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expert reaction to results from REGAIN trial looking at an online supervised group physical and mental health rehabilitation programme for adults with long Covid after Covid hospitalisation

A study published in the BMJ looks at online supervised group physical and mental health rehabilitation programme for adults with long Covid after Covid hospitalisation. 


Dr Baptiste Leurent, Associate Professor in Medical Statistics, UCL, said:

“This is a well conducted randomised controlled trials, and the findings appear relatively robust, although not unequivocal.  There is limited research on addressing symptoms of long covid and this study is therefore an important contribution.

“The study found a 0.03 higher ‘quality-of-life’ at 3 months for those who received the rehabilitation programme, compared to standard care.  Quality-of-life is a standardised index capturing ‘overall health’, from 0 (death) and 1 (full health).  0.03 is a relatively modest effect, but could be considered sufficient to be worthwhile.

“Looking at the statistical evidence, the p-value when comparing the quality of life between groups was 0.02.  That means that such difference between the groups would have 2% chance to happen if the programme was not making any difference.  This is usually considered encouraging evidence, but not really beyond doubt.

“If we look at all the outcomes the pattern is not very obvious either.  For example, while effects were found on reducing fatigue and pain at 3 months, these were not so clear at 6 or 12 months.  The only clear difference was on self-reported health improvement, with 17% reporting feeling “much better now” compared to 8% in the control group, and this effect was sustained over time.

“A key limitation of such study is that participants are aware of the intervention they receive, and could well score more positively questionnaires if they enjoy the programme.  Without objective measures, it is difficult to disentangle the actual benefit of the programme in addressing long covid symptoms, from the positive perception of receiving such programme.

“Another overlooked limitation are the missing data.  20% of those allocated to the programme did not complete the questionnaires, and it could well be those who enjoy less the programme, or those in poorer health.  This would result in exaggerating any programme benefits.

“With multi-components interventions it is difficult to assess what patients benefited the most from.  Was it the initial discussion, the exercise sessions, or the psychological support?  Do they need to be offered together?  In the same format?  It was interesting to see the programme was all online, making it more easily scalable, but could it be delivered by new staff, with similar effect?

“Overall, this is an interesting research, and provide encouraging findings to address the burden of long covid.  The trial was well conducted and interpreted, but the findings may not be as clear-cut as suggested.  Further analyses are still needed, such as the economic evaluation, to better understand the potential of rolling-out the programme in practice.”


Dr Emily Fraser, Consultant in Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, and clinical lead of the Post COVID clinic in Oxford, said:

“I think this study is good.  The emphasis of this study is not on the biomedical explanation for long Covid (which is proving difficult to pin down) but is instead on what can practically be done to support patients struggling with the after-effects of Covid.  A focus on rehabilitation and holistic care is essential for both management of symptom burden and supporting recovery of these patients, and group programmes that are online and accessible have been shown at our local level to be really beneficial.  Feeling supported, understood and reducing the sense of isolation that many patients have after hospital discharge is really important, alongside setting realistic expectations of recovery and what this looks like.

“One thing I would say (and have done previously), is that this study focuses on a post-hospitalised group who are demographically distinct from the community-managed post-Covid patients we see much more commonly.  I think we therefore need to be careful how we extrapolate the findings to community patients – William, mentioned in the case history, was in intensive care with COVID and so we would anticipate there to be prolonged after-effects of critical illness.  Difficult to draw similarities to a female in their 40s who was previously healthy with a full time job, three kids and an initial relatively mild acute illness – although in both, rehab strategies should remain the focus of course.”


Prof Matt Sydes, Professor of Clinical Trials & Methodology, MRC Clinical Trials Unit (CTU), UCL, said:

“This is data from a randomised controlled trial to address a persistent, international problem.  The trial has an unusual allocation ratio, but its need is explained: the people allocated to the ‘test’ group have sessions together which means some clustering that the researchers needed to account for.

“The press release focuses on the shorter term outcomes (3 months) and on the “much better now” people.  The increase is modest in absolute terms; the absolute number of people with improvement appears small.

“Quite a lot of people stop their participation early, in both groups.  We don’t know whether this means the people contributing to the later timelines were the ones who were at the better end (or the worse end) when joining the trial i.e. the missingness could be relevant.  Either way, it probably impacts a little on how we understand the proportion of people who are doing well.  The gains do seem to increase beyond the 3 month time point, but that increase and improvement continues to be modest and could partly be driven by those people who were doing worse earlier choosing to not contribute later.  Figure 2 zooms in on these estimates without showing the full scale.

“It would be interesting to know more about the duration of symptoms participants had before joining the trial, particularly as people might look to apply the findings now to people who have been living with Long-Covid for a prolonged period.”




‘Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study): multicentre randomised controlled trial’ by Gordon McGregor et al. was published in the BMJ at 23:30 UK time on Wednesday 7 February 2024.

DOI: 10.1136/bmj2023076506



Declared interests

Dr Baptiste Leurent: “No conflict of interest.”

Prof Matt Sydes: “No financial ones that are directly relevant.

Had speaker fees for educational talks (general stats lessons) for AstraZeneca (well, after today), Esai and Janssen.

I sit as a semi-independent (*) member of the Trial Steering Committee for the STIMULATE-ICP trial in Long-Covid (

(*) Not involved in trial but same institution as Chief Investigator.”


For all other experts, no reply to our request for DOIs was received.


This Roundup was accompanied by an SMC Briefing. 

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