Zilberman-Itskovich 2022 RCT showed HBOT significantly improved cognitive function, fatigue, and sleep in long COVID patients at 2.0 ATA × 40 sessions.
Quality: Moderate Weak recommendation
Zilberman-Itskovich 2022 sham-controlled RCT at 2.0 ATA shows cognitive + imaging benefit. Single-centre; multicentre replication pending.
The 2022 Zilberman-Itskovich et al. randomised controlled trial (Efrati group) demonstrated statistically significant improvements in cognitive function, fatigue, sleep, and psychiatric symptoms in long COVID patients treated with 40 HBOT sessions at 2.0 ATA versus sham. This is the strongest HBOT evidence for post-viral conditions to date.
HBOT addresses several hypothesised long COVID mechanisms. Elevated plasma oxygen reverses the microvascular hypoxia hypothesised to drive brain fog and exercise intolerance. Reduced microglial activation and shifted macrophage polarisation address neuroinflammation. Improved mitochondrial function supports energy production in post-infectious fatigue. The Zilberman-Itskovich trial documented objective perfusion MRI changes in brain regions corresponding to clinical improvement — supporting a vascular/perfusion mechanism as central.
| Typical protocol | 40 sessions at 2.0 ATA, 90 minutes each, 5 days/week |
|---|---|
| Evidence level | RCT (Phase 2) — Promising evidence |
| FDA / regulatory status | Not FDA-approved |
The Zilberman-Itskovich protocol: 40 sessions over 60 days, each 90 minutes at 2.0 ATA with scheduled 5-minute air breaks every 20 minutes. Pre- and post-course assessment includes cognitive batteries (attention, executive function, processing speed), physical measures (6-minute walk), quality of life questionnaires, and perfusion MRI.