Candidate treatments for long COVID: a narrative review of expert and patient-driven priorities, 2026, Baptista, Glasziou+

[SNT Gatchaman]

Candidate treatments for long COVID: a narrative review of expert and patient-driven priorities

Spoiler: Authors

Baptista, Shaira Nicole; Atkins, Tiffany; Chakraborty, Samantha; Bakhit, Mina; Glasziou, Paul; Byambasuren, Oyungerel

OBJECTIVE
To map the existing evidence for candidate treatments for long COVID that were prioritised by clinicians and people with lived experience, and to characterise their feasibility, acceptability and safety.

STUDY DESIGN
The study was conducted as a narrative review using pragmatic methods including iterative stakeholder-informed decision-making a monthly-updated evidence search, rapid lay evidence summaries and a structured research prioritisation process.

DATA SOURCES
Potential candidate treatments were identified via a combination of database and trial registry searches. These were then ranked by clinicians and people with lived experience using surveys. Evidence summaries for the top 14 interventions (low-dose naltrexone, antivirals, metformin, nicotine, vagus nerve stimulation, antihistamines, guanfacine, colchicine, nattokinase, intravenous immunoglobulins, monoclonal antibodies, coenzyme Q10, multicomponent rehabilitation packages, and exercise training) were created. Prioritised treatments were collated first by searching a collaborative living evidence database (updated monthly) of relevant systematic reviews and randomised controlled trials and then by conducting supplementary searches of other study designs.

DATA SYNTHESIS
Six of 14 interventions had long-COVID-specific randomised controlled trial (RCT) evidence (exercise [16 RCTs], multicomponent packages [5 RCTs], coenzyme Q10 [2 RCTs], antivirals [1 RCT], vagus nerve stimulation [1 pilot RCT], monoclonal antibodies [1 small RCT]); the remainder relied on indirect or very low-certainty data (e.g., uncontrolled studies or mechanistic rationale). Across interventions, evidence certainty was mostly low to very low, and safety/feasibility varied.

CONCLUSION
This review prioritises and maps candidate treatments for long COVID. There was insufficient direct evidence to inform clinical recommendations. Rather, the treatments presented in this review represent those that could be rigorously tested in clinical trials as they show biological plausibility and/or are feasible and acceptable to people with lived experience and clinicians.

REGISTRATION
A review protocol was not prospectively registered because the review adopted an iterative approach to support priority setting rather than clinical guidance.

Web | DOI | PDF | Frontiers in Medicine | Open Access

 

[SNT Gatchaman]

Exercise training — High quality evidence — 16 RCTs — Effectiveness: possible benefit — Safety: quite safe especially if supervised

While individualised, symptom-titrated and supervised programs, appear to be more effective, some authors highlight the challenges associated with implementing exercise interventions within this population. For example, post-exertional malaise which involves a worsening of symptoms following physical exertion can be a major barrier for people with long COVID. Exercise is considered to be generally safe, accessible, and low-cost, with most forms easily performed at home and a low risk of adverse events when properly supervised.

Although some treatments such as exercise training show promise and seem feasible and acceptable, there is insufficient high-quality evidence to make informed recommendations for clinicians and people living with long COVID. For funders, researchers and other stakeholders, this review highlights critical evidence gaps, including the need for randomised clinical trials that investigate treatments that are acceptable to and aligned with lived experience.

In this review, we summarised the evidence for, acceptability, feasibility and safety for 14 stakeholder-prioritised treatments for long COVID. Only six of these have any RCT evidence and most are supported by limited or indirect data. The next step is well-designed trials that use standardised patient centered outcomes, ensure adequate follow-up and consider implementation. This review supports the development of such trials rather than providing guidance in clinical settings.

 

[forestglip]

Fourteen intervention summaries were created based on the prioritisation process. Table 1 summarises each of these while Appendix 1 in Supplementary material contains each included evidence summary in detail.

None of the details of the exercise trials are in the paper, so I wanted to check the supplementary material, but I can't find Appendix 1. I see a file called "Supplementary file 1.docx" which includes "Appendix A: Search terms for the living database", but it doesn't seem to have Appendix 1.

 

[Utsikt]

This is the first exercise trial they list:

https://www.s4me.info/threads/clinical-effectiveness-of-an-online-group-physical-mental-health-rehab-programme-for-post-covid-19-condition-regain-study-2024-mcgregor.37174/

It’s unblinded and uses subjective outcomes.

 

[Trish]

With Glasziou involved, of course they were going to claim exercise is beneficial with no evidence of harm. He doesn't understand PEM, but that hasn't stopped him.

 

[rvallee]

Although some treatments such as exercise training show promise and seem feasible and acceptable, there is insufficient high-quality evidence to make informed recommendations for clinicians and people living with long COVID. For funders, researchers and other stakeholders, this review highlights critical evidence gaps, including the need for randomised clinical trials that investigate treatments that are acceptable to and aligned with lived experience.

If 16 isn't enough, why would 17 be? Or 25? Do we stop at 100? 200? There have already been way more than 16, but most of them are such garbage they aren't even worth reviewing by people who badly want it to be true. That fact alone is damning. Having this little to show for it after all this time is completely pathetic. This entire approach is a useless nightmare. Drugs don't go through a dozen pilot clinical trials, this is not a thing. And drug trials are already a giant pitfall where false results are common.

The next step is well-designed trials that use standardised patient centered outcomes, ensure adequate follow-up and consider implementation.

What would be the "No true Scotsman" equivalent here? There is always a call for "well-designed" research, but none of them ever are, because a well-designed trial would show it's worthless. Good grief.

Also I don't know how the hell a "multicomponent packages" makes sense to anyone but whatever, with someone like Glasziou it was always going to end up with the traditional conclusion.

 

[EndME]

It is rather amusing that they don't differentiate between RCTS and DBRCTS, as if randomisation is the most crucial part... I guess we don't need placebo-controlled trials anymore?

 

[EndME]

I have to have a closer look but as far as I can tell it seems they again missed out on treatments which according to their own ranking would be good candidates (such as HBOT, which likely does nothing but has had multiple positive RCTs).

 

[Sean]

Paul Glasziou

Well that's a bust from the start.

Across interventions, evidence certainty was mostly low to very low, and safety/feasibility varied.​

Yet that has never stopped him from recommending exercise before.

It is rather amusing that they don't differentiate between RCTS and DBRCTS, as if randomisation is the most crucial part... I guess we don't need placebo-controlled trials anymore?

Randomisation is sufficient control is the deceit upon which the entire psychosomatic empire is built.

It is no such thing, of course. It is just one of the necessary means to implement control, but nowhere near sufficient on its own. In the same way as statistical power, well characterised patient group, etc. All of these are required for a robust properly controlled study. Including most certainly either double blind placebo or objective outcome measures, or both.