Guillain–Barré Syndrome in COVID-19—The Potential Role of NCAM-1 and Immunotherapy

Coronavirus disease 2019 (COVID-19) interacts with the nervous system directly and indirectly by affecting the activation of the immune system. Guillain–Barré syndrome (GBS) is triggered by an inappropriate immune system activation that overlaps with the neurotoxic mechanism of an invading pathogen. Here, we discuss the complexity of an abnormal immune system response leading to the generation of autoimmunity in the setting of acute viral infection. A 67-year-old male patient with COVID-19 developed a sensory motor acute polyneuropathy with respiratory failure. Several serum inflammatory and neurodegeneration markers were collected during hospital days 1, 3, 8, and 67 and compared to healthy individuals. Neural cell adhesion molecule 1 (NCAM-1) and neurofilament light chain (NfL) values were highly variable when compared to healthy individuals, but not to the reference COVID-19 group. We focused our attention on NCAM-1 as a possible target for antibodies directed at COVID-19 in silico.

SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

Management of Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) is the most common, immune-mediated acute polyneuropathy characterized by variable degree of motor weakness, often presenting with quadriparesis. GBS with respiratory failure requiring endotracheal intubation with mechanical ventilation is common, affecting approximately 30% of patients. In addition, they present with sensory features, cranial nerve involvement, and autonomic disturbance. The majority of GBS patients have preceding respiratory tract infection or gastroenteritis. The diagnosis of GBS is based on clinical features supported by cerebrospinal fluid (CSF) examination and nerve conduction studies. Early course of the GBS requires meticulous monitoring and early initiation of immunotherapy. Plasma exchange (PE) and intravenous immunoglobulin (IVIg) are the proven therapies, and both have been shown to be equally effective. General supportive care is an important part of management of GBS. A multidisciplinary approach to prevent and manage potential complications in rapidly progressing GBS is important to reduce morbidity and mortality.

GUILLAIN — BARRÉ SYNDROME AS A RELEVANT ISSUE OF NEUROLOGY (A LITERATURE REVIEW)

Acute infl ammatory polyneuropathy is an important research problem of modern neurology. Guillain — Barré syndrome is a severe form of acute polyneuropathy, which is based on autoimmune infl ammation of the myelin sheath of roots and peripheral nerves. Guillain — Barré syndrome is an example of one of the most severe diseases of the nervous system, in which timely diagnosis, proper therapy and qualifi ed care facilitate the achievement of the full recovery of lost functions in most patients. Following an extensive review of Russian and foreign literature, this article discusses modern concepts of Guillain — Barré syndrome, in particular questions related to its epidemiology, etiopathogenesis, classifi cation, clinical features, diagnosis, treatment and prognosis.