Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (10): 3013-3024.doi: 10.4103/NRR.NRR-D-23-01651

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Persistent alterations in gray matter in COVID-19 patients experiencing sleep disturbances: a 3-month longitudinal study

Kaixuan Zhou1, 2, #, Gaoxiong Duan2, #, Ying Liu2 , Bei Peng2 , Xiaoyan Zhou2 , Lixia Qin3 , Lingyan Liang2 , Yichen Wei2 , Qingping Zhang2 , Xiaocheng Li2 , Haixia Qin2 , Yinqi Lai2 , Yian Lu3 , Yan Zhang2 , Jiazhu Huang2 , Jinli Huang2 , Yinfei Ouyang2 , Bolin Bin2 , Mingming Zhao3 , Jun Liu4, *, Jianrong Yang5, *, Demao Deng1, 2, *   

  1. 1 Guangxi Key Laboratory of Special Biomedicine; School of Medicine, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, China;  2 Department of Radiology, the People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi Zhuang Autonomous Region, China;  3 Department of Sleep Medicine, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China;  4 Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China;  5 Guangxi Clinical Research Center for Sleep Medicine, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi Zhuang Autonomous Region, China
  • Online:2025-10-15 Published:2025-02-09
  • Contact: Demao Deng, MD, demaodeng@163.com; Jianrong Yang, MBBS, gandansurgery2014@163.com; Jun Liu, MD, junliu123@csu.edu.cn.
  • Supported by:
    This study was supported by grants from Major Project of Science and Technology of Guangxi Zhuang Autonomous Region, No. Guike-AA22096018 (to JY); Guangxi Key Research and Development Program, No. AB22080053 (to DD); Major Project of Science and Technology of Guangxi Zhuang Autonomous Region, No. Guike-AA23023004 (to MZ); the National Natural Science Foundation of China, Nos. 82260021 (to MZ), 82060315 (to DD); the Natural Science Foundation of Guangxi Zhuang Autonomous Region, No. 2021GXNSFBA220007 (to GD); Clinical Research Center For Medical Imaging in Hunan Province, No. 2020SK4001 (to JL); Key Emergency Project of Pneumonia Epidemic of Novel Coronavirus Infection in Hunan Province, No. 2020SK3006 (to JL); Science and Technology Innovation Program of Hunan Province, No. 2021RC4016 (to JL); and Key Project of the Natural Science Foundation of Hunan Province, No. 2024JJ3041 (to JL).

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Abstract: Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections. Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019 (COVID-19). However, neuroimaging studies on sleep disturbances caused by COVID-19 are scarce, and existing studies have primarily focused on the long-term effects of the virus, with minimal acute phase data. As a result, little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19. To address this issue, we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection, and verified the results using 3-month follow-up data. A total of 26 COVID-19 patients with sleep disturbances (aged 51.5 ± 13.57 years, 8 women and 18 men), 27 COVID-19 patients without sleep disturbances (aged 47.33 ± 15.98 years, 9 women and 18 men), and 31 age- and gender-matched healthy controls (aged 49.19 ± 17.51 years, 9 women and 22 men) were included in this study. Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis. We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes. The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores. Additionally, we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls. The 3-month follow-up data revealed indices of altered cerebral structure (cortical thickness, cortical grey matter volume, and cortical surface area) in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances. Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection. These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.

Key words: brain structure,  cortical gray matter volume,  cortical surface area,  cortical thickness,  hippocampus,  magnetic resonance imaging,   Pittsburgh Sleep Quality Index,  severe acute respiratory syndrome coronavirus 2 infections,  sleep disturbances,  sub-cortical volume