Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Apr 14;15(4):e094386.
doi: 10.1136/bmjopen-2024-094386.

Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid (HOT-LoCO): a randomised, placebo-controlled, double-blind, phase II trial

Anders Kjellberg  1   2 , Adrian Hassler  3 , Emil Boström  3 , Sara El Gharbi  3 , Sarah Al-Ezerjawi  3 , Anna Schening  2 , Katarina Fischer  4   5 , Jan H Kowalski  6 , Kenny A Rodriguez-Wallberg  7   8 , Judith Bruchfeld  4   9 , Marcus Ståhlberg  4   5 , Malin Nygren-Bonnier  10   11 , Michael Runold  12   13 , Peter Lindholm  14   15
Affiliations
Clinical Trial

Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid (HOT-LoCO): a randomised, placebo-controlled, double-blind, phase II trial

Anders Kjellberg et al. BMJ Open. .

Abstract

Objectives: To evaluate if 10 sessions of hyperbaric oxygen treatments (HBOTs) improve short- and long-term health related quality of life, symptoms and physical performance in long covid patients compared with placebo.

Design: Parallel, randomised, placebo-controlled, double-blind trial.

Setting: Single-centre, university hospital, Sweden.

Participants: Previously healthy subjects aged 18-60 years, diagnosed with long covid were included. We excluded pregnant women, patients with RAND-36 (role limitations due to physical health (RP) and physical functioning (PF)) above 70, diabetes, hypertension and contraindications for HBOT.

Interventions: Subjects were randomly assigned to 10 sessions of HBOT or sham (placebo) treatments over 6 weeks. HBOT involved 100% oxygen, 2.4 bar, 90 min, placebo medical air, 1.34-1.2 bar. Randomisation (1:1) was done electronically, in blocks stratified by sex and disease severity. Subjects and investigators were blinded to allocation.

Primary and secondary outcome measures: Primary endpoints were changes from baseline in RAND-36 PF and RP at 13 weeks. Efficacy was analysed on an intention-to-treat basis. Harms were evaluated according to the actual treatment given.

Results: Between 15 September 2021 and 20 June 2023, 80 subjects (65 women, 15 men) were enrolled and randomised (40 in each group). The trial is completed. The primary endpoint analysis included 79 subjects (40 in HBOT and 39 in control). At 13 weeks, both groups showed improvement, with no significant difference between HBOT and placebo in PF (least square mean difference between groups (LSD), 0.63 (95% CI -7.04 to 8.29), p=0.87) and RP (LSD, 2.35 (95% CI -5.95 to 10.66), p=0.57).

Harms: 43 adverse events (AEs), most commonly cough and chest pain/discomfort, occurred in 19 subjects (49%) of the HBOT group and 38 AEs in 18 subjects (44%) of the placebo group, one serious AE in HBOT and one death in the placebo group.

Conclusions: 10 HBOT sessions did not show more short-term benefits than placebo for long covid patients. Both groups improved, with a notable sex difference. HBOT has a favourable harm profile.

Trial registration number: ClinicalTrials.gov (NCT04842448), EudraCT (2021-000764-30). The trial was funded by Vetenskapsrådet (2022-00834), Region Stockholm (2020-0731, 2022-0674), Hjärt-Lungfonden and OuraHealth Oy.

Keywords: Clinical trials; Post-Acute COVID-19 Syndrome; Post-Infectious Disorders; Public health; Randomized Controlled Trial.

PubMed Disclaimer

Conflict of interest statement

Competing interests: AK and PL disclose funding from Swedish Research Council, Swedish Heart-Lung foundation, Region Stockholm and Oura Health Oy for the current trial. PL disclose partial support from the Ted and Michelle Endowed Chair in hyperbaric medicine research, University of California San Diego. MS discloses funding from Swedish Research Council and Dysautonomia International during the trial and previously from HLF. MS also disclose consulting fee from Swedish agency for health technology assessment of social services, speaker honoraria from Orion Pharma, Werfen and has filed a patent for pharmacological treatment in post-COVID POTS. JK disclose consulting fee for statistical work in this trial. AH, EB, SEG, SA-E, AS, KF, JK, JB, MNB, MR and KAR-W declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1. Trial overview/panel A shows the trial design. The trial involved five visits over 52 weeks. Panel B shows the CONSORT flow diagram. 129 patients were assessed for eligibility, 90 patients signed an informed consent form (ICF), 83 patients were screened, 80 subjects were randomised, 40 in each group. One subject in the HBOT group received sham treatment. CONSORT, Consolidated Standards of Reporting Trials; HBOT, hyperbaric oxygen treatments; PF, physical functioning.
Figure 2
Figure 2. Primary endpoints PF and RP (full analysis set). RAND-36 scores for PF and RP for the respective groups at 13 weeks. Data are presented as mean and whiskers represent SEM. HBOT, hyperbaric oxygen treatment; PF, physical functioning; RP, role limitations due to physical health.
See this image and copyright information in PMC

References

    1. Davis HE, McCorkell L, Vogel JM, et al. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21:133–46. doi: 10.1038/s41579-022-00846-2. - DOI - PMC - PubMed
    1. Soriano JB, Murthy S, Marshall JC, et al. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22:e102–7. doi: 10.1016/S1473-3099(21)00703-9. - DOI - PMC - PubMed
    1. Hedberg P, Granath F, Bruchfeld J, et al. Post COVID-19 condition diagnosis: A population-based cohort study of occurrence, associated factors, and healthcare use by severity of acute infection. J Intern Med. 2023;293:246–58. doi: 10.1111/joim.13584. - DOI - PMC - PubMed
    1. Greenhalgh T, Sivan M, Perlowski A, et al. Long COVID: a clinical update. Lancet. 2024;404:707–24. doi: 10.1016/S0140-6736(24)01136-X. - DOI - PubMed
    1. Ladyzhets B. Underwhelming”: NIH trials fail to test meaningful long Covid treatments—after 2·5 years and $1 billion. Stat News. 2023 https://www.statnews.com/2023/08/09/long-covid-nih-trials/ Available.

Publication types

Associated data