20 juli 2022:  Bron: AD en  2022; 12: 11252

Mensen die langdurige klachten hebben overgehouden aan een coronabesmetting (Covid-19) kunnen baat hebben bij een hyperbare zuurstof behandeling, zo blijkt uit een Israelische studie. Centra voor hyperbare zuurstoftherapie in Nedserland gaan patiënten met Long Covid deze behandeling aanbieden op basis van de resultaten uit de Israelische studie
In vergelijking met de placebogroep verbeterden bij de long covidpatienten vooral de tijd in de globale cognitieve functie, aandacht en executieve functie (respectievelijk d = 0.495, p = 0.038; d = 0.477, p = 0.04 en d = 0.463, p = 0.05). Significante verbetering werd ook aangetoond in het energiedomein (d = 0.522, p = 0.029), slaap (d = −0.48, p = 0.042), psychiatrische symptomen (d = 0.636, p = 0.008) en pijninterferentie (d = 0.737 , p = 0,001).

Grafieken uit het studierapport zie  Table2,2, en Supplementary Table 3)

Het Algemeen Dagblad heeft een kort interview met de directeur van het hyperbare zuurstof Centrum in Goes. Naar aanleiding van deze studie gaan zij dit aanbieden aan patiënten met Long Covid:

Hyperbaar centrum in Goes gaat patiënten met long covid behandelen na veelbelovend onderzoek

GOES - Mensen die langdurige klachten hebben overgehouden aan een coronabesmetting, kunnen binnenkort waarschijnlijk voor behandeling terecht in het Centrum voor Hyperbare Zuurstoftherapie in Goes.


Dat zegt directeur Maarten van Tol op basis van veelbelovende onderzoeksresultaten uit Israël. Long covid-patiënten hebben vaak verschillende klachten, waaronder vermoeidheid, concentratieproblemen, kortademigheid, hoofdpijn en/of hartkloppingen. Soms kampen ze met depressie of vergeetachtigheid. Uit een uitgebreid onderzoek dat is uitgevoerd door een medisch centrum en de universiteit van Tel Aviv is gebleken dat deze mensen baat kunnen hebben bij hyperbare zuurstoftherapie. Daarbij wordt door inademing van honderd procent zuurstof onder verhoogde druk 12 keer meer zuurstof dan normaal opgenomen in de bloedbaan. Hierdoor kunnen weefsels die een tekort aan zuurstof hebben weer herstellen. De therapie wordt al ingezet om bijvoorbeeld chronische wonden sneller te laten genezen en klachten naar aanleiding van bestraling of pijnklachten te laten afnemen.>>>>>>>lees verder

Het studierapport zelf is gratis te lezen of te downloaden. Hier het abstract van de studie. Klik op de titel van het abstract:

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.

Discussion

This is the first prospective, randomized sham-controlled trial demonstrating significant improvement beyond the expected clinical recovery course of post-COVID-19 condition. We found that HBOT improves dysexecutive functions, psychiatric symptoms (depression, anxiety and somatization), pain interference symptoms and fatigue. Those changes were associated with increased CBF and brain microstructural changes in frontal, parietal and limbic regions associated with cognitive and psychiatric roles.

Becker et al. show that the main cognitive impairments in post-COVID-19 condition is dysexecutive, or brain fog, with considerable implications for occupational, psychological, and functional outcomes. In this study, improvements in the memory domain was in both groups, which can be attributed to the natural course of the disease. However, executive function and attention improved only following HBOT. A previous study has demonstrated decreases in CBF in frontal and temporal cortices of post-COVID-19 patients. Hence, the improvement following HBOT may be attributed to the increases in CBF and MD, demonstrated in the BA10, BA8 and BA6 areas that are associated with executive function and attention.

Post-COVID-19 condition is associated with long term psychiatric symptoms including depression, anxiety, and somatization,. HBOT improved both depression and somatization symptoms. Benedetti et al. detected robust associations between anxiety and depression in post-COVID-19 patients, and DTI measures of GM and WM microstructure in the superior and posterior corona radiata, superior longitudinal fasciculus and cingulum. In this study, the psychiatric improvement was also associated microstructure changes in the superior corona radiata area. Furthermore, we previously studied childhood abuse induced fibromyalgia patients in whom HBOT induced significant metabolic improvements in the same brain areas in addition to similar clinical improvement in somatization and depression. The association between improvements in the psychiatric symptoms to the MRI changes gives further strength to the biological nature of this disease and HBOT’s effect.

HBOT also improved pain interference. Interestingly, the pain interference score was high at baseline in both groups whereas the severity score was not. Diffuse muscle and joint pain without local inflammation or malformation is one of the common symptoms of post-COVID-19, resembling other central sensitization syndromes, such as fibromyalgia. A growing number of clinical studies, have demonstrated the efficacy of HBOT in improving pain and quality of life of fibromyalgia patients,,. Previous studies have shown that fibromyalgia is associated with decreased brain perfusion in the insula, hippocampus, putamen, prefrontal and cingulate cortex. In the current study, these regions showed increased perfusion after HBOT.

In post-COVID-19 condition, fatigue is a common symptom, and this symptom was reported in 77% of the study’s patients. HBOT improved both physical limitations and the energy domains. In concordance, Robbins et al. reported a significant improvement in fatigue following HBOT sessions in post-COVID-19 patients. The HBOT induced MD changes in the frontal lobe (BA 6,8,10) can be associated with the clinical results, as hypometabolism in the frontal lobe has been implicated with fatigue in COVID-19 patients. Post-COVID-19 fatigue has many overlaps with chronic fatigue syndrome (CFS). Symptoms common to CFS and post-COVID-19 condition include fatigue, pain, neurocognitive/psychiatric symptoms, reduced daily activity, and post-exertional malaise. Previous studies have demonstrated the efficacy of HBOT in CFS, in reducing symptom severity and increasing quality of life,.

The pathogenesis of post-COVID-19 condition in the central nervous system includes direct neuronal injury in the frontal lobes, chronic injury mediated by glial cells, ischemic events mediated by thrombotic events, mitochondrial dysfunction, and chronic inflammation. Growing evidence shows that new HBOT protocols can induce neuroplasticity and improve brain function even months to years after the acute injury,. These protocols, including the one used in the current study, utilize the so called “hyperoxic-hypoxic paradox”, by which repeated fluctuation in both pressure and oxygen concentrations induce gene expression and metabolic pathways that are essential for regeneration without the hazardous hypoxia. These pathways can modulate the immune system, promote angiogenesis, restore mitochondrial function and induce neurogenesis in injured brain tissue. Some or all of these effects may explain the beneficial effects found in the current study.

The primary strength of this study is the sham protocol which was found effective in blinding participants to treatment. Although this study presents advanced imaging methods, and whole brain study approach, which were correlated with clinical findings, the study has several limitations. The sample size is relatively small. Larger cohort studies may identify patients who can benefit the most from the treatment. The HBOT protocol included 40 sessions. However, an optimal number of sessions for maximal therapeutic effect has yet to be determined. Lastly, results were collected 1–3 weeks after the last HBOT session, and long-term results remain to be collected.

In conclusion, HBOT can improve dysexecutive functions, psychiatric symptoms (depression, anxiety and somatization), pain interference symptoms and fatigue of patients suffering from post-COVID-19 condition. The beneficial effect can be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles. Further studies are needed to optimize patient selection and to evaluate long-term outcomes.

Supplementary Information

Acknowledgements

We would like to acknowledge Oshra Meir Genuth, Hila Goldner Yerushalmi, Roy Sagi, Eli Matalon, Natalya Tarasula, Moran Adler, Ron-El Goldman, Eldad Yaakobi, Fanny Atar, Rotem Barti, Yonatan Zemel and Yair Bechor for their dedicated work. We would also like to thank Dr. Mechael Kanovsky for his editing of this manuscript.

Author contributions

S.Z.I., M.C., K.E.S., A.H., S.E. conceived and designed the study. S.Z.I., K.E.S., E.L., S.F., N.P., G.F., C.K., S.E. contributed to patients’ recruitment and data acquisition. M.C., A.H., E.S., Y.P., S.E. performed the data analysis. M.C., E.S. and A.H. performed the statistical analysis, M.C., S.Z.I., A.H., S.E. wrote the first draft of the manuscript. All authors revised and finalized the manuscript.

Funding

The study was funded by the research fund of Shamir Medical center, Israel.

Data availability

The datasets analyzed during the current study available from the corresponding author on reasonable request.

Competing interests

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.

Footnotes

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

These authors contributed equally: Shani Zilberman-Itskovich and Merav Catalogna.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-022-15565-0.

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