Cerebrospinal Fluid Proteomic Profiling Reveals Proteins Associated with Neuroinflammatory Response in COVID-19 Patients

TL;DR

This study identifies proteins in cerebrospinal fluid linked to neuroinflammation in critically ill COVID-19 patients, offering insights into neurological complications.

Contribution

The study reveals novel proteomic signatures in CSF associated with neuroinflammatory and coagulation responses in severe COVID-19.

Findings

Proteins involved in coagulation and immune responses were significantly upregulated in CSF of COVID-19 patients.

Antioxidant defense and neural maintenance proteins were significantly downregulated in CSF of COVID-19 patients.

Functional analysis highlighted enriched pathways related to hemostasis, immune regulation, and neuroinflammation.

Abstract

The COVID-19 pandemic has highlighted the diverse clinical
manifestations
of SARS-CoV-2 infection, including neurological complications. This
study investigates cerebrospinal fluid (CSF) proteomic profiles to
identify proteins associated with neuroinflammatory processes in COVID-19.
CSF samples from 11 critically ill patients and 5 COVID-19-negative
controls were analyzed using high-resolution liquid chromatography-tandem
mass spectrometry. A total of 203 proteins were identified, of which
76 exhibited differential expression peptides (DEPs). Proteins involved
in coagulation (fibrinogen alpha and beta chains, prothrombin) and
immune responses (complement cascade components, immunoglobulin heavy
constant gamma, kappa, and lambda subunits) were significantly upregulated
in COVID-19 patients. In contrast, proteins involved in antioxidant
defense (e.g., superoxide dismutase) and neural maintenance (e.g.,
neural cell adhesion molecule 1, Neuronal cell adhesion molecule)
were significantly downregulated. Functional annotation revealed enriched
pathways associated with hemostasis, immune regulation, and neuroinflammatory
responses. Protein–protein interaction analysis highlighted
interactions among complement and coagulation cascade components,
underscoring their roles in inflammation and potential thrombotic
complications. These findings suggest that SARS-CoV-2 infection induces
significant alterations in the CSF proteome, reflecting neuroinflammatory
and oxidative stress mechanisms. Identifying these proteins and their
association with diverse pathophysiological mechanisms provides insights
into the neurological impact of COVID-19 and may serve as therapeutic
targets and potential biomarkers. Further studies are needed to validate
these findings and explore their clinical implications in post-COVID-19
neurological syndromes.

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