Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial

Abstract

IntroductionLong COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL.Methods and analysisA randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board.Ethics and disseminationThe trial is approved by the Swedish National Institutional Review Board (2021–02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access.Trial registration numberNCT04842448.

Effects of Hyperbaric Oxygen Therapy on Long COVID: A Systematic Review

“…In 2022, Kjellberg et al [27] reported a protocol for a phase II, randomized, placebocontrolled, double-blind clinical trial. This study aimed to explore the potential of HBOT in enhancing the health-related quality of life (HRQoL) in long COVID patients.…”

COVID-19 and abnormal uterine bleeding: potential associations and mechanisms

“…This study was small and had no control group. A small ( n =73) randomised, placebo-controlled, double-blind trial has also shown benefits of daily HBOT [ 115 ] and a phase II clinical trial is in progress [ 116 ]. During HBOT, the arterial O 2 tension typically exceeds 1500 mmHg, and levels of 200–400 mmHg occur in tissues [ 117 ], consistent with it having an impact on endometrial tissue oxygen levels.…”

Postural orthostatic tachycardia syndrome and other related dysautonomic disorders after SARS-CoV-2 infection and after COVID-19 messenger RNA vaccination

“…One patient has been reported under treatment with enhanced external counterpulsation ( 100 ). Cognitive behavioral therapy ( 101 , 102 ), breath retraining, and paced postural exercises incorporating breathing, such as yoga and hyperbaric oxygen, have been proposed ( 103 – 105 ). The increased demand for autonomic specialists and clinics since the start of the COVID-19 pandemic reveals the need for more resources to adequately care for this patient population ( 106 ).…”