Study: Cerebrospinal fluid biomarkers in SARS-CoV-2 patients with acute neurological syndromes. Image Credit: Kateryna Kon / Shutterstock

Elevated CSF biomarkers of neuroinflammation in NeuroCOVID patients

The association of SARS-CoV-2 infection (NeuroCOVID) with nervous system damage is not clearly understood. The non-exclusive mechanisms that may lead to NeuroCOVID may include invasion of the brain by the virus along the cranial nerve pathways or disruption of the blood barrier (BBB) ​​and compartmentalized or deleterious systemic immune response in the central nervous system (CNS). Understanding these mechanisms is vital for developing therapeutic targets and strategies for preventing long-term neurological effects in NeuroCOVID patients.

Study: CSF biomarkers in SARS-CoV-2 patients with acute neurological syndromes† ​​​​​​​Image credit: Kateryna Kon / Shutterstock

NeuroCOVID may increase the risk of developing a neurodegenerative disease or accelerate its progression. Several factors can trigger a neurodegenerative cascade in NeuroCOVID patients, including the vulnerability of some brain regions to SARS-CoV-2 infection and dysregulation of genes important for neuronal survival by SARS-CoV-2, as well as dysregulation of the gut microbiota by SARS -CoV-2 infection and its impact on the brain. Other factors leading to depression, prolonged intensive care (ICU) stay, severe sepsis, or post-traumatic stress may also be associated with the risk of cognitive decline after SARS-CoV-2 infection.

Most of the previous studies examining the effects of SARS-CoV-2 infection on the CNS pointed to neurodegeneration, acute neuronal injury or neuroinflammation, while only a few focused on biomarkers characterizing these different mechanisms. Therefore, further studies are needed with large, well-characterized NeuroCOVID patients to understand and prevent the pathogenesis of CNS damage.

A new research paper, which is being reviewed in the Molecular Neurobiology magazine and currently available on the Research Square* preprint server, studied several biomarkers associated with neuronal injury, neuroinflammation and neurodegeneration in NeuroCOVID adults experiencing CNS syndrome during acute SARS-CoV-2 infection.

About the study

The study involved 24 COVID-19-confirmed patients who had neurological symptoms between March 2020 and June 2021. Confirmation of SARS-CoV-2 infection was performed using real-time protein chain reaction (RT-PCR).

Data on the patients’ medical histories, along with neurophysiological recordings and clinical, neuroradiological and biological examinations, were collected during their hospital stay. Patients were classified as having meningoencephalitis or encephalopathy and disease severity was defined as moderate, mild, severe, or critical.

The plasma and cerebrospinal fluid (CSF) were screened to detect any co-infections. Finally, CSF biomarkers for neurodegeneration and neuronal injury and CSF neopterin for neuroinflammation were quantified.

Study findings

The results reported that the median age of the patients was 62 years, that no patient had a history of neurological disorders and that most of the patients were male. Encephalopathy was reported to be the primary neurological syndrome, although eight patients developed movement disorders and five suffered strokes. Disease severity was found to be moderate, severe, or critical, and patients hospitalized in ICU were shown to benefit from mechanical ventilation.

The patients reported a lumbar puncture within 5 days of the onset of neurological symptoms. Only CSF pleocytosis, albumin ratio, and protein levels were found to be elevated in patients with meningoencephalitis, while no other difference in biomarkers was observed. Isoelectric focus patterns 2 and 3 were observed in 50% of patients with severe illness, 25% of patients with moderate illness and 70% of patients with critical illness. In addition, the level of CSF-neopterin was found to be elevated in 75% of the patients.

CSF neurofilament light chain (NfL) levels were found to be higher in patients, while no correlation was found with age, length of ICU stay and lumbar puncture. Total tau protein levels were also found to be elevated and a positive correlation between NfL CSF and T-tau levels was also observed.

Level of CSF NfL in NeuroCOVID group and controls Box plots of cerebrospinal fluid (CSF) neurofilament light chain (NfL) in NeuroCOVID (n=19, 13 encephalopathies in blue and six meningoencephalitis in red) and controls from non-COVID patients with psychiatric disorders (n=20, in black)

Level of CSF NfL in NeuroCOVID group and controls Box plots of cerebrospinal fluid (CSF) neurofilament light chain (NfL) in NeuroCOVID (n=19, 13 encephalopathies in blue and six meningoencephalitis in red) and controls from non-COVID patients with psychiatric disorders (n=20, in black)

The Aß1-42 peptide was found to be low in 11 patients, two of whom had meningoencephalitis and nine had encephalopathy. The CSF NfL concentration was also found to be elevated in these patients; however, the tau protein levels were found to be normal. No patient had a typical CSF pattern indicative of Alzheimer’s disease.

Therefore, the present study demonstrated the elevation of CSF biomarkers of neuronal injury and neuroinflammation in severe NeuroCOVID patients. This could lead to neuronal damage and disruption of the processing of amyloid precursor peptides. Therefore, anti-inflammatory drugs are essential during the early stages of the disease. Further studies are needed to confirm whether SARS-CoV-2-induced neuronal damage can lead to a chronic neurodegenerative process.

*Important announcement

Research Square publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, should guide clinical practice/health-related behavior or be treated as established information.[if–>

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