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

Shilan Chen; Jianhao Liang; Dingqiang Chen; Qiyuan Huang; Kaijian Sun; Yuxia Zhong; Baojia Lin; Jingjing Kong; Jiaduo Sun; Chengfang Gong; Jun Wang; Ya Gao; Qingguo Zhang; Haitao Sun

doi:10.1016/j.bbi.2023.10.016

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

Brain Behav Immun. 2024 Jan:115:209-222. doi: 10.1016/j.bbi.2023.10.016. Epub 2023 Oct 17.

Authors

Shilan Chen¹, Jianhao Liang¹, Dingqiang Chen², Qiyuan Huang², Kaijian Sun³, Yuxia Zhong², Baojia Lin⁴, Jingjing Kong², Jiaduo Sun⁵, Chengfang Gong¹, Jun Wang³, Ya Gao⁶, Qingguo Zhang⁷, Haitao Sun⁸

Affiliations

¹ Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China; Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
² Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
³ Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
⁴ Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
⁵ Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China; Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.
⁶ Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: smugaoya_729@163.com.
⁷ Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China. Electronic address: zjyyzqg@126.com.
⁸ Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Guangdong Provincial Clinical Research Center for Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China; Neurosurgery Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China. Electronic address: 2009sht@smu.edu.cn.

PMID: 37858739
DOI: 10.1016/j.bbi.2023.10.016

Abstract

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.

Keywords: Biomarker; COVID-19; Cerebrospinal fluid; Multi-omics; Neuro-PASC; SARS-CoV-2.

MeSH terms

COVID-19*
Disease Progression
Humans
Post-Acute COVID-19 Syndrome
Proteomics
SARS-CoV-2

Substances

safingol