In case you missed it, HBOT is the most proven treatment for Long COVID

glenn_chan · June 25, 2023, 7:56pm

The most reliable scientific evidence comes from double-blind randomized controlled studies. There have only been a handful of those for Long COVID or similar conditions:

Hyperbaric oxygen therapy (HBOT)
Leronlimab, a CCR antagonist
AXA1125
Phyto-V (RCT link)
IVIG for post-polio syndrome (and other conditions), which may be unrelated to Long COVID
Rituximab for ME/CFS, which should be more like Long COVID than post-polio syndrome

Links to the RCTs can be found at the List of doctors and approaches - Long Haul Wiki

Phyto-V - why I don’t trust the published science on this Phytochemical capsuleOf the RCTs listed above, only 2 of them had positive statistically significant results. I won’t talk about Phyto-V here because it probably needs its own post. The Phyto-V data may be unreliable because Robert Thomas has potential conflicts of interest with keep-healthy.com. So that leaves us with HBOT…

The Shamir Medical Center RCT

Shamir Medical Center in Israel funded a randomized controlled trial of HBOT on Long COVID patients. It compared HBOT at 2ATA (with oxygen) to ‘sham’ HBOT that was as mild as possible to give the impression of HBOT treatment. Both the high-pressure HBOT group and the ‘sham’ control group experienced a few cases of barotrauma. The blinding was fairly good as “the correct group allocation perception rate was 54.1% and 66.7% (p=0.271) in the HBOT and control groups respectively”.

One strength of the trial was that endpoints were pre-registered (NCT04647656) to ensure that the results are reliable and free of data mining. The trial met its primary endpoint of cognitive improvement as measured by Neurotrax, a computerized set of tests that objectively measures cognitive performance.

How to get more information: The study results paper can be found at Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial | Scientific Reports

Safety considerations with HBOT

For some reason, a few people seem to react very badly to HBOT on the first session or within the first few sessions. This seems to happen even at lower pressures.

One anecdote: Veronica Smith reported worsening after 9 sessions at 1.5 (?and 2?) ATA. Negative symptoms became clearer following dives 4 and 5.

Here’s survey data showing the same idea. The rate of mild and significant worsening is roughly the same between low and high pressure HBOT.

To save some money, you can start with lower pressures to see if you will react and to reduce your exposure to HBOT. Lower pressures = less HBOT. A Swedish study provided ~1.18 ATA HBOT to its sham group, which experience adverse events similar to the treatment group (which got HBOT at much higher pressure).

Oxygen toxicity

An animal study found that excessive HBOT can lead to death in lab animals. See Warren et al. (DOI:10.4049/jimmunol.121.1.315). Human patients also report the same thing. So after 10-40 sessions, you may want to start paying attention to whether or not HBOT is making your symptoms worse rather than better.

Fire hazard

One of the ways to try to save money/time is to buy a soft shell chamber and to sleep in it (so that it doesn’t take “time” to do your HBOT). You would be sleeping in a fire hazard because oxygen and pressure makes fire burn faster.

So… you really need to know what you’re doing if you try something like that.

Herx reactions

If you have Lyme or spirochete bacteria dying off, you may experience serious side effects. However, if you can confirm that a Herx reaction is happening (e.g. previous similar reaction with antibiotics), it may be worthwhile to use HBOT to slowly kill off bacteria under competent medical supervision. Horowitz is a Lyme doctor who explains Herx reactions in this video.

However, be careful about doctors who have a financial incentive to mis-diagnose you with a Herx reaction. There are some bad doctors who will try to hide their mistakes/ignorance/grift by blaming bad outcomes on a “Herx” reaction - see the thread on it.

Cost

Only a small portion of people seem to really benefit from HBOT- there’s some additional data here in the ‘what worked’ video. If you aren’t noticing results within the first several session of high-pressure HBOT, then you don’t need to throw your money down a pit.

If you scroll up to the charts, you can see that most people don’t report significant improvement. It also turns out that the survey data is optimistically biased so people will report slightly improvement for treatments that may be doing nothing.

High pressure versus low pressure

Unfortunately, the higher pressure HBOT seems to be delivering more benefit than lower pressure HBOT. It is a lot more expensive. Whereas you can spend several thousand dollars to $15K to buy a soft shell chamber, buying a hard shell chamber capable of higher pressures is not so straightforward.

I don’t know if you can make that up by doing a lot of low-pressure HBOT. I just haven’t seen data on that yet.

The UK

The UK has a series of charities that provide HBOT at a lower cost.

The bottom line

While cost will be a barrier for some people, this is the most proven treatment for Long COVID. Hopefully other treatments will have high-quality studies supporting their use so that other treatments involves less guesswork and dice rolling. I certainly don’t think that HBOT is the only treatment you should look at, especially because most people won’t respond to it.

glenn_chan · December 27, 2023, 10:33pm

Anecdotes of long-lasting worsening

u/TheAnimal777:

After that 10th day I never went again, but every night since I’ve been waking up at 3 or 4 am with massive adrenaline dumps. It basically feels like my fight or flight is on overdrive and I’ll wake up feeling like adrenaline, fear, and stress is pumping through my body, especially heart (sort of like hyper-adrenal dysautonomia). I’m usually unable to fall back asleep and it’s been pretty awful.
https://www.reddit.com/r/covidlonghaulers/comments/18rr8bi/hyperbaric_oxygen_therapy_caused_debilitating/

Agy_lena (ME/CFS):

HBOT for example. That made me permanently worse.
https://twitter.com/agy_lena/status/1538196144634875904

Veronica Smith reported worsening after 9 sessions at 1.5 (?and 2?) ATA. Negative symptoms became clearer following dives 4 and 5.

Somebody I know paid for 40 sessions but never went back after the first sessin.

glenn_chan · January 17, 2024, 5:04pm

Some colour on the conflicts of interest with the RCT involving Shai Efrati:

Shai Efrati is a shareholder in Aviv Scientific as well as an employee of the Sagol Centre whose whole goal it is to roll out a very wide network of HBOT clinics all over the world.

In their first paper they still declared a conflict of interest Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial | Scientific Reports, “Amir Hadanny and Efrat Sasson work for AVIV Scientific LTD. Shai Efrati is a shareholder at AVIV Scientific LTD. LTD. SZI, MC, KES, EL, SF, NP, GF, CK, RS, YP, MS have no competing interests.”

“Aviv Scientific is a leader in research on age-related cognitive and functional decline and novel applications of hyperbaric medicine to maximize human performance. Aviv focuses on improving the aging process by increasing cognitive and physical performance in healthy aging adults. Based on an exclusive global partnership with the world’s largest Hyperbaric medicine and research facility, the Sagol Center at Shamir Medical Center in Israel, Aviv Scientific is rolling out a global network of medical clinics focused on the enhancement of cognitive and physical performance with hyperbaric medicine and related technologies at its core. “ Improving Cognitive and Physical Decline | Aviv Scientific

In subsequent papers they don’t declare any conflict of interest anymore see for example The effect of hyperbaric oxygen therapy on myocardial function in post-COVID-19 syndrome patients: a randomized controlled trial | Scientific Reports “The authors declare no competing interests.”

If you read the studies on HBOT you will see that they are not very convincing. After all they aren’t LC researchers but simply HBOT researchers that apply HBOT to anything, which is fair enough.

from https://www.reddit.com/r/covidlonghaulers/comments/15mmeln/comment/kianaid/?utm_source=reddit&utm_medium=web2x&context=3

glenn_chan · February 16, 2024, 10:40pm

The people who ran the Shamir Medical Center RCT are claiming that the benefits stick around after a year. Here’s their updated paper.

The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session.

glenn_chan · March 13, 2024, 4:33pm

The Aviv clinics guy throwing shade at competing HBOT… not great for patients

Shai Efrati was one of the key people behind the HBOT RCT. He is clearly affiliated with Aviv clinics (which sells high pressure HBOT) but he no longer discloses that conflict of interest in his papers.

In an interview on the Aviv clinics Youtube channel, he talks describes high pressure HBOT as “very safe”, which is not how I would characterize HBOT.

51:47 Be evaluated by a professional. He will evaluate you and once he will say that you are suitable then the treatment is generally very safe.

The survey data does show that some patients do respond very negatively to HBOT. Here’s some data from the latest Patient Experiences Survey (TOS data was shown earlier in this thread).

And as mentioned earlier, oxygen toxicity can be an issue.

One problem with getting “professional” medical advice from a HBOT clinic is that they have an incentive to sell you HBOT. What we’ve seen in the US dialysis industry is that rates of in-clinic dialysis are higher in the US than Canada because only the US doctors are allowed to profit from steering their patients towards in-clinic dialysis. I would expect the conflict of interest in HBOT to cause some doctors to steer their patients towards too much HBOT. Perhaps they may even ignore HBOT treatment going the wrong way.

We also see Efrati show his bias towards competing HBOT - namely the soft shell HBOT chambers that he shows in his presentation.

42:56 many people are buying by Amazon or whatever it is and put them on the backyard this is not it don’t get into that this is not working it can be dangerous this is actually less than our placebo group if you need the treatment your health is important go to professional who knows what they are doing

“actually less than our placebo group” is saying that the soft shell chambers achieve lower pressures. Their placebo group received a brief spurt of 1.2 ATA.

To mask the controls, the chamber pressure was raised up to 1.2 ATA during the first five minutes of the session along with circulating air noise followed by decompression (0.4 m/min) to 1.03 ATA during the next five minutes.
Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial | Scientific Reports

However, this is an unfair dig on cheap HBOT chambers as many of them achieve pressures of 1.3, 1.4, and even 1.5 ATA.

His second dig on cheaper HBOT is that they are “dangerous” whereas his clinic’s HBOT is not. I would not characterize it that way… the data shows that both can cause harm to chronic illness patients. He has a clear bias towards what he is selling and that is not something that you want to see as a patient.

glenn_chan · April 29, 2024, 4:16am

Here’s one person’s thoughts on why they didn’t try HBOT. I don’t agree with most of it but a few of the points are good, e.g. three of the authors of one of the HBOT papers have conflicts of interest.

Evaluating HBOT for Long COVID

Liface · August 24, 2025, 10:54pm

Here’s a recent (April 2025) trial with a negative finding:

Participants Previously healthy subjects aged 18–60 years, diagnosed with long covid were included. We excluded pregnant women, patients with RAND-36 (role limitations due to physical health (RP) and physical functioning (PF)) above 70, diabetes, hypertension and contraindications for HBOT.

Interventions Subjects were randomly assigned to 10 sessions of HBOT or sham (placebo) treatments over 6 weeks. HBOT involved 100% oxygen, 2.4 bar, 90 min, placebo medical air, 1.34–1.2 bar. Randomisation (1:1) was done electronically, in blocks stratified by sex and disease severity. Subjects and investigators were blinded to allocation.

Primary and secondary outcome measures Primary endpoints were changes from baseline in RAND-36 PF and RP at 13 weeks. Efficacy was analysed on an intention-to-treat basis. Harms were evaluated according to the actual treatment given.

Results Between 15 September 2021 and 20 June 2023, 80 subjects (65 women, 15 men) were enrolled and randomised (40 in each group). The trial is completed. The primary endpoint analysis included 79 subjects (40 in HBOT and 39 in control). At 13 weeks, both groups showed improvement, with no significant difference between HBOT and placebo in PF (least square mean difference between groups (LSD), 0.63 (95% CI −7.04 to 8.29), p=0.87) and RP (LSD, 2.35 (95% CI −5.95 to 10.66), p=0.57). Harms: 43 adverse events (AEs), most commonly cough and chest pain/discomfort, occurred in 19 subjects (49%) of the HBOT group and 38 AEs in 18 subjects (44%) of the placebo group, one serious AE in HBOT and one death in the placebo group.

Conclusions 10 HBOT sessions did not show more short-term benefits than placebo for long covid patients. Both groups improved, with a notable sex difference. HBOT has a favourable harm profile.

Thought as to the high rating of HBOT on your patient survey: maybe people who tried HBOT were richer and thus had generally healthier lifestyles and were more likely to try other things or work harder to recover?

glenn_chan · August 25, 2025, 2:16am

Thanks so much for bringing that trial to my attention!

I don’t have information as to whether richer patients have better long-term outcomes. And I don’t know about ‘healthier lifestyles’.

As far as trying lots of treatments… that may actually hurt recovery (!!). See this thread (link below):

Liface · August 25, 2025, 2:39am

I don’t think that’s the conclusion we should be drawing from that data.

It makes perfect sense that people who recover do so quickly, before they have the opportunity to try lots of treatments. It’s probable they would have recovered just with pacing and time, without trying any treatments.

The hard cases, on the other hand, have to try lots of treatments.

Trying lots of treatments is not causal for being sick, rather, being sick is causal for trying lots of treatments.

glenn_chan · August 25, 2025, 6:53am

My thoughts on the Swedish HBOT study (Anders Kjellberg and colleagues)

Recap of the study results

Anders Kjellberg and his colleagues conducted a RCT on Long COVID patients (NCT04842448). The study compared high pressure HBOT at 2.4bar with 100% oxygen to a sham/‘placebo’ treatment (going from 1.34 to 1.2 bar HBOT; with placebo medical air).

Both the placebo (low pressure HBOT) group and treatment group improved over time.

While the treatment group had slightly higher improvement as measured by RAND-36 scores (for Physical Functioning and physical health), the difference was not statistically significant. A larger trial with 260 patients (130 in treatment and 130 in control) could, in theory, yield statistically significant results if there is an underlying benefit to HBOT.

The trial also measured patient outcomes via the 6 minute walk test, reactive hyperaemia index, 30-second chair-stand test, EQ-5D-5L index, and EQ-5D VAS. The results on these secondary endpoints was not statistically significant (see Table 2 in their paper). For all 5 secondary endpoints, the placebo group improved slightly more than the treatment group (!).

The results not being statistically significant; results conflict with the Israeli study

The sham treatment in the Israeli Shamir Medical Center study went from 1.2 to 1.03 ATA.
The sham treatment in the Swedish study went from 1.34 to 1.2 bar, which is ~1.32 ATA to ~1.18 ATA.

So, the Swedish sham treatment is vaguely similar to low pressure HBOT (which can be achieved with cheaper soft shell chambers). That could explain why the sham group in the Israeli study saw little improvement while the sham group in the Swedish study saw a lot of improvement.

That the sham group in the Swedish study got better is interesting. I always thought that low pressure HBOT does very little and that you need high pressure HBOT to get results (because that’s what my survey data indicated/suggested). I… don’t know what to think anymore.

If you dig a little deeper into the Swedish data, the secondary endpoints suggest that the sham group improved more than the treatment group (!). That result doesn’t make a lot of sense.

Placebo effect, low pressure HBOT doing work, or reporting biases?

The sham group actually did get better (on average). (There are probably people who got worse and many people in the sham group who discontinued treatment.)

I personally doubt that there’s a placebo effect in long COVID. The condition doesn’t look like IBS where hypnosis was a highly effective treatment in this RCT study. Long COVID doesn’t magically go away after meditation, acupuncture, trying lots of treatments, etc. etc.

The study could be measuring reporting biases. People answer questionnaires and surveys in weird ways. For example, some people will start ‘speedrunning’ surveys if it is very long or if they are subjected to an extensive amount of medical testing and questionnaires (the Swedish study did that). The subjects had to take the same survey 5 times. There’s weird-looking data such as the responder rates over time (as measured by the PF and RP portions of the RAND-36 questionnaire). For the HBOT group, it consistently went up according to PF - but it whipsawed around according to RP.

It may also be the case that low pressure HBOT does something. That would be very interesting if true because cost won’t be such a huge barrier.

The Swedish researchers’ thoughts

The paper talks about (theoretically) doing a study with more patients. It also talks about giving patients more HBOT, in line with the Israeli study. In the conclusion of the paper, the authors lean into the idea that they didn’t HBOT hard enough.

Further studies with subgroups for male and female populations and a dose of more than 10 sessions are required.

Safety of HBOT- both low and high pressure

In the Swedish study, 15% (6/39) in the HBOT treatment group discontinued while 7% of the sham group (3/41) discontinued. There was a severe adverse event in the treatment group and a suspected suicide in the sham group.

The paper nonetheless states:

HBOT delivered with medical grade oxygen and hospital standards of chamber safety seems safe for previously healthy patients with long covid.

The paper also acknowledges that the ‘sham’ treatment (when went from went from ~1.32 ATA to ~1.18 ATA) is sufficient stress for the patients to have a
physiological effect, which may explain the:

Unexpectedly small difference between active treatment and
sham treatment
The similarities in AEs

I would argue that both groups got at least a little bit of HBOT. Survey data on low-pressure HBOT suggests that low pressures are enough to cause patients to report negative experiences. It’s suggestive of low pressure HBOT doing work- good in some patients and bad in others.

The Swedish study paper discusses its safety findings versus the Israeli study:

Previously published RCT reported no significant difference in side effects between the groups (35.1% and 38.9%, p = 0.739 in the HBOT and control groups, respectively) and no discontinuation of the treatment due to side effects.10 Most previous trials with HBOT have not reported AEs in compliance with ICH-GCP.35 The similarities in AE occurrence between groups suggest that the AEs are not related to oxygen itself. Given the frailty of this group, it’s possible that AEs occurred in the placebo group due to the effort of participation, by breathing non-humidified air in sham treatment or would be observed in those subjects even without treatment. There is also a possibility that the sham treatment is sufficient stress for this group of patients to have a physiological effect, which may explain the unexpectedly small difference between active treatment and sham treatment, and the similarities in AEs. Alternative explanations for the higher rate of AEs are difference in disease severity, difference in treatment protocols (2.0 ATA vs 2.4 ATA) or differences in reporting of AEs. Our trial was conducted in compliance with ICH-GCP, which includes a meticulous reporting of AEs.

Disclosure / my bias

My bias is that I want HBOT to be helpful. If it isn’t, then patients just have to accept their crippling health problems and hope that they are among the people who are lucky enough to spontaneously recover.

Final thoughts

The results of this study are disappointing because we don’t have a clearcut answer as to whether or not HBOT is helpful.

If it is helpful, it is only helpful for a minority of patients. Response rates are low.

As far as finding effective treatment for Long COVID goes, here are my thoughts:

Measuring patient outcomes is hard. Studies can easily measure things that aren’t health outcomes.
Patients have tried almost everything.
If patients have found effective treatments, treatment response rates are very low (perhaps a few percent). This makes Long COVID expensive to study because we need big studies to find weak signals.
The endgame may be finding more treatments with very low response rates. We’re just going to have to find a lot of them.

It’s going to be a long road.

In other news, I consider myself fully recovered now (instead of mostly recovered)… and I’ve never done HBOT. The challenge is to figure out recovery for everybody… because copying what I did won’t work for the vast majority of people.

glenn_chan · September 1, 2025, 5:39pm

My hunch/intuition is that some patients may be unintentionally hindering their recovery by trying too many treatments. It is likely the case that treatments are more likely to cause more harm than good. That is the case for most of the experimental drugs that pharma tries.

If that wasn’t the case, then simply trying lots of treatments would improve the chances of recovery… which is the opposite of what the survey data suggests. (Of course, the problem is that surveys have difficulty with the difference between correlation and causation.)

Some (or most?) patients misreport(/misinterpret/misremember) outcomes

On average, there is a bias towards reporting positive outcomes rather than negative outcomes. IF there are more bad treatments than good treatments, then there is a reporting problem coming from some patients. They may be misreporting outcomes for various reasons.

There are also a few people who have a ‘everything works’ reporting style. Almost everything that they tried was reported as helping.

Implications

My concern is that some patients may be accidentally hurting their recovery by continuing to do treatments that are hurting them.

What I suggest is:

Try treatments one at a time. Then you’ll get a clearer picture of what that treatment does.
Slowly increase dosing. e.g. start with a 1/16th dose → 1/4th → normal dose.
Discontinue treatments that go the wrong way. Do not fall into the trap of detox or Herxheimer reactions.
? Avoid potentially risky treatments.

We need to place a big emphasis on safety. The information we get about this condition is far less reliable than initial appearances.

The scientific literature is unreliable and full of junk (like the rat with the giant balls that got past peer review).
Recovery stories and support group posts are biased.
Some patients seem to be misreporting outcomes.

We can easily get into trouble when we act on unreliable information. But if we prioritize safety, then we can be more robust against information being wrong.

I’m not happy that patients can’t simply follow in the footsteps of those who have recovered. But if we want to maximize the chances of recovery, then we have to be smarter about acting on unreliable information.