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

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. Clinical trial registration http://www.chictr.org.cn/ , identifier ChiCTR2300071190.