Zilberman-Itskovich et al. (2022, Scientific Reports) is the trial that put HBOT for Long COVID on the published-evidence map. It is a randomized, double-blind, sham-controlled clinical trial — the strongest single design in clinical research — and to date the largest published HBOT trial focused on the post-COVID condition.
What the trial measured. Seventy-three patients with documented post-COVID condition (cognitive symptoms persisting at least three months after acute infection) were randomized to either active HBOT or a sham control. The primary endpoints spanned five distinct domains: global cognitive function, energy/fatigue, sleep quality, psychiatric symptoms, and pain interference. Brain MRI perfusion and microstructural imaging served as objective secondary endpoints — important because they are not vulnerable to self-report bias.
Who was studied. The cohort was 37 active-HBOT patients and 36 sham-control patients, with documented post-COVID cognitive symptoms persisting beyond the acute infection window. Inclusion required objective cognitive impairment on standardized testing at baseline, ruling out studies of patients with merely subjective complaints.
Protocol parameters. Active-arm participants received 40 daily HBOT sessions over approximately eight weeks. Sham-arm participants received a sham protocol of equal duration so that neither patients nor outcome evaluators knew assignment — the gold-standard blinding for HBOT trials, which is notoriously hard to blind.
Results. The active-HBOT group showed statistically significant improvements over sham across cognition (attention, executive function, memory, information processing speed), energy and fatigue, sleep, psychiatric symptoms, and pain interference. The brain MRI findings provided the objective backbone: perfusion and microstructural changes were documented in multiple regions including the supramarginal gyrus, supplementary motor area, insula, precentral gyrus, middle frontal gyrus, and corona radiata. The authors concluded that ‘HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition.’
Limitations. The trial size (n=73) is modest — typical for HBOT but small by general drug-trial standards. The sham was a passive-air protocol; while standard for HBOT, it does not perfectly blind to the chamber experience. The follow-up window was short — but Hadanny et al. 2024 later followed 31 of these patients to approximately one-year post-protocol and found that cognitive, sleep, and quality-of-life gains were largely sustained, addressing the durability question.
What it means in practice. The Zilberman-Itskovich 2022 protocol — 40 sessions at 2.0 ATA, 100% oxygen with intermittent air breaks, 90-minute sessions, five days per week — is the directly-cited reference for HBOT in Long COVID. Soft-shell home chambers cap at 1.5 ATA and cannot replicate the 2.0 ATA protocol; for Long COVID specifically, the published evidence is for the clinical-chamber protocol.
How it relates to other indexed trials. The mechanism story (addressing microthrombosis, mitochondrial dysfunction, and neuroinflammation simultaneously) is the same biology HBOT engages in Long COVID, post-stroke recovery, and TBI — a multi-system regenerative cascade rather than a single-target effect. The Hadanny 2024 long-term follow-up confirmed durability. Together with Doenyas-Barak 2022 (PTSD) and Hachmo 2020 (longevity), this paper anchors several Saturate condition pages on what is currently the strongest HBOT evidence in published RCTs.
Source: PubMed PMID 35821512.