Literature analysis and translation by: Claudia Foray and Sonia Fanelli Reviewed by: Alda Rocca
COVID-19 infection is usually associated with fever and respiratory symptoms. Neurological aspects related to SARS-CoV-2 are still poorly understood, but it is now clear that the virus affects not only the broncho-pulmonary system, but also other body compartments, including the central and peripheral nervous system (CNS, PNS). In this review, we report several subtypes of neurological disorders, observed in SARS-CoV-2 patients, grouped under the name of Guillain-Barré syndrome.
Some neurological manifestations of COVID-19 are becoming increasingly recognized and include impairment of smell and taste, acute cerebrovascular disease and encephalopathy. Guillain-Barré syndrome (GBS) is an acute/subacute immune-mediated polyradiculoneuropathy, characterized by varying degrees of limbs or cranial-nerves weakness, loss of deep tendon reflexes, sensory and dysautonomic symptoms due to peripheral nerves and roots demyelination and/or axonal damage. Several subtypes are delineated: acute inflammatory demyelinating poly‐radiculo‐neuropathy (AIDP), acute axonal motor neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN), Miller‐Fisher syndrome (MFS) and Bickerstaff encephalitis. GBS can appear following a viral or bacterial infection, including influenza, hepatitis, HIV, Zika virus, C. jejuni and M. pneumoniae.
Zhao et al. were the first to describe a COVID-19 related GBS case1 and others have been reported since the outbreak of SARS-CoV-2 in Europe and Asia2, 3, 4. Gupta and colleagues highlighted some important differences in the presentation of typical GBS and the COVID-19 related GBS5, as also reported by other groups6, 7, 8, 9. Typical GBS can affect all age groups and, in 25% of cases, severe respiratory failure or gastrointestinal symptoms occur as initial symptoms. In the majority of COVID-19 related GBS patients, the syndrome began after COVID‐19 infection. Latency between onset of GBS and COVID‐19 infection ranged from 3 to 23 days. Three studies reported that patients were asymptomatic when diagnosed with GBS but resulted positive for COVID-19 after swab test7, 11, 8. Elderly male patients were more frequently affected than women and younger individuals. Upper and/or lower extremity weakness and paresthesias were common symptoms, together with ataxia and areflexia. Moreover, patients with COVID-19-related GBS frequently had a severe disease with respiratory failure due to lobar or interstitial pneumonia. The majority of SARS-CoV-2-related GBS patients were diagnosed with AIDP, followed by AMAN and AMSAN. Two cases were diagnosed with COVID-19 related GBS with atypical features, one overlapped with MFS and one in association with severe autonomic neuropathy10. In some cases, MRI showed enhancement of the caudal nerve roots or facial nerve. In some patients, symptoms rapidly progressed to tetraplegia requiring mechanical ventilation. Lymphopenia and thrombocytosis were common among the majority of patients, as well as the absence of COVID-19 and anti-ganglioside antibodies in the CSF. Most COVID-19-related GBS patients were treated with hydroxychloroquine, azithromycin, lopinavir and ritonavir in addition to intravenous immunoglobulin (IVIG). In most cases, the response to IVIG was favourable and dependent on comorbidities, but several patients showed poor outcome with long ICU stay, residual paresis and dysphagia.
Taken together, all these findings show that the causal association between GBS and COVID-19 is highly probable. Absence of the virus in the CSF suggests that GBS is not triggered by a direct viral attack against the nerve roots but rather by an immune‐mediated mechanism. Moreover, COVID-19 may manifest primarily with neurological signs in patients with an acute paralytic disease like GBS, even without fever or any systemic symptoms. Emerging data indicate that COVID-19 can trigger not only GBS but other autoimmune neurological diseases, such as necrotizing autoimmune myositis (NAM) and acute disseminated encephalomyelitis, necessitating vigilance for early diagnosis and therapy initiation12.
 Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barrè syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol. 2020;19:383-384.
 Toscano G, Palmerini F, Ravaglia S, et al. Guillain–Barré Syndrome Associated with SARS-CoV-2. N Engl J Med. April 2020.
 Padroni M, Mastrangelo V, Asioli GM, et al. Guillain-Barré syndrome following COVID-19: new infection, old complication? J Neurol. 2020;267(7):1877-1879.
 Ottaviani D, Boso F, Tranquillini E, et al. Early Guillain-Barré syndrome in coronavirus disease 2019 (COVID-19): a case report from an Italian COVID-hospital. Neurol Sci. 2020;41(6):1351-1354.
 Gupta A, Paliwal VK, Garg RK. Is COVID-19-related Guillain-Barré syndrome different?. Brain Behav Immun. 2020;87:177-178.
 Finsterer J, Scorza FA, Ghosh R. COVID-19 polyradiculitis in 24 patients without SARS-CoV-2 in the cerebro-spinal fluid [published online ahead of print, 2020 Jun 4]. J Med Virol. 2020;10.1002/jmv.26121.
 Chan JL, Ebadi H, Sarna JR. Guillain-Barré Syndrome with Facial Diplegia Related to SARS-CoV-2 Infection [published online ahead of print, 2020 May 29]. Can J Neurol Sci. 2020;1-3.
 Lascano AM, Epiney JB, Coen M, et al. SARS-CoV-2 and Guillain-Barré syndrome: AIDP variant with favorable outcome [published online ahead of print, 2020 Jun 1]. Eur J Neurol. 2020;10.1111/ene.14368.
 Sancho-Saldaña A, Lambea-Gil Á, Liesa JLC, et al. Guillain-Barré syndrome associated with leptomeningeal enhancement following SARS-CoV-2 infection. Clin Med (Lond). 2020;20(4):e93-e94.
 Assini A, Benedetti L, Di Maio S, Schirinzi E, Del Sette M. New clinical manifestation of COVID-19 related Guillain-Barrè syndrome highly responsive to intravenous immunoglobulins: two Italian cases [published correction appears in Neurol Sci. 2020 Jun 8;:]. Neurol Sci.
 Su XW, Palka SV, Rao RR, Chen FS, Brackney CR, Cambi F. SARS-CoV-2-associated Guillain-Barré syndrome with dysautonomia. Muscle Nerve. 2020;62(2):E48-E49.
 Dalakas MC. Guillain-Barré syndrome: The first documented COVID-19-triggered autoimmune neurologic disease: More to come with myositis in the offing. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e781. Published 2020 Jun 9.