Photobiomodulation for cognitive dysfunction (Brain Fog) in post-COVID-19 condition: a randomized double-blind...

Post-COVID-19 condition (PCC) affects millions globally, with cognitive dysfunction ("brain fog") impairing daily functioning in up to 88% of patients. No effective treatments exist for PCC-related cognitive impairment. Photobiomodulation (PBM), a non-invasive therapy delivering near-infrared light, enhances mitochondrial function and reduces neuroinflammation, showing promise in neurological disorders. This study aimed to evaluate the efficacy and safety of home-based intranasal and transcranial PBM (itPBM) for PCC cognitive dysfunction.

This randomized, double-blind, sham-controlled pilot trial in the USA (ClinicalTrials.govNCT05857124) enrolled 43 adults (18-65 years) with PCC cognitive symptoms ≥12 weeks post-infection. Participants were randomized 1:1, stratified by age (<45 vs ≥ 45 years), using computer-generated assignment to 8 weeks of daily 20-min itPBM, 6 days per week, with the Vielight Neuro RX Gamma device or sham, targeting the brain's default mode network, followed by 4 weeks of observation. Participants, investigators, and assessors were masked to group assignment. The primary outcome was mean change in Creyos cognitive battery composite score at Day 56. Secondary outcomes included fatigue, quality of life, and safety. Analyses used mixed-model repeated measures in the per-protocol population.

The trial was completed, with 43 participants randomized (23 active, 20 sham) and 41 analyzed (21 active, 20 sham). They were recruited between July 5, 2023, and September 1, 2024. Active itPBM improved composite cognitive scores more than sham (mean difference 0.043, 95% CI -0.007 to 0.092, p = 0.088), with significant gains in participants <45 years (prespecified but exploratory, p = 0.028). Attention tasks improved consistently (p < 0.050 at multiple timepoints). Secondary outcomes mobility favored sham (p = 0.007), and fatigue also favored sham. No serious adverse events occurred; compliance was high (median 55 days, interquartile range 2 days).

Home-based itPBM is safe and feasible, showing potential cognitive benefits for PCC brain fog, particularly in younger adults. Larger trials are needed to confirm efficacy and optimize parameters.

Vielight Inc.