Abstract

Background: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the structural changes in the neurological system after infection. We aimed to identify the existence of potential brain structural changes related to SARS-CoV-2. Methods: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 48 recovered COVID-19 patients (60.42% male; mean age=47.81 ± 19.51) and 31 age-matched healthy controls (29.03% male; age=43.45 ± 13.6). Registered fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) were quantified for DTI, and a brain score system was introduced. Voxel-based Morphometry (VBM) and DTI metrics were compared using ANCOVA. Independent t-test and Spearman correlation were conducted to assess the relationships among imaging indices, brain scores and clinical information. Findings: COVID-19 patients had higher gray matter volumes (GMV) in hippocampus and Heschl’s gyrus, and higher white matter volumes (WMV) in corona radiata and tapetum. The left paracentral lobule was found to have significantly lower FA, higher MD, AD and RD values when compared with healthy controls. COVID-19 patients also had lower global MD and RD values, as well as lower brain scores of FA-GM, MD-GM, and MD-WM. MD values in the right corona radiata and external capsule were positively related to LDH level (r = 0.428, 0.417). Interpretation: Study findings reveal possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting neuro-invasion potential of SARS-CoV-2. Funding: This project was supported by Shanghai Natural Science Foundation (Grant No. 18ZR1405700), Youth Program of National Natural Science Foundation of China (Fund No. 81901697), Shanghai Sailing Program (Grant No. 18YF1403000), Shanghai Science and Technology Development (Fund No. 19511121204), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01) and ZJ Lab.Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: This was a prospective study, which was approved by the local ethics committee (No.20200616017) and written informed consent was obtained from each participant.

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