Effect of normobaric and hyperbaric hyperoxia treatment on symptoms and cognitive capacities in Long COVID patients: a randomised placebo-controlled, prospective, double-blind trial.

Abstract

Introduction: Long COVID syndrome is a major health issue. Multiple treatments have been proposed but efficacy is inadequately investigated. Hyperbaric oxygen therapy (HBOT) has been promoted based on a small number of publications. As there is potential for a placebo effect and the financial cost of HBOT is high, we sought to investigate the effects of HBOT in Long COVID in a randomised trial.

Methods: We randomised 101 patients into four treatment groups, receiving 10 sessions of oxygen 'treatment' inside a pressure chamber, according to one of four modalities: A - 100% oxygen at 253 kPa (2.5 atmospheres absolute); B - 40% oxygen at 253 kPa; C - 100% oxygen at 101.3 kPa (1 atmosphere absolute); D - 21% oxygen at 101.3 kPa. Groups B and C thus received a similar effective oxygen dose of 101.3 kPa. Quality of life symptom scores (Visual Analogue Scale; EQ-5D-5L, C19-YRSm), a 6-minute walking test and five neurocognitive tests were administered before and after the treatment series. At three months post-treatment, a telephone questionnaire probed for lasting effects.

Results: All groups were comparable with regards to demographics, Long COVID symptoms and severity. After treatment, there were no significant differences in subjective symptoms, functional scores, and cognitive performance between any groups. The response to treatment was highly variable, with some patients in even the 'placebo' group D reporting a significant improvement in their well-being. This was not reflected in any objective outcome scores. No subgroups of patients responded better to any of the treatments.

Conclusions: There was no significant effect from different doses of oxygen in a hyperbaric chamber. It is possible that the very modest improvements reported in other studies were due to a placebo effect. Claims that HBOT has a significant effect on Long COVID need further investigation before indiscriminately prescribing or promoting HBOT.