Multimodal neuroimaging exploration of the mechanisms of sleep quality deterioration after SARS-CoV-2 Omicron infection in individuals with chronic insomnia and healthy individuals
Authors: Liu Jun , Du Yaoyao , Li Cong , Zhao Wei , Li Jinyue , Zhao Linlin , Guo Huili , Jiang Yingjia , Liu Weiyin , Zeng Song , Zhang Huiting , Guo Hu , Ouyang Xuan 
Published: November 2023

Abstract
IMPORTANCE Whether the mechanism of nervous system invasion and the brain regions targeted by the currently prevalent Omicron strain parallel those of the Delta strain is unclear. Insomnia is a prevalent and persistent issue following Delta variant infection, yet our comprehension of the connection between Omicron strains and insomnia remains limited.
OBJECTIVE To evaluate the neurological alterations induced by Omicron infection, to compare brain changes in chronic insomnia with those in exacerbated chronic insomnia in Omicron patients and to examine individuals without insomnia alongside those with new-onset insomnia.
DESIGN, SETTING, AND PARTICIPANTS In this cohort study, a total of 135 participants were recruited between January 11 and May 4, 2023, including 120 participants with different sleep statuses after infection with Omicron and 15 healthy controls. Neuropsychiatric data, clinical symptoms, and multimodal magnetic resonance imaging data were collected. The gray matter thickness and T1, T2, proton density, and perivascular space values were analyzed. Associations between changes in multimodal magnetic resonance imaging findings and neuropsychiatric data were evaluated with correlation analyses.
EXPOSURES Gray matter thickness was evaluated based on the neurological alterations induced by Omicron infection, and multimodal magnetic resonance imaging was used to explore the effects of Omicron infections on sleep patterns in various populations.
MAIN OUTCOMES AND MEASURES
Neuropsychiatric scale scores were evaluated by using IBM SPSS Statistics 24.0. Gray matter thickness and T1, T2, proton density, and perivascular space values were calculated from three-dimensional magnetization-prepared rapid acquisition gradient echo, magnetic resonance image compilation and diffusion tensor imaging sequences, respectively, using image data analysis software.
RESULTS
Compared with healthy controls, patients with chronic insomnia, aggravation of chronic insomnia, and new-onset insomnia had significantly higher Self-rating Anxiety Scale and Self-rating Depression Scale scores post-Omicron infection. Compared with healthy controls, the gray matter thickness was significantly reduced in the left medial orbitofrontal, lingual, pericalcarine and right lateral occipital lobes and significantly increased in the left inferior parietal and right superior parietal lobes in the patients with chronic insomnia post-Omicron infection. The individuals with good sleep quality had no change in sleep status after infection; significantly reduced gray matter thickness of the left medial orbitofrontal, cuneus, lingual and right pericalcarine; and increased gray matter thickness in the left inferior parietal, supramarginal, and bilateral superior parietal regions compared with healthy controls. Analyses showed a reduced gray matter thickness in patients with chronic insomnia compared with those with an aggravation of chronic insomnia post-Omicron infection, and a reduction was found in the right medial orbitofrontal region (mean [SD], 2.38 [0.17] vs. 2.67 [0.29] mm; P < 0.001). Compared with patients with chronic insomnia, patients with an aggravation of chronic insomnia post-Omicron infection showed a significant decrease in T1 values (left occipital and right olfactory and temporal lobes) and an increase in T2 values (left occipital and parietal and right precuneus lobes) and proton density values (bilateral frontal and right occipital and precuneus lobes). New-onset insomnia patients showed reduced gray matter thickness in the right pericalcarine (mean [SD], 1.62 [0.16] vs. 1.50 [0.15] mm; P < 0.001), and they had significantly decreased proton density values (right lingual, fusiform, parietal and temporal lobes) compared to individuals with good sleep quality, who showed no change in sleep status after infection. In new-onset insomnia patients post-Omicron infection, the thickness in the right pericalcarine was negatively correlated with the Self-rating Anxiety Scale (r = -0.538, P = 0.002, PFDR = 0.004) and Self-rating Depression Scale (r = -0.406, P = 0.026, PFDR = 0.026) scores.
CONCLUSIONS AND RELEVANCE
In summary, changes in gray matter thickness after Omicron infection were similar in chronic insomnia patients and healthy people, but there were significant differences in gray matter thickness and T1, T2, and proton density values in patients with different sleep qualities. These findings help us understand the pathophysiological mechanisms involved when Omicron invade the nervous system and induce various forms of insomnia after infection. In the future, we will continue to pay attention to the dynamic changes in the brain related to insomnia caused by Omicron infection.