Review Interventions for the management of long covid post-covid condition: living systematic review, 2024, Zeraatkar, Flottorp, Garner, Busse+

Interventions for the management of long covid post-covid condition: living systematic review
Dena Zeraatkar; Michael Ling; Sarah Kirsh; Tanvir Jassal; Mahnoor Shahab; Hamed Movahed; Jhalok Ronjan Talukdar; Alicia Walch; Samantha Chakraborty; Tari Turner; Lyn Turkstra; Roger S McIntyre; Ariel Izcovich; Lawrence Mbuagbaw; Thomas Agoritsas; Signe A Flottorp; Paul Garner; Tyler Pitre; Rachel J Couban; Jason W Busse

OBJECTIVES
To compare the effectiveness of interventions for the management of long covid (post-covid condition).

DESIGN
Living systematic review.

DATA SOURCES
Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials from inception to December 2023.

ELIGIBILITY CRITERIA
Trials that randomised adults (≥18 years) with long covid to drug or non-drug interventions, placebo or sham, or usual care.

RESULTS
24 trials with 3695 patients were eligible. Four trials (n=708 patients) investigated drug interventions, eight (n=985) physical activity or rehabilitation, three (n=314) behavioural, four (n=794) dietary, four (n=309) medical devices and technologies, and one (n=585) a combination of physical exercise and mental health rehabilitation.

Moderate certainty evidence suggested that, compared with usual care, an online programme of cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference −8.4, 95% confidence interval (CI) −13.11 to −3.69; Checklist for Individual Strength fatigue subscale; range 8-56, higher scores indicate greater impairment) and probably improves concentration (mean difference −5.2, −7.97 to −2.43; Checklist for Individual Strength concentration problems subscale; range 4-28; higher scores indicate greater impairment).

Moderate certainty evidence suggested that, compared with usual care, an online, supervised, combined physical and mental health rehabilitation programme probably leads to improvement in overall health, with an estimated 161 more patients per 1000 (95% CI 61 more to 292 more) experiencing meaningful improvement or recovery, probably reduces symptoms of depression (mean difference −1.50, −2.41 to −0.59; Hospital Anxiety and Depression Scale depression subscale; range 0-21; higher scores indicate greater impairment), and probably improves quality of life (0.04, 95% CI 0.00 to 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; range −0.022-1; higher scores indicate less impairment).

Moderate certainty evidence suggested that intermittent aerobic exercise 3-5 times weekly for 4-6 weeks probably improves physical function compared with continuous exercise (mean difference 3.8, 1.12 to 6.48; SF-36 physical component summary score; range 0-100; higher scores indicate less impairment).

No compelling evidence was found to support the effectiveness of other interventions, including, among others, vortioxetine, leronlimab, combined probiotics-prebiotics, coenzyme Q10, amygdala and insula retraining, combined L-arginine and vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, a mobile application providing education on long covid.

CONCLUSIONS
Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid.

SYSTEMATIC REVIEW REGISTRATION
Open Science Framework https://osf.io/9h7zm/


Link | PDF (BMJ) [Open Access]

 

The only possible reason for this group of people co-authoring a paper is to further a political objective. Unlike a proper review this is written by a collection of people whose only link is a preconceived idea that rehabilitative therapy works.

 

Speaking of these authors, I recently (while searching for something else) came across this Canadian Institute of Health Research grant award from 2022 also with Busse & Zeraatkar as PIs. Don't think their intention to do this was mentioned on the forum before:

 

Something that is notable from this is the paucity of trials assessing PEM in LC. Searching the supplementary data & the spreadsheet on osf.io I think there is only one included trial where PEM was assessed as an outcome measure (?), a trial of leronlimab (Gaylis, 2022), although the authors also mention that the REGAIN triallists monitored patients for PEM but did not report any instances of it.

The commentary below was particularly annoying - anyone think it might be useful to put together a BMJ rapid response addressing it?

 

This is likely the future paper Garner was referring to on the BBC radio segment.

 

https://www.sciencemediacentre.org/...abilitation-for-the-management-of-long-covid/

 

Press release:
NEWS RELEASE
27-NOV-2024
Talking therapy and rehabilitation probably improve long covid symptoms, but effects modest
And no compelling evidence for other interventions including certain drugs, dietary supplements, inspiratory (breathing) muscle training or oxygen therapy
Peer-Reviewed Publication
BMJ GROUP
https://www.eurekalert.org/news-releases/1066181

 

and yet

Amygdala and Insula Retraining Tied to Reduction in Fatigue With Long COVIDAmygdala and Insula Retraining Tied to Reduction in Fatigue With Long COVID

thread on research paper here Trial Report - Neuroplasticity Intervention, Amygdala and Insula Retraining (AIR), Significantly Improves Overall Health ..., 2024, Bratty | Science for ME

PG Paul Garner: on his recovery from long covid - The BMJ

eta:
so not brain retraining then, just back to the CBT,GET 'therapy'.....
definitely not Carlsberg.

 

"I suddenly believed I would recover completely" and avoiding pwME experiences is what he thinks saved him.

 

I hope some people will. I’m afraid I’m not up to it at the moment.

 

Eric Topol shared it on Twitter saying:

A systematic review of 24 randomized trials for #LongCovid https://bmj.com/content/387/bmj-2024-081318 open-access @bmj_latest
No drug, diet, or device intervention has supportive evidence for efficacy. CBT, rehab provided some relief of symptoms (moderate certainty). We're still in desperate need for a validated treatment!

Danny Altmann just retweeted Topol with the following comment:

Hi @EricTopol
- it was noteworthy that coverage somehow latched onto CBT and rehab sometimes being better than nothing. Surely the real take-home was that >4y on, we have nothing substantive to offer some 400 million people globally. We should be able to do better than this..

 

This is all based on the 1 Dutch trial by Hans Knoop (Kuut et al. 2023, discussed here). A study on COPD patients found the minimal importance difference for the CIS-fatigue scale to be 9.3 points, so bigger than the 8.4 difference found in the CBT trial. The reviewers rated the Kuut 2023 study at high risk of bias because of lack of blinding but this resulted in only 1 downgrading in GRADE hierarchy from high to moderate certainty of evidence.

Curiously, the RCT on hyperbaric oxygen therapy also reported positive effects but here the evidence was downgraded by two levels (from High to Low) 'due to very serious imprecision' even though for some outcomes the 95% confidence intervals do not cross 0.

This all seems to be based on 1 trial on 'People who were still suffering from breathlessness three months after being discharged from hospital with COVID-19-related acute respiratory distress syndrome.'
https://pubmed.ncbi.nlm.nih.gov/37271020/
EDIT: It seems to be the REGAIN trial that we has was discussed here:
https://www.s4me.info/threads/clini...9-condition-regain-study-2024-mcgregor.37174/

This compares 2 forms of exercise, so provides no evidence that exercise is helpful or not.

 

I gather this paper was being discussed on the BBC Today programme this morning but I’ve not listened yet.

 

https://twitter.com/user/status/1862198291661820328