Kjellberg A, Hassler A, Boström E, El Gharbi S, Al-Ezerjawi S, Kowalski J, Rodriguez-Wallberg KA, Bruchfeld J, Ståhlberg M, Nygren-Bonnier M, Runold M, Lindholm P, et al.
BMC infectious diseases. Date of publication 2023 Jan 20;volume 23(1):33.
1. BMC Infect Dis. 2023 Jan 20;23(1):33. doi: 10.1186/s12879-023-08002-8.
Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report
from a randomised controlled trial.
Kjellberg A(1)(2), Hassler A(3)(4), Boström E(3)(4), El Gharbi S(3)(4),
Al-Ezerjawi S(3)(4), Kowalski J(5), Rodriguez-Wallberg KA(6)(7), Bruchfeld
J(8)(9), Ståhlberg M(10)(11), Nygren-Bonnier M(12)(13), Runold M(14)(15),
Lindholm P(3)(16).
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.
anders.kjellberg@ki.se.
(3)Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm,
Sweden.
(4)Medical Unit Emergency Medicine, Karolinska University Hospital, Stockholm,
Sweden.
(5)JK Biostatistics AB, Stockholm, Sweden.
(6)Department of Oncology and Pathology, Karolinska Institutet, Stockholm,
Sweden.
(7)Division of Gynaecology and Reproduction, Department of Reproductive
Medicine, Karolinska University Hospital, Stockholm, Sweden.
(8)Division of Infectious Diseases, Department of Medicine Solna, Karolinska
Institutet, Stockholm, Sweden.
(9)Department of Infectious Diseases, Karolinska University Hospital, Stockholm,
Sweden.
(10)Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
(11)Medical Unit Cardiology, Heart, Vascular and Neuro Theme, Karolinska
University Hospital, Stockholm, Sweden.
(12)Division of Physiotherapy, Department of Neurobiology, Care Sciences and
Society, Karolinska Institutet, Stockholm, Sweden.
(13)Women's Health and Allied Health Professionals Theme, Medical Unit
Occupational Therapy and Physiotherapy, Karolinska University Hospital,
Stockholm, Sweden.
(14)Department of Medicine Solna, Respiratory Medicine Unit, Karolinska
Institutet, Stockholm, Sweden.
(15)Department of Respiratory Medicine and Allergy, Karolinska University
Hospital, Stockholm, Sweden.
(16)Division of Hyperbaric Medicine, Department of Emergency Medicine,
University of California San Diego, La Jolla, CA, 92093, USA.
BACKGROUND: With ~ 50 million individuals suffering from post-COVID condition
(PCC), low health related quality of life (HRQoL) is a vast problem. Common
symptoms of PCC, that persists 3 months from the onset of COVID-19 are fatigue,
shortness of breath and cognitive dysfunction. No effective treatment options
have been widely adopted in clinical practice. Hyperbaric oxygen (HBO2) is a
candidate drug.
METHODS: The objective of this interim analysis is to describe our cohort and
evaluate the safety of HBO2 for post covid condition. In an ongoing randomised,
placebo-controlled, double blind, clinical trial, 20 previously healthy subjects
with PCC were assigned to HBO2 or placebo. Primary endpoints are physical
domains in RAND-36; Physical functioning (PF) and Role Physical (RP) at
13 weeks. Secondary endpoints include objective physical tests. Safety endpoints
are occurrence, frequency, and seriousness of Adverse Events (AEs). An
independent data safety monitoring board (DSMB) reviewed unblinded data. The
trial complies with Good Clinical Practice. Safety endpoints are evaluated
descriptively. Comparisons against norm data was done using t-test.
RESULTS: Twenty subjects were randomised, they had very low HRQoL compared to
norm data. Mean (SD) PF 31.75 (19.55) (95% Confidence interval; 22.60-40.90) vs
83.5 (23.9) p < 0.001 in Rand-36 PF and mean 0.00 (0.00) in RP. Very low
physical performance compared to norm data. 6MWT 442 (180) (95% CI 358-525) vs
662 (18) meters p < 0.001. 31 AEs occurred in 60% of subjects. In 20 AEs, there
were at least a possible relationship with the study drug, most commonly cough
and chest pain/discomfort.
CONCLUSIONS: An (unexpectedly) high frequency of AEs was observed but the DSMB
assessed HBO2 to have a favourable safety profile. Our data may help other
researchers in designing trials. Trial Registration ClinicalTrials.gov:
NCT04842448. Registered 13 April 2021,
https://clinicaltrials.gov/ct2/show/NCT04842448 . EudraCT: 2021-000764-30.
Registered 21 May 2021,
https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000764-30/SE.
© 2023. The Author(s).
DOI: 10.1186/s12879-023-08002-8
PMCID: PMC9854077
PMID: 36670365 [Indexed for MEDLINE]
Conflict of interest statement: AK and PL disclose funding from Swedish
Heart–Lung foundation, Stockholm Council and Oura Health Oy for the current
trial. 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, SAE, JK, JB, MNB, MR declare that
they have no known competing financial interests or personal relationships that
could have appeared to influence the work reported in this paper.
