Kjellberg A, Hassler A, Boström E, El Gharbi S, Al-Ezerjawi S, Schening A, Fischer K, Kowalski JH, Rodriguez-Wallberg KA, Bruchfeld J, Ståhlberg M, Nygren-Bonnier M, Runold M, Lindholm P, et al.
BMJ open. Date of publication 2025 Apr 14;volume 15(4):e094386.
1. BMJ Open. 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.
Kjellberg A(1)(2), Hassler A(3), Boström E(3), El Gharbi S(3), Al-Ezerjawi S(3),
Schening A(2), Fischer K(4)(5), Kowalski JH(6), Rodriguez-Wallberg KA(7)(8),
Bruchfeld J(4)(9), Ståhlberg M(4)(5), Nygren-Bonnier M(10)(11), Runold
M(12)(13), Lindholm P(14)(15).
Author information:
(1)Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm,
Sweden anders.kjellberg@ki.se.
(2)Perioperative Medicine and Intensive Care, Medical Unit Intensive Care and
Thoracic Surgery, Karolinska University Hospital, Stockholm, Sweden.
(3)Medical Unit Emergency Medicine, Karolinska University Hospital, Stockholm,
Sweden.
(4)Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
(5)Medical Unit Cardiology, Heart and Vascular Center, Karolinska University
Hospital, Stockholm, Sweden.
(6)JK Biostatistics AB, Stockholm, Sweden.
(7)Department of Oncology and Pathology, Karolinska Institutet, Stockholm,
Sweden.
(8)Department of Reproductive Medicine, Karolinska University Hospital,
Stockholm, Sweden.
(9)Department of Infectious Diseases, Karolinska University Hospital, Stockholm,
Sweden.
(10)Department of Neurobiology, Care Sciences and Society, Karolinska
Institutet, Stockholm, Sweden.
(11)Women's Health and Allied Health Professionals Theme, Medical Allied Health
Professionals, Karolinska University Hospital, Stockholm, Sweden.
(12)Department of Medicine Solna, Respiratory Medicine Unit, Karolinska
Institutet, Stockholm, Sweden.
(13)Department of Respiratory Medicine and Allergy, Karolinska University
Hospital, Stockholm, Sweden.
(14)Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm,
Sweden.
(15)Department of Emergency Medicine, Division of Hyperbaric Medicine,
University of California San Diego, La Jolla, California, USA.
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.
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published
by BMJ Group.
DOI: 10.1136/bmjopen-2024-094386
PMCID: PMC11997836
PMID: 40228859 [Indexed for MEDLINE]
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.
