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Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Young et al., 2021
https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00116-6
Highlights
Summary
COVID-19 patients frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single cell RNA-seq and cytokine analyses of CSF and blood from COVID-19 patients with neurological symptoms, we find compartmentalized, CNS specific T cell activation and B cell responses. All COVID-19 cases had CSF anti-SARS-CoV-2 antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are found only during brain infection, and are not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from a COVID-19 patient, and find that these mAbs target both anti-viral and anti-neural antigens—including one mAb that reacted to both spike protein and neural tissue. Overall, CSF IgG from 5/7 patients contains anti-neural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of COVID-19 patients and suggests a role for autoimmunity in neurologic sequelae of COVID-19.
CNS of COVID-19 patients with neurological symptoms
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00116-6
Highlights
- Immune cell scRNA-seq showed divergent T cell activation in the CNS during COVID-19
- COVID-19 patients had a compartmentalized cytokine response in the CNS
- All COVID-19 patients had anti-SARS-CoV-2 antibodies in their CSF
- Five out of seven COVID-19 patients had anti-neural autoantibodies in their CSF
Summary
COVID-19 patients frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single cell RNA-seq and cytokine analyses of CSF and blood from COVID-19 patients with neurological symptoms, we find compartmentalized, CNS specific T cell activation and B cell responses. All COVID-19 cases had CSF anti-SARS-CoV-2 antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are found only during brain infection, and are not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from a COVID-19 patient, and find that these mAbs target both anti-viral and anti-neural antigens—including one mAb that reacted to both spike protein and neural tissue. Overall, CSF IgG from 5/7 patients contains anti-neural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of COVID-19 patients and suggests a role for autoimmunity in neurologic sequelae of COVID-19.
CNS of COVID-19 patients with neurological symptoms
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
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