Photobiomodulation for cognitive dysfunction Brain Fog in post-COVID-19 condition: a randomized double-blind sham-controlled pilot trial, 2026, Lim+

[SNT Gatchaman]

Photobiomodulation for cognitive dysfunction Brain Fog in post-COVID-19 condition: a randomized double-blind sham-controlled pilot trial

Spoiler: Authors

Lew Lim; Nazanin Hosseinkhah; Mark Van Buskirk; Kevin Oei; Andrea Berk; Abhiram Pushparaj; Janine Liburd; Zara Abbaspour; Jonathan Rubine; David Jackson; Reza Zomorrodi

BACKGROUND
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.

METHODS
This randomized, double-blind, sham-controlled pilot trial in the USA (ClinicalTrials.gov NCT05857124) 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 brains 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.

FINDINGS
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).

INTERPRETATION
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.

FUNDING
Vielight Inc.

Web | DOI | PDF | Lancet: eClinicalMedicine | Open Access

 

[SNT Gatchaman]

Declaration of interests
All authors received compensation from Vielight either as employees or consultants/advisors. We declare no other competing interests.

 

[BrightCandle]

I was interested to know how much 0.028 actually is in terms of improvement so went hunting for the scale. Is it 2.8% or is this a big improvement. I am not really any clearer but I did find on the sites main website the mean score might be 4 with 3-5 being typical range (https://creyos.com/). This would suggest this is a miniscule improvement but reaching significance but definitely not significant improvement.

 

[forestglip]

I was interested to know how much 0.028 actually is in terms of improvement so went hunting for the scale.

I think you might be looking at the p-value, which isn't a measure of effect size. The difference between groups looks to be 0.059.

Prespecified, age-stratified exploratory analyses indicated that the pattern of effects favored the <45-year cohort on the composite cognitive score at Day 56; these subgroup findings are exploratory and not multiplicity-adjusted. In this group, active itPBM improved significantly more than sham (LS mean + 0.082 vs + 0.023; difference 0.059, 95% CI 0.007–0.111; p = 0.028), corresponding to a moderate effect size (Cohen's d ≈ 0.44).

 

[Utsikt]

I can’t find any info about blinding. If the thing shines light up your nose, would you not be aware of it?

Their Pro helmet costs $5,000.

 

[Kitty]

Their Pro helmet costs $5,000.

The whole thing looks like a revival of the tradition of using research papers as a persuasive form of marketing copy. It started in the early 2000s, when it became clear via social media that people with difficult to treat illnesses were reading and sharing academic papers.

 

[ScoutB]

I can’t find any info about blinding. If the thing shines light up your nose, would you not be aware of it?

I am very skeptical of this research but, for what it's worth, it sounds like the sham devices would turn themselves off as soon as they could tell they were on your head. Hard to know if that'd be effective or not.

Active and sham devices were identical visually with similar auditory cues and identified by randomization codes. Study personnel and participants were blinded to device allocation. [...] Sham devices mimicked operation without light delivery, using internal sensors to disable output on scalp contact.

If you're saying that they didn't seem to check if the blinding was effective, I agree, I don't see anything on that either. (Though I only skimmed.)


From the sounds of it, they shine lights both in the nose and on the scalp. The scalp seems particularly unlikely to work. There's intriguing research on this in mice, but human skulls are obviously much thicker, and it seems we have no idea if the light even penetrates (and when I've looked it up in the past, other researchers seemed to think it's unlikely).