This article is part of the HBOT Radar series, where we summarize the latest published hyperbaric oxygen therapy research.
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Disclaimer: This article is intended for educational and informational purposes only. It summarizes published medical research conducted in clinical settings and does not evaluate Brain Spa Hyperbaric products. The hyperbaric chambers offered on this website are non-medical wellness devices and are not intended to diagnose, treat, cure, or prevent any disease. Do not make medical decisions based on this article — consult a qualified healthcare professional.
📌 A Swedish Trial Said HBOT Didn't Help Long COVID. But Look at What They Actually Compared.
🔍 What this study tested
The HOT-LoCO trial out of Karolinska University Hospital in Stockholm was designed to test whether 10 HBOT sessions could improve Long COVID symptoms. It was published in BMJ Open — a solid peer-reviewed journal — and it's been widely cited as evidence that "HBOT doesn't work for Long COVID."
The headline result: no significant difference between the HBOT group and the control group.
But before accepting that conclusion, we need to look carefully at two things: what the "sham" actually was, and whether 10 sessions delivered twice a week is a fair test of a therapy whose proposed mechanism depends on cumulative, frequent exposure.
🌬️ The protocol — and why it matters
- Design: Randomized, placebo-controlled, double-blind, phase II trial
- Location: Karolinska University Hospital, Stockholm
- Patients: Previously healthy adults aged 18-60, diagnosed with Long COVID
- HBOT group: 10 sessions over 6 weeks, 100% oxygen at 2.4 ATA, 90 minutes
- "Sham" group: Medical air (21% oxygen) at 1.34–1.2 ATA, 90 minutes
10 sessions over 6 weeks = roughly 1.7 sessions per week.
For comparison, the Israeli trial that showed significant Long COVID improvements used 40 sessions, 5 times per week, over 8 weeks.
That's not just "more sessions" — it's a fundamentally different dosing strategy. HBOT's proposed mechanisms — neuroplasticity, angiogenesis, immune modulation — are thought to work through repeated hyperoxic-hypoxic cycles that build on each other. Running once or twice a week, with days of normoxia between sessions, may not generate enough cumulative signal to trigger these adaptive processes. It's the difference between watering a plant once a week and watering it daily — the total amount of water might eventually add up, but the biological response is very different.
⚠️ The sham problem: this wasn't a placebo
Here is where the study's design raises serious questions.
The "sham" group breathed normal air (21% oxygen) at 1.34–1.2 ATA for 90 minutes per session.
This is not biologically inert. And this is not a new controversy — it's the same fundamental design flaw that Dr. Paul Harch and other researchers have been pointing out for over a decade.
What happens at 1.3 ATA with normal air? The pressure alone increases the partial pressure of inspired oxygen — even without supplemental oxygen. At 1.3 ATA, you're breathing air at approximately 0.27 ATA pO₂, compared to 0.21 ATA at sea level. That's a roughly 30% increase in inspired oxygen partial pressure. More importantly, the pressure itself has measurable biological effects:
- Stem cell mobilization: MacLaughlin et al. (2023, Frontiers in Neurology) showed that 10 sessions of room air at 1.27 ATA produced a 2-3 fold increase in circulating CD34+ stem/progenitor cells in healthy adults — a significant biological signal from "just" pressurized air
- Symptom improvement in DoD trials: Across four US Department of Defense trials for mild TBI (Wolf 2012, Cifu 2014, Miller 2015, Weaver 2018), the 1.2-1.3 ATA air "sham" arms consistently showed significant within-group improvement — in some cases matching or exceeding the active HBOT arms
- Dissolved oxygen increase: Even at 1.3 ATA with room air, plasma dissolved oxygen rises by approximately 30-50% — a small but real physiological change over 90 minutes
The Miller 2015 HOPPS trial is particularly instructive: the "sham" group (1.2 ATA air, 40 sessions) showed statistically significant improvement on the primary outcome (RPQ score, p = 0.02) — while the no-chamber control group showed zero improvement. This strongly suggests that pressurized air at 1.2 ATA is doing something beyond placebo.
So what does this mean for HOT-LoCO? Both groups — the "HBOT" group and the "sham" group — were receiving pressurized treatment. The study wasn't comparing HBOT to nothing. It was comparing high-dose HBOT (2.4 ATA, 100% O₂) to low-dose pressurized air (1.3 ATA, 21% O₂). When both groups improve but there's "no significant difference," the most straightforward interpretation isn't that HBOT doesn't work — it's that both interventions may have been active.
📊 The result in context
Both groups in HOT-LoCO improved over time. No significant difference between groups.
There are three possible explanations:
1. HBOT doesn't work for Long COVID at any dose. Possible, but contradicted by the positive Israeli 40-session sham-controlled trial (Zilberman-Itskovich et al., 2022, Scientific Reports), which used a true 1.0 ATA sham and showed significant cognitive and quality-of-life improvements.
2. Ten sessions, twice weekly, isn't enough. Highly plausible. The Israeli protocol was four times as many sessions at three times the weekly frequency. HBOT is understood to be cumulative — 10 low-frequency sessions may simply be below the therapeutic threshold.
3. The "sham" was also therapeutic. Supported by a decade of DoD trial data and the MacLaughlin 2023 stem cell study. If the control group is also receiving a bioactive intervention, you'd expect both groups to improve similarly — which is exactly what happened.
The most likely reality is a combination of explanations 2 and 3. An underdosed HBOT protocol was compared against an active comparator, at a frequency too low to trigger cumulative effects. In this design, a "negative" result is almost guaranteed.
🧠 What this actually tells us
This study does not show that HBOT doesn't work for Long COVID. What it shows is that 10 sessions of HBOT, delivered roughly twice a week, didn't outperform 10 sessions of pressurized air delivered at the same frequency.
The more important questions — Does 40+ sessions at 5x/week help? Does the sham-arm improvement represent a real low-dose effect? What's the minimum effective dose? — remain unanswered by this trial.
Credit where it's due: the Karolinska team designed and executed a rigorous trial. The randomization, blinding, and statistical methods are solid. The problem isn't the execution — it's the assumptions built into the design. Treating 1.3 ATA pressurized air as "placebo" when a growing body of evidence suggests it's biologically active creates a study that, by design, makes it very difficult to find a difference even if HBOT does work.
And the study does confirm one thing: both protocols were safe and well-tolerated, with no serious adverse events in either group.
📌 Takeaway for the community
- A Swedish RCT (HOT-LoCO) found no difference between 10 HBOT sessions and "sham" treatment for Long COVID — but the study design has two significant issues that complicate this conclusion
- The "sham" was pressurized air at 1.34-1.2 ATA — not biologically inert. A decade of DoD trial data and the MacLaughlin 2023 study show measurable biological effects at this pressure, including stem cell mobilization and symptom improvement in brain injury patients
- 10 sessions delivered roughly twice a week is a fundamentally different dose than the positive Israeli trial's 40 sessions at 5x/week — HBOT's cumulative mechanisms may require higher frequency to take effect
- Both groups improved, which is consistent with both interventions being active rather than HBOT being ineffective
- This study does not close the door on HBOT for Long COVID — it highlights that dose, frequency, and sham design are critical questions the field still needs to answer
- This study was conducted at Karolinska University Hospital under medical supervision — results cannot be directly applied to other settings or devices
Source: https://pubmed.ncbi.nlm.nih.gov/40228859/
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. Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid (HOT-LoCO): a randomised, placebo-controlled, double-blind, phase II trial. BMJ Open. 2025 Apr 14;15(4):e094386. doi: 10.1136/bmjopen-2024-094386.
Educational disclaimer
This content summarizes findings from published medical research for educational purposes only.
The hyperbaric chambers sold on this website are non-medical wellness devices and are not intended to diagnose, treat, cure, or prevent any disease.
The studies discussed here were conducted in clinical medical settings using medical-grade interventions. The inclusion of research summaries does not imply that similar outcomes can be achieved using non-medical wellness devices.
