Testing the Feasibility of a Self-Help Intervention That Includes Lymphatic Drainage to Reduce Fatigue-Related Symptoms Among Patients with Long COVID in General Practice: Experiences from Our Randomized Controlled Trial (RCT)

Abstract

Introduction

Long COVID-related fatigue affects a large number of people across the world, with increasing numbers of people experiencing long-term disability as a consequence. We tested the feasibility of a self-help version of a manual osteopathic approach initially developed for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to treat people with long COVID-related fatigue.

Methods

Our feasibility study assessed recruitment into a 1:1 randomized controlled trial (RCT) to receive (i) self-help intervention (self-massage, mobility, flexibility, and breathing exercises, and alternating cold and warm packs to the top of the spine) or (ii) wait-list control group. Follow-up was assessed by online surveys at 3 and 6 months (indicating retention). Verbal feedback was obtained from participants.

Results

Of the 138 eligible survey participants, 126 (90.6%) agreed to participate in two RCTs, achieving the required sample size of 100. Follow-up rates of 79.3% and 59.4% were achieved at 3 and 6 months, respectively. Improvements in Chalder Fatigue Questionnaire (CFQ) scores were observed in both groups between 0 and 3 months (− 4.6 and − 2.9, respectively), to a greater degree in the intervention group (p = 0.01). Feedback showed a cohort keen to engage with the intervention, although some found the intervention onerous at times.

Conclusions

We have reported the results of a feasibility study examining a potentially beneficial intervention for people with long COVID. There were indications of benefit in a patient group with often intractable symptoms. Based on this feasibility study, we believe that the low-cost self-help intervention in isolation could help support fatigue reduction in some people. This has implications for the treatment of both long COVID and ME/CFS.

Trial Registration

International Standard Randomized Controlled Trial Number (ISRCTN): 99840264.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-025-01287-z.

Key Summary Points

Why carry out the study?

Long COVID-related fatigue affects millions of people across the world, with increasing numbers experiencing long-term disability as a consequence.

A manual osteopathic approach initially has been developed for people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The purpose of this study was to determine if it was possible to treat people with long COVID-related fatigue with a self-directed adaptation based on the established ME/CFS treatment.

What was learned from the study?

This feasibility study suggests that there were larger reductions in Chalder Fatigue Questionnaire (CFQ-11) scores in the intervention group than in the wait-list group, and the wait-list group, when using the intervention, experienced similar reductions in their scores.

Based on this feasibility study, we believe that the low-cost self-help intervention in isolation could help support a reduction of fatigue in some people.

Introduction

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) was until recently regarded as ‘uncommon’, with a United Kingdom population prevalence estimated between 0.2 and 0.4% [1]. When the (SARS-CoV-2) COVID-19 pandemic arrived in the UK, many of those infected by the virus went on to develop what was eventually described as ‘long COVID’. This term was first described by patients coming together on social media platforms [2]. People became more understanding about the debilitating nature of fatigue, with increasing numbers of people with long COVID being seen across healthcare settings, including in osteopathy and physiotherapy. Following predictions that millions of people would be affected by the condition [3], researchers collecting longitudinal data illustrated the longevity of this condition [4, 5].

In a previous comment paper [6], we outlined the similarities between ME/CFS and post COVID-19 infection fatigue and reported the case of a man with what is now termed as long COVID, whose fatigue was lessened following six sessions with an osteopathic practitioner using an established manual therapeutic approach based on several tenets of osteopathic manipulative medicine such as improving the spinal biomechanics to reduce dysautonomia and to aid blood flow and lymphatic drainage of muscles and the central nervous system through manual soft tissue, cranial and spinal manipulative techniques [7–10].

The treatment involved specific gentle articulatory techniques applied to the thoracic spine, along with cross-fiber and longitudinal soft-tissue manipulation of the paravertebral musculature, as well as effleurage of the superficial lymphatics of the cranium and the cervical and thoracic regions [7, 11] together with nasal release (Table 1). There have been no previous studies using this therapeutic approach in long COVID.

Table 1.

The exact self-help instructions given to participants

Nasal release	Rest elbows on table; place tips of index fingers on either side of the nose (above the bridge); gently pull down/press up for 7 min for the first 10 days, followed by 1 min thereafter
Facial massage	With fingers spread out, apply a little pressure and gently stroke down the face for 20 s (five times taking 4 s each)
Head massage	a. Gently stroke down the side of the head for 20 s each side b. Gently stroke down the back of the head for 20 s
Neck massage (use oil)	Down for 20 s each side simultaneously or one after the other, whichever you find best
Breast massage (use oil)	Up for 1 min each side (NB Divide breast into three sections; outer, middle, and inner, and massage for 20 s each towards the collar bone and not the armpit)
Back massage (use oil)	Up for 1 min each side of the spine (careful not to touch spinal column)
Neck massage–back (use oil)	Down for 20 s each side (simultaneously or one and then the other, whichever you find best)

Similarities in symptoms between people who developed long COVID and ME/CFS led us to test the feasibility of using a self-help version of this approach for people with long COVID in their own homes [12]. This enabled social distancing to be maintained, could be used during ‘lockdown’ periods, and avoided adding to an already-overwhelmed NHS medical system.

Aims

As a feasibility study, our primary aims were to assess recruitment (% of target number recruited into RCT), retention (% providing follow-up data at 3 months and 6 months post the start of the intervention), and data completeness (% complete entries by outcome measure. The secondary aims included: collecting clinical outcome measures of fatigue, physical function, and quality of life.

Methods

The study comprised two stages and was sponsored by Northern Care Alliance (NCA) (https://www.northerncarealliance.nhs.uk). The research involved patients with long COVID in relation to the design and conduct of the study and dissemination of the findings in order to ensure relevance, acceptability, and impact.

Ethical Approval

The ‘Reducing fatigue after long COVID’ randomized controlled trial (RCT) was registered with International Standard Randomized Controlled Trial Number (ISRCTN): 99840264. Ethical approval for the study was granted by London—Chelsea NHS Research Ethics Committee Ref: 21/LO/0809 on 13/01/2023. The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. All participants were given written information about the study and gave written consent.

Participant Recruitment

The study was promoted by (i) the National Institute for Health and Social Care Research (NIHR) Research for the Future (RfTF) team [13], who sent online survey links on our behalf to those on their ‘database of COVID research volunteers’. The study was also promoted by (ii) doctors in the NCA long COVID clinic and (iii) via study team contact details on the ISRCTN entry.

Stage 1: Participants provided ‘implied consent’ by virtue of self-completing a short online survey hosted on the Qualtrics platform [14]. Survey questions (Supplementary Material) included demographic information (gender, age, ethnicity) time since first COVID infection, levels of fatigue (Chalder Fatigue Questionnaire—CFQ-11) [15], physical function (Short Form SF-12) [16], Quality of Life (EQ-5D-5L) [17] and recruitment route (RfTF, or ‘Other’, which could be either NCA long COVID clinician or ISRCTN enquiry).

Participants were automatically allocated a sequential Participant Identification (PID) number within the online survey (via an API Count function). The survey was set to automatically screen stage 1 participants and to ensure that participants met the stage 2 study inclusion/eligibility criteria:

• CFQ-11 of greater than or equal to 4 (when scored dichotomously using 0, 0, 1, 1)

• First COVID-19 infection more than 12 weeks previously

• Participants aged 18 or over

The exclusion criteria were:

• Currently living in a care-home setting

• Pregnancy or breastfeeding

• End-stage heart failure, cancer, major mental illness, and primary sleep disorders (alternative causes of fatigue) or major mental illness

• Dementia diagnosis

• Previous history/current diagnosis of ME/CFS

Those fulfilling the inclusion criteria were provided with a link to the onscreen stage 2 Participant Information Sheet and Consent form, and asked to provide their telephone number, e-mail, and best time to contact them.

Stage 2: Researchers (LR and TM) contacted all participants by telephone. During this call, they provided further details about the study, answered any questions participants might have and completed stage 2 RCT telephone consents. Calls were audio-recorded for audit purposes with participants providing verbal consent. Participant postal addresses were collected once the audio recording had stopped to allow the team to send out the study intervention equipment pack and instructions (TM and AM). PID numbers were added to a secure NHS database to monitor recruitment and retention progress, ensuring timely follow-ups at months 3 and 6.

Randomization into RCT

Randomization was conducted using the online software sealed envelope TM (www.sealedenvelope.com) and was stratified by gender and recruitment route (‘Research for the Future’ or ‘other route’). Within strata, allocation was ‘blocked’ using randomly selected block sizes of 4 or 6. Participants were then allocated to either:

• (i)‘intervention’ group used a patient self-help routine targeting spinal and cranial structure and function plus central lymphatic drainage.
• (ii)‘wait-list’ control group who received the same intervention as in (i) after 12-

Stage 1 data was used as a proxy for stage 2 RCT ‘baseline’ data, avoiding the need to repeat data collection. This also ensured that questions were completed without participant knowledge of their randomization allocation, which might have affected questionnaire completion.

The wait-list design enabled comparison of CFQ-11 change scores between the self-help intervention and the ‘control’ group who received treatment as usual during the first 12 weeks (3 months).

Wait-list participants were able to experience using the intervention after 12 weeks, with 6-month follow-up data allowing comparison of retention between the two study arms. Comparison was only made at the 3-month point, not at 6 months, with the control group. This was a wait-list control study, so there was no control group between 3 and 6 months, rather only between baseline and 3 months. This is now stated in the text.

Intervention

The self-help intervention consisted of a nightly self-undertaken effleurage technique aimed at increasing surface lymphatic drainage down the cranial and cervical region for 2 min and up the thorax for 2 min, front and back, into the central lymphatic drainage at the venous angles plus active head rest for 10 min to aid occipital balance, aimed at improving cranial rhythmicity. Regular gentle rotational exercises five times each way, three times a day, were also given to improve the flexibility of the thoracic spine together with breathing exercises aimed at improving the diaphragm and other muscles of respiration, also to be done three times a day. Participants were also advised to use alternating cold and warm packs self-applied to the mid and upper thoracic spine for a total of 10 min at least once a day (also known as ‘contrast’ bathing).

Participants allocated to the intervention group received a pack with the following items; introductory letter with link to explanatory video, instruction leaflet [18], sweet almond or apricot kernel massage oil, long-handled back massager, gel koolPAK™ and hot water bottle (Fig. 1).

Fig. 1.

Self-help intervention pack as sent to the participants: Hot water bottle, instructions, apricot kernel massage oil, long-handled back massager, and gel warm and cool pack

Participants were asked to follow the instructions on the leaflet and video as much as they were able to, and to record this on an intervention tick sheet provided. Participants were provided with the contact e-mail of our patient liaison officer (OMcD) if they had questions about the intervention, as well as any technical queries to ensure accurate advice was given, and the research team if they had any further study-specific questions.

Follow-Up

This was assessed at 3 months (approximately 12 weeks, by adding 90 days to the consent date). It provided an opportunity for the intervention group to ‘utilize’ the intervention and report back on any changes in symptoms.

Participants were sent an e-mail containing their own unique specific study link to the 3-month and later to the 6-month online surveys. Links were manually generated within Qualtrics (LR) and included PID number, facilitating data linkage across the three survey timepoints. Reminders were e-mailed to non-completers after 2 weeks, and a text alerting them to the e-mails the following week, for participants who had provided a mobile telephone number.

Invitation e-mails were sent by RfTF, which included a survey link (Qualtrics^©) to 391 members of the Coronavirus—Research for the Future (https://researchforthefuture.org/coronavirus/) database between 13/01/2023 and 25/05/2023. RfTF is an initiative to facilitate recruitment to NIHR portfolio studies and other health and care research. By adopting a ‘consent by approach’ model. All volunteers were aged 18+ years. The first participant completed their stage 1 survey on Jan 16, 2023, with recruitment into stage 2 starting Jan 18, 2023. Subsequent recruitment through into stage two was monitored at weekly project meetings and the rate of sending invitation e-mails tailored to ensure target recruitment was met. Ethnicity was provided by self-report. Changes in CFQ-11 score from baseline to 3 months for the intervention vs. wait-list control were compared using a paired t test.

Results

By May 31, 2023, 139 stage 1 survey responses were achieved, yielding a response rate of 38.0%. Automated screening and researcher telephone calls identified 100 eligible stage 2 RCT participants who consented to participate, yielding a 67.0% recruitment rate into our RCT from stage 1 participants. The characteristics of stage 1 and stage 2 participants are provided in Table 2.

Table 2.

Participant characteristics for stage 1 and stage 2

	Stage 1	Stage 2
		Intervention group	Wait-list control group
	139 responses	49 randomized	51 randomized
Age [N; mean (SD); range]	N = 139; 50.9 (13.6); 18–84	N = 49; 51.9 (11.7); 29–77	N = 51; 50.1 (14.3); 18–77
Gender
Female	108 (77.1%)	37 (75.5%)	39 (76.5%)
Male	32 (22.9%)	12 (24.5%)	12 (23.5%)
Ethnicity
White (British/Irish/other)	134 (95.7%) 6 (4.3%)	46 (93.9%) 3 (6.1%)	48 (94.1%) 3 (5.9%)
Other ethnic group
Asian/Asian British	4	2	2
Black/Black British	0	0	0
Mixed/multiple ethnic groups	2	1	1
Recruitment route
RfTF	107 (93.0%)	40 (95.2%)	39 (95.1%)
Other	8 (7.0%)	2 (4.8%)	2 (4.9%)

RftF Research for the Future

Analysis revealed a similar median lag (days) between completion of the baseline data and randomization date for the intervention group of nine, with an interquartile range (IQR) (3, 18) and for the wait-list group 9, IQR (3, 18).

For stage 2 participants, the scheduled 3-month data collection period until August 29, 2023, with the final participant inputting survey data on September 13, yielding a response rate of 79.0% (79/100).

The scheduled 6-month follow-up data collection period ran until November 27, 2023, with two participants inputting survey data that day, achieving a final response rate of 59.0% (59/100) ahead of the survey’s closure.

The CONSORT diagram [19] provides further detail of the participant flow through the study from invitation through study follow-up (Fig. 2).

Fig. 2.

CONSORT Diagram (2010) showing participant flow through stage 1 and stage 2. RftF Research for the Future, RCT randomized controlled trial, Dx diagnosis, CFQ Chalder Fatigue Questionnaire

Stage 1, Survey Recruitment driving stage 2 RCT recruitment: This was successfully achieved within the scheduled 5-month recruitment period and met the recruitment target of n = 100.

Stage 2, Randomization: Randomization was successfully carried out for all 100 participants, with 49 being allocated to the intervention group and 51 to the wait-list control group. One error was identified where an incorrect gender was input during the randomization stage. This was manually corrected and noted, and the corrected gender is presented in the results that follow (Table 2).

Stage 3, Retention: Higher follow-up response rates were seen at 3 months in the ‘wait-list’ control group than in the ‘intervention’ group. The overall attrition (dropout) rate in stage 2 was 21.0%, with rates being 30.6% in the intervention group and 11.8% in the wait-list control group. Eighteen of the remaining 45 participants in the wait-list group at 3 months dropped out by 6 months.

Data Completeness

Across all clinical secondary outcome measures, only one element of the EQ-5D, the visual analogue scale of how participants were feeling on a score of 0–100 was omitted (99.% complete responses).

No serious adverse reaction events (SAR/Es) were reported by participants during their 12-week use of the intervention.

Although not formally powered to test the efficacy of the intervention, i.e., its ability to change fatigue levels, we compared the change in fatigue scores (using 0, 1, 2, 3 item scores) between 0 and 3 months as an indicator of effect in the intervention group compared with the wait-list group. We adopted an intention-to-treat (ITT) approach, assuming participants utilized the treatment for the group they were allocated to.

Importantly, a greater reduction in fatigue-related symptoms was observed when analysis was limited to those participants providing both 0- and 3-month data (Table 3). The individual responses in terms of CFQ-11 changes from baseline to 3 months are shown in Fig. 3.

Table 3.

Change in mean Chalder Fatigue Questionnaire from 0 to 3 months by RCT arm

	Baseline	Baseline (if completing 3-month follow-up)	Baseline (if completing 6-month follow-up)	3-month follow-up	Change (b − a)	3-month follow-up (if completing 3-month follow-up)	6-month follow-up
Intervention	N = 49 Fbar = 25.5 (σF = 5.2) F50 (IQR) = 26 (22, 29)	N = 34 Fbar = 27.1a (σF = 3.4) F50 (IQR) = 27 (25, 29)	N = 30 Fbar = 26.3 (σF = 4.5) F50 (IQR) = 27 (24, 29)	N = 34 Fbar = 22.5b (σF = 7.0) F50 (IQR) = 23 (21, 28)	− 4.6	N = 27 Fbar = 23.6 (σF = 6.9) F50 (IQR) = 25 (21, 29)	N = 30 Fbar = 21.6 (σF = 7.2) F50 (IQR) = 22 (16, 28)
Wait-list control	N = 51 Fbar = 26.3 (σF = 4.7) F50 (IQR) = 27 (23, 30)	N = 45 Fbar = 25.9a (σF = 4.8) F50 (IQR) = 25 (23, 30)	N = 29 Fbar = 26.4 (σF = 4.9) F50 (IQR) = 27 (24, 31)	N = 45 Fbar = 23.0b (σF = 5.9) F50 (IQR) = 24 (18, 27)	− 2.9	N = 27 Fbar = 24.1 (σF = 6.0) F50 (IQR) = 24 (20, 28)	N = 29 Fbar = 19.0 (σF = 7.3) F50 (IQR) = 20 (13, 24)

The 3-month results in bold font are the primary outcome

F_bar (σ_F) mean of Chalder Fatigue Questionnaire (standard deviation), F₅₀ (IQR) median of Chalder Fatigue Questionnaire (inter-quartile range), RCT randomized controlled trial

Fig. 3.

Change in CFQ-11 from baseline to 3 months, indicating individual responses by trial arm group. The arrows indicate the change in CFQ-11 score. The X-axis refers to each individual participant. CFQ Chalder Fatigue Questionnaire

Participants felt that future work would benefit from addressing the time required to complete the intervention; improving video accessibility and including ways to record other changes such as reduced pain. Where participants reported an improvement in fatigue, they felt a desire to continue using the self-help intervention until they returned to normal functioning.

Discussion

Although not formally powered to test for change, the feasibility data indicate larger reductions in CFQ-11 in the intervention than the wait-list group, and the wait-list group when using the intervention experienced similar reductions in their scores (Table 3).

There were indications of benefit in a patient group with often intractable symptoms. We provide preliminary evidence that warrants further evaluation of this intervention. Based on this feasibility study, we believe that the self-help intervention in isolation could help support a reduction of fatigue in some people.

RCTs are usually costly to run and failure to recruit is often a barrier. Collaboration with Research for the Future (RfTF) helped us to meet and achieve our two-stage recruitment targets, with 82% stage 2 participants recruited via this route.

The technique employed is an established manual therapeutic approach based on several tenets of osteopathic manipulative medicine such as improving the spinal biomechanics to reduce dysautonomia and to aid blood flow and lymphatic drainage of muscles and the central nervous system through manual soft tissue, cranial and spinal manipulative techniques [7–11].

The remote methodology, with centralized research support, enabled the study to run in the highly constrained research environment post-COVID-19 UK lockdown. This also spared people with fatigue from further attending clinic appointments and reduced the risk of infection transmission.

Adopting a wait-list methodology meant that all participants who consented to participate would at some point either immediately or after 12 weeks receive the self-help intervention. This may have helped drive study recruitment, as it avoided half the participants from receiving ‘treatment as usual’. All participants had baseline data collected prior to randomization, reducing any bias in reporting, once allocation was known.

Importantly, the groups were balanced in terms of gender and recruitment route, which were controlled for within the randomization process.

Based on participant feedback, we updated the self-help component. Changes included providing a full rationale for using the technique and re-recording the online video guidance with indexed search functionality for easier access to specific areas of support. We recognize the need to convey this to users to motivate them to perform the self-help aspect. Future work will utilize this updated guidance.

The 3-month and 6-month follow-up dates were calculated by adding 90 and 180 days to the consent date; this allowed for some of the delays in utilizing the pack that occurred due to (i) difference between baseline data collection and randomization date (9 days) plus (ii) time for participants to receive the intervention pack (3 days; 1 day for collection of pack from post room and 2 days for Royal Mail delivery. This brings the time that participants can experience use of the intervention closer to the 12 weeks (84 days) intended.

Between 0 and 3 months, retention rates in the study were good, with 79% being on the border between Amber (50–79%) and Green (80–100%) in the Red Amber Green (RAG) ratings often seen in feasibility study protocols [20]. These are purely arbitrary boundaries that were not pre-published for this study per se, but represent when modifications should be made to improve study retention.

It is unusual to see a higher follow-up response rates in ‘control’ compared to ‘intervention’ arms, 88.2% vs. 69.4%, respectively. The reason for this is likely to be twofold: firstly, completing the follow-up survey for those in the wait-list group triggered dispatch of their equipment packs, allowing them to begin using the intervention; secondly, those in the intervention group who had not adhered to the intervention may not have wanted to provide follow-up data.

Interestingly, at 6 months, there was a reverse in this trend, with a larger proportion of non-completers in the wait-list arm than the initial intervention arm, resulting in similar 6-month follow-up rates overall, 61.2% vs. 56.9%, respectively.

Our results suggest that there was an interest within the long COVID community for this type of intervention to be delivered remotely. It remains to be seen as to whether the decline in COVID infection and its potential decrease in severity will lead to a reduction in the number of new long COVID cases arising and whether a similar recruitment could be achieved in future studies.

Further research is warranted, powered to test the effect size of the intervention for an efficacy RCT. Using baseline data from all 100 participants in the current feasibility study, an estimate of the upper 80% confidence interval for the standard deviation of the CFQ is 5.5 units. Assuming an attrition rate of 30% between baseline and the primary endpoint (at 3 months), we calculate that 230 participants would be required in each group (460 in total) to detect a two-point reduction in CFQ scores with 90% power. This could either be as a stand-alone intervention or in conjunction with delivered in-person sessions that focus on lymphatic drainage though specific massage and cranial osteopathic techniques. Introducing a third arm would increase the total sample size to 690. There would also need to be an adjustment for making multiple comparisons.

For individuals who are housebound or not able to attend the hospital because of mobility issues, this is an ideal approach, and so fills a gap in existing care provision.

Our team currently believes that many of those with long COVID after 12–18 months will develop ‘long’ long COVID and are likely to be diagnosed with ME/CFS in the future. This is similar to the progression seen following glandular fever, to post Epstein–Barr Virus (EBV) syndrome, then to ME [21].

Spontaneous remission in long COVID is higher than in ME [22] (evidenced by three participants (5.9%) returning intervention packs after 3 months in the wait-list arm of the trial). Future trials could address this by considering the inclusion of two types of patients, namely participants with long COVID and those with diagnosed ME/CFS as a distinct other group.

A point to take into account is that the wait-list control group was given access to the intervention after 12 weeks, providing an opportunity to experience the same use of the intervention, although some authors suggest that this might contribute to a nocebo effect where waiting to access a treatment limits participants’ self-healing behaviors [23].

Strengths and Limitations

As a feasibility RCT, we aimed to compare recruitment and retention of those using a self-help intervention to reduce long COVID-related fatigue. While the two-stage approach worked remotely, it is uncertain if the same enthusiasm for the study and its methodology would remain now that there are no further COVID lockdowns.

The wait-list strategy was employed so as to give all participants access to the treatment. This is in keeping with good osteopathic research and medical research practice. The higher attrition rate in the intervention group is thought to be related to the time required each day to undertake the self-help intervention as supported by the participant interviews.

We accept that a wait-list control has the potential for exaggerated effect sizes/bias in intervention effect estimates and difficulties in attributing improvements to the intervention itself (vs. natural recovery). However, this was not the primary focus of our study. Participants in the wait-list group were happy enough to wait their turn for the intervention, but there was an obvious drop in numbers in the intervention group after the 3-month follow-up. We cannot say whether this was simply fatigue or whether it was due to the intervention itself.

It is possible that many of those who were lost to follow-up either did not comply with the intervention or experienced side effects. Without carrying out qualitative interviews with all participants, this is impossible to ascertain.

Conclusions

We have reported the results of a feasibility study examining a potentially beneficial low-cost intervention for people with long COVID. There were indications of benefit in a patient group with often intractable symptoms. We provide preliminary evidence that warrants further evaluation of this intervention. Based on this feasibility study, we believe that the self-help intervention in isolation could help support a reduction of fatigue in some people.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Lisa Riste led the writing of the paper with the help of Raymond Perrin and Adrian Heald. Mark Hann undertook the statistical analysis. Lisa Riste organized the paper format. Technical support was provided by Thomas Mulholland with expert input from Olivia McDonald.

Funding

Stage 1 and stage 2 of this study were funded by the Fund for Osteopathic Research into ME (FORME) Registered Charity number 1045005 (Awarded September 2021). The Rapid Service Fee was funded by the authors.

Data Availability

De-identified data are available from the corresponding author on reasonable request.

Declarations

Conflict of interest

Raymond Perrin developed the intervention, which was adapted here. Raymond Perrin is also Research Director (a non-trustee role) for FORME. Adrian Heald, Mark Hann, Lisa Riste, Thomas Mulholland, and Olivia McDonald have nothing to disclose.

Ethical Approval

The ‘Reducing fatigue after long COVID’ randomized controlled trial (RCT) was registered with International Standard Randomized Controlled Trial Number (ISRCTN): 99840264. Ethical approval for the study was granted by London—Chelsea NHS Research Ethics Committee Ref: 21/LO/0809 on 13/01/2023. The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. All participants were given written information about the study and gave written consent.