Neurological

Understand the pathogenesis of neurological impairment in patients with COVID-19

Although encephalopathies in patients with severe SARS-CoV-2 infection are not due to severe viral infections in the brain or cytokine storm leakage from the periphery to the central nervous system (CNS), there is a strong association between encephalopathies and impairment of the blood brain barrier (BBB) , according to study results published in Neurology Neuroimmunology & Neuroinflammation.

Although COVID-19 outbreaks have often been linked to neurological disorders and a range of neurological complications, there are still few hypotheses that clearly explain these complications. However, the response of encephalitis and encephalopathies to corticosteroids suggests that immune mechanisms may be involved.

In order to better understand the underlying mechanisms of neurological symptoms associated with SARS-CoV-2 infection, a team of researchers in Switzerland carried out a cross-sectional study to determine whether neurological symptoms were directly caused by or through SARS-CoV-2 infection a systemic or local pro-inflammatory mediator.

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Using the quantitative reverse transcription polymerase chain reaction (RT-qPCR), the study researchers tested 77 patients for SARS-CoV-2 ribonucleic acid (RNA), SARS-CoV-2-specific antibodies and for 49 cytokines, chemokines and growth factors in the Cerebrospinal fluid (CSF). 22 patients had COVID-19 and 55 patients were included in the control cohort.

Of the 22 patients with COVID-19, 13 patients were admitted to the intensive care unit (ICU) and 9 patients required mechanical ventilation. 11 of the 13 patients admitted to the intensive care unit presented with encephalopathy. Of the 8 patients who underwent a nerve conduction study, 6 had confirmed critical myopathy or polyneuropathy. No significant magnetic resonance imaging abnormalities were observed. In addition, 7 of the 8 electroencephalography (EEG) tests showed abnormalities.

Although all RT-qPCR results for the detection of SARS-CoV-2 in the CSF were negative, antibodies against SARS-CoV-2 were detected in the CSF in 10 of 21 patients with COVID-19. None of the control patients had detectable SARS-CoV-2 antibodies in the CSF (P <0.0001).

In addition, the antibody index was elevated in the majority of patients with severe COVID-19 (5 out of 8 patients; 62.5%); this suggested the intrathecal synthesis of antibodies against SARS-CoV-2 in some patients.

Compared to patients with moderate COVID-19, those with severe COVID-19 had a higher percentage of elevated albumin levels (P = .049). Consequently, study researchers assessed the relationship between the albumin ratio and CSF levels of CXC-motif chemokine ligand 8 (CXCL8), CC-motif chemokine ligand 2 (CCL2), and vascular endothelial growth factor A (VEGF-A) .

The results showed that patients with increased albumin ratios had significantly more CXCL8 in the CSF. While the VEGF-A levels in these patients were also almost significant (P = .059), the CCL2 levels showed no difference.

The CXCL8 CSF / serum index was increased in 6 of 9 patients with severe COVID-19 and in 0 of 5 patients with milder forms (P = .0310), suggesting intrathecal synthesis.

“[O]Our study identifies a possible mechanism by which the activation of neurovascular unit cells as a result of peripheral inflammation and / or hypoxia leads to a barrier disorder. The fact that [COVID-19-associated] Corticosteroid-responsive encephalopathies support this hypothesis, ”the study’s researchers concluded.

reference

Bernard-Valnet R, Perriot S, Canales M, et al. Encephalopathies associated with severe COVID-19 show changes in the neurovascular unit with no evidence of severe neuroinflammation. Neurol Neuroimmunol Neuroinflamm. 2021; 8 (5): e1029. doi: 10.1212 / NXI.0000000000001029

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