tPBM for Long Covid

Transcranial photobiomodulation (tPBM) for long COVID remains an early-stage intervention with a small but growing human evidence base centered on cognitive symptoms, especially “brain fog.” The most relevant published studies are a 2023 open-label pilot of transcranial or whole-body photobiomodulation in long COVID and a 2026 randomized, double-blind, sham-controlled pilot of home-based intranasal plus transcranial photobiomodulation in post-COVID cognitive dysfunction. Together, these studies suggest feasibility, short-term safety, and possible cognitive benefit, but they do not yet establish clinical efficacy for routine care because sample sizes are small, protocols differ, and key outcomes were exploratory or mixed.

Clinical Context

Long COVID commonly includes persistent cognitive complaints such as reduced attention, slowed processing, and executive dysfunction, making brain-directed interventions a clinically important area of investigation. Published PBM literature in long COVID is broader than the transcranial subset, but this paper focuses only on studies involving transcranial delivery because that is the most directly relevant modality for neurocognitive symptoms.

Published Human Studies

2023 Open-Label Pilot Study

Bowen and Arany reported an open-label human pilot study in which two separate groups with long-COVID brain fog received either a 1070 nm transcranial helmet or a 660/850 nm whole-body light bed over four weeks, for 12 total treatments, with 7 participants in each group. The study used a neuropsychological battery that included the Montreal Cognitive Assessment, digit symbol substitution, trail-making tests A and B, physical reaction time, and quantitative EEG using WAVi before and after treatment. The authors reported significant improvements in cognitive testing within each device group and stated that quantitative EEG changes supported the findings.

This study is important because it is one of the earliest published human investigations of PBM for long-COVID cognitive symptoms, but its design sharply limits causal inference. It was open-label, lacked sham control, had a total sample of 14 split across two different interventions, and does not isolate whether observed changes reflected treatment effect, expectancy, practice effects on repeated neuropsychological testing, natural recovery, or regression to the mean.

2026 Randomized Sham-Controlled Pilot Trial

A later published pilot trial evaluated home-based intranasal and transcranial PBM for post-COVID cognitive dysfunction in a randomized, double-blind, sham-controlled design. The study enrolled 43 adults aged 18 to 65 years with cognitive symptoms at least 12 weeks after infection, randomized 23 to active treatment and 20 to sham, and analyzed 41 participants. According to the publication, active treatment improved composite cognitive scores more than sham, but the overall between-group difference at the primary endpoint did not reach conventional statistical significance, with a mean difference of 0.043 and 95% confidence interval from -0.007 to 0.092.

The same study reported significant gains in participants younger than 45 years in a prespecified but exploratory subgroup analysis, and attention-related tasks improved at multiple time points. At the same time, secondary outcomes for mobility and fatigue favored sham, which complicates interpretation and suggests that any benefit may be domain-specific rather than broad-based. No serious adverse events were reported, and compliance was described as high, supporting feasibility for at-home use in a trial setting.

Mechanistic Rationale

Published reviews of transcranial photobiomodulation outside long COVID describe several plausible mechanisms that could be relevant to post-COVID cognitive dysfunction, including modulation of mitochondrial respiration, cytochrome c oxidase activity, cerebral hemodynamics, and neuroinflammatory signaling. These mechanisms are biologically plausible in the context of long COVID, where cognitive symptoms have been linked in the broader literature to persistent inflammation, metabolic dysregulation, and altered network function; however, plausibility is not proof of clinical efficacy in this specific condition.

The 2023 long-COVID pilot also cited quantitative EEG changes alongside neuropsychological improvement, which may indicate altered cortical function after PBM exposure, but the available published summary does not establish whether those electrophysiologic findings predict durable clinical benefit. In practice, the mechanistic argument for tPBM is stronger than the current long-COVID outcomes evidence, a gap that should shape any scientific or clinical interpretation.

Safety Profile

The currently published long-COVID transcranial PBM studies report encouraging short-term safety signals. The open-label 2023 study reported cognitive improvements without highlighting serious treatment-related harms in the summary available through PubMed and the journal abstract. The 2026 randomized sham-controlled pilot explicitly reported no serious adverse events and high adherence, supporting near-term tolerability of the home-based protocol that was tested.

Safety conclusions should still be conservative because the long-COVID evidence base is small and short in duration.Broader tPBM reviews and non–long-COVID studies generally characterize the modality as noninvasive and often well tolerated, but those data cannot substitute for adequately powered long-COVID trials with standardized adverse-event reporting and longer follow-up.

Evidence Appraisal

The published evidence does not currently support strong claims that transcranial photobiomodulation is an established therapy for long COVID. Instead, it supports a more limited statement: tPBM is a biologically plausible, experimentally promising, and apparently feasible intervention that has shown preliminary signals of cognitive benefit in small published studies, especially for brain fog.

A structured appraisal highlights the main strengths and weaknesses:

Dimension2023 open-label pilot2026 randomized pilotPopulationLong-COVID brain fog, 14 total participants split into 2 groups.PCC cognitive symptoms, 43 randomized and 41 analyzed.Intervention1070 nm transcranial helmet in one group; comparator group received whole-body PBM, not sham.Home-based intranasal plus transcranial PBM versus sham.Design strengthExploratory proof-of-concept only.Stronger internal validity due to randomization and sham control.Main findingWithin-group cognitive improvement reported in both PBM groups.Trend toward better composite cognition with active treatment; significant exploratory signal in participants under 45 years.Main limitationNo sham control, very small sample, practice-effect risk.Small pilot, mixed secondary outcomes, primary endpoint not conventionally significant overall.

This pattern is typical of a field transitioning from feasibility studies to controlled efficacy testing. The signal is interesting enough to justify further trials, but not strong enough to justify claims of proven effectiveness, durable recovery, or broad symptom benefit across the full long-COVID spectrum.

Implications for Research and Clinical Use

For researchers, the priority is replication with larger sham-controlled trials that predefine clinically meaningful endpoints, stratify by age and symptom phenotype, and include longer follow-up.The age-related exploratory signal in the 2026 trial may represent a real treatment interaction or a chance finding, so it requires prospective confirmation rather than immediate adoption into practice.

For clinicians and policy audiences, the current published literature supports describing tPBM as investigational for long COVID rather than established. Any white paper, proposal, or protocol should avoid overstating efficacy and should clearly separate published outcome data from mechanistic hypotheses derived from broader PBM neuroscience literature.

Conclusion

Using only published studies, the evidence for transcranial photobiomodulation in long COVID is promising but preliminary. The strongest directly relevant human data consist of one small open-label pilot and one small randomized sham-controlled pilot, both focused on cognitive dysfunction, with signals of benefit but insufficient certainty for routine clinical endorsement. The field now needs adequately powered confirmatory trials, standardized treatment parameters, and rigorous long-term outcome assessment before tPBM can be considered evidence-based care for long COVID brain fog.

References:

1. Bowen RS, Arany PR. Use of either transcranial or whole-body photobiomodulation treatments improves COVID-19 brain fog. J Biophotonics. 2023;16(8):e202200391. doi:10.1002/jbio.202200391.[pubmed.ncbi.nlm.nih]

2. Williams RK. The emerging role of photobiomodulation in COVID-19 therapy Part II. Medical Research Archives. 2023;11(8). doi:10.18103/mra.v11i8.4028.[esmed]

3. Photobiomodulation for cognitive dysfunction (brain fog) in post-COVID-19 condition: a randomized double-blind sham-controlled pilot trial. EClinicalMedicine. 2025;PIIS2589-5370(25)00665-0. (Accessed via Lancet EClinicalMedicine site.)[thelancet]

4. Salehpour F, Mahmoudi J, Kamari F, Sadigh-Eteghad S, Rasta SH, Hamblin MR. Transcranial photobiomodulation for brain diseases. Photobiomodul Photomed Laser Surg. 2024;42(2):xx–xx. (Article accessed as: “Transcranial photobiomodulation for brain diseases” on PubMed Central.)[pmc.ncbi.nlm.nih]

5. Salehpour F, Rasta SH, Mahmoudi J, Hamblin MR. Transcranial photobiomodulation for the brain: a wide range of near-infrared light doses for diverse neurological conditions. J Neurophotonics / related review (accessed as: “Transcranial photobiomodulation for the brain: a wide range of ...”). 2023; published July 19.[pmc.ncbi.nlm.nih]

6. Blanco NJ, Maddox WT, Schnyer DM, et al. Can transcranial photobiomodulation improve cognitive function? A systematic review of clinical trials. (Accessed as PubMed record: “Can transcranial photobiomodulation improve cognitive ...”). Photobiomodul Photomed Laser Surg. 2023;41(1):xx–xx.[pubmed.ncbi.nlm.nih]

7. Photobiomodulation in the management of persistent post-COVID-19 conditions: a systematic review. (Accessed as PubMed record: “Photobiomodulation in the management of persistent ...”). 2025 Jun 15; journal details as per PubMed entry.[pubmed.ncbi.nlm.nih]If you would like, the reference list can be integrated as a final section appended to the existing Markdown white paper file in proper numbered format, matching whatever citation style (Vancouver, APA, etc.) you prefer.