CLINICAL TRIAL article
Front. Psychiatry
Sec. Sleep Disorders
Remote ischemic conditioning improves neuropsychiatric symptoms in COVID-19 patients: A Randomized Clinical Trial
Provisionally accepted
Jinbiao Zhang1*
Yaxuan Wu1Mengfan Li1Hiaying Li2Hui LI1Tengqun Shen1Yuanyuan Liu1Guangming Wang1Hairong Sun1Zhenguang Li1- 1Weihai Municipal Hospital, Weihai, China
- 2Shandong Second Medical University, Weifang, China
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Background 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. Methods: 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. Results: 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). Conclusions: Our study suggested that RIC may be a potential adjuvant therapy for neuropsychiatric symptoms after COVID-19.
Keywords: cognitive impairment, COVID-19, Inflammation, insomnia, Remote ischemic precondition
Received: 28 Jul 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Zhang, Wu, Li, Li, LI, Shen, Liu, Wang, Sun and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jinbiao Zhang
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