# Remote ischemic conditioning improves neuropsychiatric symptoms in COVID-19 patients: a randomized clinical trial

**Authors:** Yaxuan Wu, Mengfan Li, Haiying Li, Hui Li, Tengqun Shen, Yuanyuan Liu, Guangming Wang, Hairong Sun, Zhenguang Li, Jinbiao Zhang

PMC · DOI: 10.3389/fpsyt.2025.1674886 · Frontiers in Psychiatry · 2026-02-20

## TL;DR

This study shows that remote ischemic conditioning can improve cognitive and sleep issues in patients recovering from COVID-19.

## Contribution

The study is the first to demonstrate RIC's effectiveness in improving neuropsychiatric symptoms in post-COVID-19 patients.

## Key findings

- RIC significantly improved cognitive scores and reduced sleep and anxiety symptoms in patients at 3 months.
- The positive effects of RIC persisted even after treatment ended.
- RIC showed statistically significant improvements across multiple neuropsychiatric metrics.

## Abstract

Coronavirus disease 2019 (COVID-19) may induce cognitive impairment, insomnia, anxiety, and depression through secondary inflammatory reaction. Remote ischemic conditioning (RIC), a promisingly noninvasive intervention, can modulate the inflammatory reaction in target organs and offer organ protection.

This randomized, placebo-controlled, double-blinded trial recruited 65 patients with COVID-19-related insomnia to investigate whether RIC can improve neuropsychiatric symptoms in COVID-19 patients. Participants were evaluated for neuropsychiatric symptoms including cognition (Beijing version of the Montreal Cognitive Assessment (MoCA)), sleep (Pittsburgh Sleep Quality Index (PSQI), 14-item Fatigue Scale (FS-14) and Epworth Sleepiness Scale (ESS)), anxiety (Hamilton Anxiety Scale (HAMA)) and depression (Hamilton Depression Scale (HAMD-17)). Serum neuronal-derived exosomes (NDEs) complement proteins and mitochondria proteins were extracted and quantified.

MoCA score was significantly ameliorated in the RIC group and the PSQI, FS-14, ESS, HAMA and HAMD-17 scores were remarkably decreased in the RIC group at 3 months (P < 0.001 for MoCA, PSQI, FS-14, and ESS; P = 0.003 for HAMA; P = 0.005 for HAMD-17). The interaction effect of time-by group was also different (P < 0.001 for MoCA, PSQI, FS-14, and ESS; P = 0.003 for HAMA). Furthermore, the PSQI, FS-14, ESS, HAMA, and HAMD-17 scores were statistically decreased in the RIC group at three months after the end of RIC treatment (P < 0.001 for MoCA, PSQI, FS-14, and ESS; P = 0.03 for HAMA; P = 0.027 for HAMD-17).

Our study suggested that RIC may be a potential adjuvant therapy for neuropsychiatric symptoms after COVID-19.

## Linked entities

- **Diseases:** Coronavirus disease 2019 (MONDO:0100096), insomnia (MONDO:0013600), anxiety (MONDO:0005618), depression (MONDO:0002050)

## Full-text entities

- **Genes:** APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MCU (mitochondrial calcium uniporter) [NCBI Gene 90550] {aka C10orf42, CCDC109A, HsMCU}, TAS2R62P (taste 2 receptor member 62, pseudogene) [NCBI Gene 338399] {aka PS1, T2R62, TAS2R62}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, EDN1 (endothelin 1) [NCBI Gene 1906] {aka ARCND3, ET1, HDLCQ7, PPET1, QME}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, DOCK3 (dedicator of cytokinesis 3) [NCBI Gene 1795] {aka MOCA, NEDIDHA, PBP}, SLC8A1 (solute carrier family 8 member A1) [NCBI Gene 6546] {aka NCX1}, NDE1 (nudE neurodevelopment protein 1) [NCBI Gene 54820] {aka HOM-TES-87, LIS4, MHAC, NDE, NUDE, NUDE1}, LGI1 (leucine rich glioma inactivated 1) [NCBI Gene 9211] {aka ADLTE, ADPAEF, ADPEAF, DEE121, EPITEMPIN, EPT}, THBS1 (thrombospondin 1) [NCBI Gene 7057] {aka THBS, THBS-1, TSP, TSP-1, TSP1}, SLC24A3 (solute carrier family 24 member 3) [NCBI Gene 57419] {aka NCKX3}, CFB (complement factor B) [NCBI Gene 629] {aka AHUS4, ARMD14, BF, BFD, CFAB, CFBD}, ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}
- **Diseases:** Parkinson's disease (MESH:D010300), mitochondrial (MESH:D028361), fractures (MESH:D050723), vascular impairments (MESH:D020141), Sleep Disorders (MESH:D012893), Hyperlipidemia (MESH:D006949), injuries (MESH:D014947), neurodegenerative disease (MESH:D019636), inflammation (MESH:D007249), dementia with Lewy bodies (MESH:D020961), Anxiety (MESH:D001007), neuroinflammation (MESH:D000090862), traumatic brain injury (MESH:D000070642), ischemic (MESH:D002545), Diabetes (MESH:D003920), malignant tumor (MESH:D009369), neuropsychiatric symptoms (MESH:D001523), Alzheimer's disease (MESH:D000544), Insomnia (MESH:D007319), stroke (MESH:D020521), Fatigue (MESH:D005221), multiple system atrophy (MESH:D019578), autoimmune reaction (MESH:D001327), bleeding (MESH:D006470), systemic diseases (MESH:D034721), fever (MESH:D005334), ischemia (MESH:D007511), small vessel disease (MESH:D059345), COVID (MESH:D018352), heart or blood system diseases (MESH:D006402), vascular dementia (MESH:D015140), brain injury (MESH:D001930), Hypertension (MESH:D006973), long-term COVID (MESH:D000088562), EDS (MESH:D006970), NDEs (MESH:C536408), vascular injuries (MESH:D057772), vascular disorders (MESH:D002561), immune system disease (MESH:D007154), COVID-19 (MESH:D000086382), ischemic stroke (MESH:D002544), TS (MESH:D005879), infection (MESH:D007239), Encephalitis (MESH:D004660), dementia (MESH:D003704), Depression (MESH:D003866), obstructive sleep apnea (MESH:D020181), thyroid disease (MESH:D013959), brain tumors (MESH:D001932), long-term COVID-19 (MESH:D000094024), neuronal apoptosis (MESH:D065703), cognitive impairment (MESH:D003072), hydrocephalus (MESH:D006849)
- **Chemicals:** triglycerides (MESH:D014280), barbital (MESH:D001462), cholesterol (MESH:D002784), benzhexol (MESH:D014282), citicoline (MESH:D003566), benzodiazepines (MESH:D001569), melatonin (MESH:D008550), levodopa (MESH:D007980), Ca2+ (-), ROS (MESH:D017382), creatinine (MESH:D003404), piracetam (MESH:D010889)
- **Species:** Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Gammacoronavirus (genus) [taxon 694013], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12963307/full.md

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12963307/full.md

## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963307/full.md

---
Source: https://tomesphere.com/paper/PMC12963307