Cerebrospinal fluid metabolomic and proteomic characterization of neurologic post-acute sequelae of SARS-CoV-2 infection

• Published in: Brain, behavior, and immunity Vol. 115; pp. 209 - 222
• Main Authors: Chen, Shilan, Liang, Jianhao, Chen, Dingqiang, Huang, Qiyuan, Sun, Kaijian, Zhong, Yuxia, Lin, Baojia, Kong, Jingjing, Sun, Jiaduo, Gong, Chengfang, Wang, Jun, Gao, Ya, Zhang, Qingguo, Sun, Haitao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.01.2024
• Subjects: Biomarker; Cerebrospinal fluid; COVID-19; Multi-omics; Neuro-PASC; SARS-CoV-2; COVID-19; SARS-CoV-2; Biomarker; Neuro-PASC; Cerebrospinal fluid; Multi-omics
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2023.10.016

•The metabolomics and proteomics of CSF exhibit significant disparities between neuro-PASC patients and healthy volunteers.•Elevated sphinganine and ST1A1, disrupted sphingolipid metabolism and attenuated inflammatory response may lead to neuro-PASC.•Decreased 7,8-dihydropterin and upregulated steroid hormone biosynthesis may be a reparative mechanism for neuro-PASC.•Biomarker cohort consisting of sphinganine, 7,8-dihydroneopterin, and ST1A1 shows promising efficacy in diagnosing neuro-PASC. The mechanism by which SARS-CoV-2 causes neurological post-acute sequelae of SARS-CoV-2 (neuro-PASC) remains unclear. Herein, we conducted proteomic and metabolomic analyses of cerebrospinal fluid (CSF) samples from 21 neuro-PASC patients, 45 healthy volunteers, and 26 inflammatory neurological diseases patients. Our data showed 69 differentially expressed metabolites and six differentially expressed proteins between neuro-PASC patients and healthy individuals. Elevated sphinganine and ST1A1, sphingolipid metabolism disorder, and attenuated inflammatory responses may contribute to the occurrence of neuro-PASC, whereas decreased levels of 7,8-dihydropterin and activation of steroid hormone biosynthesis may play a role in the repair process. Additionally, a biomarker cohort consisting of sphinganine, 7,8-dihydroneopterin, and ST1A1 was preliminarily demonstrated to have high value in diagnosing neuro-PASC. In summary, our study represents the first attempt to integrate the diagnostic benefits of CSF with the methodological advantages of multi-omics, thereby offering valuable insights into the pathogenesis of neuro-PASC and facilitating the work of neuroscientists in disclosing different neurological dimensions associated with COVID-19.