Is there a rationale for hyperbaric oxygen therapy in the patients with Post COVID syndrome? : A critical review

Abstract

The SARS-CoV-2 pandemic has resulted in 762 million infections worldwide from 2020 to date, of which approximately ten percent are suffering from the effects after infection in 2019 (COVID-19) [1, 40]. In Germany, it is now assumed that at least one million people suffer from post-COVID condition with long-term consequences. These have been previously reported in diseases like Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Symptoms show a changing variability and recent surveys in the COVID context indicate that 10-30 % of outpatients, 50 to 70% of hospitalised patients suffer from sequelae. Recent data suggest that only 13% of all ill people were completely free of symptoms after recovery [3, 9]. Current hypotheses consider chronic inflammation, mitochondrial dysfunction, latent viral persistence, autoimmunity, changes of the human microbiome or multilocular sequelae in various organ system after infection. Hyperbaric oxygen therapy (HBOT) is applied since 1957 for heart surgery, scuba dive accidents, CO intoxication, air embolisms and infections with anaerobic pathogens. Under hyperbaric pressure, oxygen is physically dissolved in the blood in higher concentrations and reaches levels four times higher than under normobaric oxygen application. Moreover, the alternation of hyperoxia and normoxia induces a variety of processes at the cellular level, which improves oxygen supply in areas of locoregional hypoxia. Numerous target gene effects on new vessel formation, anti-inflammatory and anti-oedematous effects have been demonstrated [74]. The provision of intermittently high, local oxygen concentrations increases repair and regeneration processes and normalises the predominance of hyperinflammation. At present time only one prospective, randomized and placebo-controlled study exists with positive effects on global cognitive function, attention and executive function, psychiatric symptoms and pain interference. In conclusion, up to this date HBO is the only scientifically proven treatment in a prospective randomized controlled trial to be effective for cognitive improvement, regeneration of brain network and improvement of cardiac function. HBOT may have not only theoretical but also potential impact on targets of current pathophysiology of Post COVID condition, which warrants further scientific studies in patients.

Keywords: Brain fog; COVID-19; Chronic fatigue syndrome; Hyperbaric oxygen therapy (HBOT); Hypoxia-inducible-factor-1; Long COVID; Post COVID condition; SARS-CoV-2.

Fig. 1

HBOT and it potential effects on different organs and tissues in Post-COVID syndrome

Fig. 2

Hyperoxia-hypoxia paradox and HIF. The alternation of phases of hyperoxia with phases of normoxia induces the formation of numerous signalling molecules that contribute to the formation of angioneogenesis, wound healing and reparative processes

Fig. 3

Monoplace and multiplace pressure chambers in use with patients. Monoplace pressure chambers can be operated with pure oxygen atmosphere as well as with ambient air. In the latter case, however, patients breathe oxygen through a mask in a closed system

Fig. 4

Oxygen concentrations through tissues. The signal transduction of HIF-1 for the detection of oxygen deficiency states in tissue. O₂ partial pressure in the tissue is shown

Fig. 5

Effect of repetitive HBOT on different cytokines and cell messenger molecules. Intermittent hyperoxia and normoxia is imitating effects of altitude training, which leads from normoxia to hypoxia in tissues

Fig. 6

HBO neurology regimen (TS 200/90) as used in the Long-COVID study from Israel [199]. The total pressures (200 kPasc) are shown. The total pressure remains below the wound regimen (TS 240/90), which is most commonly used as in diabetic foot syndrome and wound healing disorders