COVID-19 Neurology: German Study Shows That Autoantibodies From The Cerebrospinal Fluid Targets The Brain In Certain COVID-19 Patients
: German researchers from Charité - Universitätsmedizin Berlin have shown that the neurological symptoms observed in some COVID-19 patients may be caused by autoantibodies targeting the brain.
The research team says that although some autoantibodies still need to be identified, they may at least partly explain the multiple organ disease that can occur in COVID-19 patients and help to inform immunotherapy decisions in certain cases.
The research findings that are undergoing peer-review are published on a preprint server. https://www.medrxiv.org/content/10.1101/2020.07.01.20143214v1.full.pdf
It has been observed that numerous patients with COVID-19 develop neurological symptoms, which may range from mild such as a reduced sense of smell to severe symptoms such as myoclonus (sudden involuntary muscle spasms).
Experts have debated whether such symptoms may be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting the brain.
In most patients who develop neurological symptoms however, SARS-CoV-2 is not detected in the cerebrospinal fluid (CSF). This suggests that other cellular or humoral mechanisms may be involved, including autoimmunity.
Past studies have suggested that certain viruses can lead to autoimmune encephalitis, with examples including HIV, adenovirus, and hepatitis C.
Dr Christiana Franke from the Department of Neurology and Experimental Neurology at Charité - Universitätsmedizin Berlin and colleagues recently tested whether autoantibodies were present in eleven patients with severe COVID-19 and unexplained neurological symptoms.
In the period between March and May 2020, the team assessed a large panel of antineuronal and anti-glial autoantibodies using serum and CSF samples from intensive care patients with symptoms including delirium, epileptic seizure, dystonia, and myoclonus.
The study team reports that no SARS-CoV-2 was detected in any of the CSF samples.
Cerebrospinal fluid or CSF inflammation was indicated in most patients, and all had increased CSF levels of neurofilament light chain (a biomarker for axonal damage).
Dr Franke told Thailand Medical News, “Elevated NFL levels might reflect direct tissue destruction from viral replication or from inflammatory damage. Whether this is a transient elevation or a continuous transformation into a degenerative phenotype is yet to be determined.”
It was observed that all patients had anti-neuronal antibodies in their serum or autoantibodies in their CSF that target surface antigens known to be involved in central nervous system disease.
Interestingly, among these antigens were well-established proteins such as the NMDA receptor and myelin antigens.
The study team said that one patient with a high level of serum IgG autoantibodies against NMDA receptors required cardiopulmonary resuscitation. The raised IgG level may have reflected NMDA receptor encephalitis, which often causes arrhythmia and autonomic dysfunctions.
In order to test CSF for anti-neuronal autoantibodies not routinely included in clinical assays, the team performed indirect immunofluorescence on mouse brain sections. Staining patterns showed that most patients exhibited strong immunoglobulin G (IgG) binding. The patterns showed specificity for the hippocampus, olfactory bulb, vessel endothelium, astrocytic proteins, and the neuropil of basal ganglia.
Dr Franke added, “The high frequency of CSF anti-neuronal and anti-glial autoantibodies is remarkable, as is the confinement to specific immunofluorescence patterns. Although more than one patient each had IgG autoantibodies targeting neuropil, astrocytes or medium-sized blood vessels, it will require larger patient cohorts for linking a given autoantibody pattern to clinical symptoms.”
Recent studies have demonstrated that some viral infections can lead to secondary autoimmune encephalitis, including HIV, hepatitis C Epstein-Barr virus, human herpes virus, enterovirus, and adenovirus.
The present findings suggest that SARS-CoV-2 is no exception to this general principle.
The study team said that the retrospective nature of the study means the findings could not be used to guide decisions about immunotherapy for patients.
Improvements however have been reported for some COVID-19 patients with encephalitis after they received steroids. This suggests that patients with CSF autoantibody-positive COVID-19 may benefit from immunotherapy in the future.
Dr Franke further added, “The high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms. While several underlying autoantigens still await identification in future studies, the presence of autoantibodies may explain some aspects of multi organ disease in COVID-19 and can guide immunotherapy in selected cases.”
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