Abstract

BackgroundCOVID-19 intensive care patients can present with neurological syndromes, usually in the absence of SARS-CoV-2 in cerebrospinal fluid (CSF). The recent finding of some virus-neutralizing antibodies cross-reacting with brain tissue suggests the possible involvement of specific autoimmunity. DesignBlood and CSF samples from eleven critically ill COVID-19 patients presenting with unexplained neurological symptoms including myoclonus, oculomotor disturbance, delirium, dystonia and epileptic seizures, were analyzed for anti-neuronal and anti-glial autoantibodies. ResultsUsing cell-based assays and indirect immunofluorescence on unfixed murine brain sections, all patients showed anti-neuronal autoantibodies in serum or CSF. Antigens included intracellular and neuronal surface proteins, such as Yo or NMDA receptor, but also various specific undetermined epitopes, reminiscent of the brain tissue binding observed with certain human monoclonal SARS-CoV-2 antibodies. These included vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb. ConclusionThe high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms, in particular to hyperexcitability (myoclonus, seizures). Several underlying autoantigens and their potential molecular mimicry with SARS-CoV-2 still await identification. However, autoantibodies may already now explain some aspects of multi-organ disease in COVID-19 and can guide immunotherapy in selected cases.

Highlights

  • Clinical neurological symptoms in COVID-19 A broad variety of neurological symptoms has been observed in COVID-19 patients

  • We report autoantibody findings in eleven critically ill COVID-19 patients presenting with a variety of neurological symptoms with unexplained etiology

  • Clinical improvement of COVID-19 patients with Guillain-Barré syndrome (GBS) has been reported after therapy with intravenous immunoglobulins[6] and after steroids in COVID-19 patients with encephalitis[7], indicating that immunotherapy should be considered in future cases of cerebrospinal fluid (CSF) autoantibody-positive COVID-19 patients

Read more

Summary

Introduction

Clinical neurological symptoms in COVID-19 A broad variety of neurological symptoms has been observed in COVID-19 patients. Neurological syndromes in association with SARS-CoV-2 include many autoimmune diseases, such as Guillain-Barré syndrome (GBS), Miller-Fisher syndrome (MFS), polyneuritis cranialis, meningitis, encephalitis, stroke, epilepsy and myopathy[2,3]. It is debated whether direct virus invasion into the brain can cause pathology, SARS-CoV-2 has been detected only scarcely in cerebrospinal fluid (CSF)[3]. Cellular or humoral autoimmunity might contribute to neurological symptoms, similar to other viral diseases. We examined the presence of a large panel of antineuronal and anti-glial autoantibodies in serum and CSF of COVID-19 patients with predominant neurological symptoms

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call