Brain, behavior, and immunityOct 20, 2023

Chemical and protein changes in spinal fluid linked to long-term brain symptoms after COVID-19

Updated Apr 6, 2026

Abstract

Proteomic and metabolomic analyses of cerebrospinal fluid from 21 neuro-PASC patients revealed 69 differentially expressed metabolites and six proteins compared to healthy individuals.

Elevated sphinganine and ST1A1, along with a disorder in sphingolipid metabolism, may contribute to neuro-PASC.
Attenuated inflammatory responses could also be involved in the occurrence of neuro-PASC.
Decreased levels of 7,8-dihydropterin and increased steroid hormone biosynthesis may aid in the repair process.
A biomarker cohort including sphinganine, 7,8-dihydroneopterin, and ST1A1 may have diagnostic value for neuro-PASC.

Simplified

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.

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Declaration of Competing Interest 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.

PubMed

Chemical and protein changes in spinal fluid linked to long-term brain symptoms after COVID-19

Abstract

Full Text

Funding

Competing interests

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Abstract

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Funding

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