least one of the following conditions: (a) With at least mild cognitive impairment as assessed with Montreal Cognitive Assessment 5-minute to be conducted by the project team; (b) Self-report of at least one cognitive symptom persisting for 12 weeks or longer after clinical recovery of SARS-CoV-2 infection according to Woods Mental Fatigue Inventory. Exclusion Criteria: Having any severe cognitive impairment, mood disorder, or anxiety disorder before SARS-CoV-2 infection. Having any current psychiatric disorders that require taking medication. Having any current medical conditions that could interfere with cognitive functions. Having epilepsy or any other unstable medical conditions. Having alcoholism or drug abuse within the past 1 year. Having bleeding tendency. Having severe needle phobia. Having heart pacemaker or other electronic devices implanted in the body. Currently participating in another research studies or clinical trials.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acupuncture<br>This is an 8-week (two 50-min sessions per week) treatment of acupuncture on the following fixed acupoints: bilateral Touwei (ST8), Sishencong (EX-HN1), Taiyang (EX-HN5), Shuaigu (GB8), Toulinqi (GB15), and unilateral Yintang (EX-HN3), Baihui (GV20). The treatment will be performed by registered acupuncturists. based on acupuncturists' clinical judgement, acupuncture can be performed on any of the following additional acupoints, including unilateral Shenting (GV24), Shenmen (HT7), Sanyinjiao (SP6), Taichong (LV3), Neiguan (PC6), AND Anmian (EX-HN22). | Behavioral: Acupuncture and TCM-based lifestyle management<br>* Non-pharmacological treatment based on traditional Chinese medicine.<br>|
| Experimental: TCM-based lifestyle management<br>This is an integrated TCM-based training program with components of dantian breathing, Baduanjin, and self-acupressure [Yintang (EX-HN3), Shenting (GV24), Taiyang (EX-HN5), Fengchi (GB20), Neiguan (PC6), Shenmen (HT7), and Sanyinjiao (SP6)]. The treatment will last for 8 weeks (two 50-min sessions per week), and it will include health education and workshops to be delivered by trained research assistants. | Behavioral: Acupuncture and TCM-based lifestyle management<br>* Non-pharmacological treatment based on traditional Chinese medicine.<br>|
| Experimental: Acupuncture + TCM-based lifestyle management<br>This is a combination of the above two arms. The participants who randomly assigned to this arm will received two acupuncture sessions and two sessions on lifestyle management every week, and the intervention duration is 8 weeks. | Behavioral: Acupuncture and TCM-based lifestyle management<br>* Non-pharmacological treatment based on traditional Chinese medicine.<br>|
| No Intervention: Wait-list control<br>Participants will receive no intervention during the whole assessment period. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global cognitive function | Overall status of cognitive function | baseline, mid-intervention (4 weeks after baseline), post-intervention (8 weeks after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global cognitive function | Overall status of cognitive function | baseline and 4-week follow-up (12 weeks after baseline). | 
| Cardiopulmonary function |  | baseline, mid-intervention (4 weeks after baseline), post-intervention (8 weeks after baseline), and 4-week follow-up (12 weeks after baseline). | 
| Fatigue |  | baseline, mid-intervention (4 weeks after baseline), post-intervention (8 weeks after baseline), and 4-week follow-up (12 weeks after baseline). | 
| Health-related quality-of-life |  | baseline, mid-intervention (4 weeks after baseline), post-intervention (8 weeks after baseline), and 4-week follow-up (12 weeks after baseline). | 
| Psychological distress | Depression, anxiety, and stress | baseline, mid-intervention (4 weeks after baseline), post-intervention (8 weeks after baseline), and 4-week follow-up (12 weeks after baseline). | 
| Neurocognitive functions | Attention, processing speed, working memory, and executive function | baseline, mid-intervention (4 weeks after baseline), post-intervention (8 weeks after baseline), and 4-week follow-up (12 weeks after baseline). | 
| Neurobiological outcomes | IL-6, TNF-α, and cortisol | baseline and post-intervention (8 weeks after baseline) |