Hyperbaric oxygen therapy improves neurocognitive functions & symptoms of post-COVID condition: randomized controlled trial, 2022, Zilberman-Itskovich

Abstract


Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection.

Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1–3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = − 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001).

Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT’s beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

https://www.nature.com/articles/s41598-022-15565-0

 

From Dr Herbert Renz-Polster (member of the scientific advisory board of the Deutsche Gesellschaft fur ME/CFS):

“First RCT on HBOT in #LongCovid

I am unimpressed. If you do 40 HBOT sessions you want to have larger effects. If you deduct the improvements also seen in the sham group , the HBOT patients rarely improved by > 10 points in the (100 point) SF-36 domains.”

https://twitter.com/user/status/1547636471003197444

 

A question on statistics. The authors wrote:

Considering that the primary outcome was an evalution of 6 neurocognitive domains, shouldn’t it rather be 0.05 / 6 = 0.0083?

As for the secondary outcomes, considering that 22 domains were compared (across 4 questionnaires), shouldn’t it be 0.05 / 22 = 0.0023?

Or should it be the sum of all comparisons across both primary and secondary outcomes, i.e. 0.05 / (6 + 22) = 0.0018?

Edit: the authors seem to have applied Bonferroni correction to within-group pre-post intervention (HBOT or sham) comparisons of subdomain scores, but not to their ANOVA model. Should they have?

 

So...

What is a sham HBOT treatment? You simply sit in the chamber and it doesn't get pressurized, for 40 sessions on end? yes. 90 minutes per treatment, 5 days a week.

These are big claims:

Lastly this caught my attention:

 

Lost me there. This is so much like in a cult where the doctrine always has to be injected into any discussion.

The obsession with neuroplasticity is destroying more brain function than literally all the alcohol in the world. It's like concentrated Humours, except all the other organs have been eliminated from the list so every unknown is attributed to some magical brain function somewhere. What a dumb era in medicine, even worse by comparison to the Humours because of how late it's happening.

 

Leonid Schneider (data sleuth & scientific integrity journalist) has flagged this study because the authors have previously been involved in scientific fraud. The owner of the company, Dr Schai Efrati, has previously made claims that HBOT is an effective treatment for many conditions.

Importantly, Schneider spotted that 11% of the patients in the intervention group had been hospitalized for Covid while that number rose to 22% in the control group.

The study has also been retweeted by Peter McCullough, a notable anti-vax cardiologist.

https://forbetterscience.com/2022/07/15/schneider-shorts-15-07-2022-how-to-swear-in-french/#hbot

 

Just to play devil's advocate... do we expect any doctors or scientists who *aren't* already interested or invested in Hyperbaric to spend the time and money to study it?

Anyway, valid critiques aside, it's kinda cool that they successfully blinded this trial. Almost like this listened to this guy from last year: https://www.s4me.info/threads/hyper...vention-2021-robbins-et-al.23750/#post-396804

 

There is a doctor here, owner of a private clinic for HBOT, who has been popping up in the media recently, promoting HBOT as a treatment for long covid. (Interestingly, she is a psychiatrist originally.) To prove her point, she says there have been double-blinded placebo controlled studies that show this works for LC, so I guess this study is what she meant. Not very convincing then.

 

Followed up with Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial (2024, Nature Scientific Reports)

 

Straight in at 2ATM? MS HBOT centres ease people in at 1.5ATM (equivalent to 16 feet depth) for 20 sessions minimum. Then you can choose to go to 24ft, then 33ft which is 2ATM. I tolerated 1.5ATM well but 1.75ATM set me back. Possible oxidative stress? I would be very worried if LC patients started on 2ATM HBOT if they had developed ME in the meantime.
In MS there is little evidence for HBOT being effective. MS patients cannot even access home surface oxygen.

 

The paper spends half its time discussing hypoxic-ischaemic encephalopathy in neonates, with experiments in 7-day old rats. Then goes on to focal and global cerebral ischaemia.

In summary figure 6 is —

Fig. 6. Mechanisms of HBO neuroprotection. Cerebral hypoxia–ischemia disables energy metabolism, reduces ATP production, releases glutamate, and causes calcium overload and depolarization. Mitochondrial damage follows, with oxygen radical generation and inflammatory reactions. All these pathological events not only lead to apoptotic neuron death, but also result in brain infarction, brain edema and the dysfunction of blood–brain barrier. The final outcome is the death or disability of patients. HBO either improves oxygen delivery or oxygen extraction to enhance neuronal viability. HBO protects the blood–brain barrier and reduces cerebral edema. Cerebral metabolism is improved by HBO and levels of glutamate, glucose, and pyruvate are stabilized. The inhibitory effect of HBO on inflammatory agents and on apoptosis may be mediated by the re-regulation of superoxide dismutase and by enhancing the expression of pro-survival Bcl-2 genes. Finally, HBO decreases the deformability of the red blood cells to improve microcirculation and reduce hypoxia–ischemia.​

The legend says HBO decreases the deformability of the red blood cells, but they mean increases, as in the graphic. Blood and oxygen needs to get to the brain but also blood flow needs to clear neurotoxic waste-products of metabolism. RBC deformability will help the microcirculation but is probably not fully compensating.