key: cord-1032161-11no8dsk authors: Finsterer, Josef; Scorza, Fulvio A.; Ghosh, Ritwik title: COVID‐19 polyradiculitis in 24 patients without SARS‐CoV‐2 in the cerebro‐spinal fluid date: 2020-06-12 journal: J Med Virol DOI: 10.1002/jmv.26121 sha: 469db2cf1f8eead79bcb5cd949d648f9fc67c614 doc_id: 1032161 cord_uid: 11no8dsk OBJECTIVES to summarise and discuss current knowledge about COVID-19-associated Guillain-Barre syndrome (GBS). METHOD literature review RESULTS: altogether 18 articles were found, which reported 23 patients with COVID-19-associated GBS. A further patient came to our attention by personal communication. Among these 24 included patients age ranged from 20 to 76y. There was male preponderance. Fourteen patients presented with acute inflammatory demyelinating polyneuropathy (AIDP), 4 with acute motor axonal neuropathy (AMAN), 3 with Miller-Fisher syndrome (MFS), and 2 with acute motor and sensory axonal neuropathy (AMSAN). In one patient the subtype was not specified. The cerebrospinal fluid (CSF) was tested for SARS-CoV-2 in 15 patients but was negative for the virus in all of them. Seven patients required artificial ventilation. Twenty-one patients received intravenous immunoglobulines (IVIG). Thirteen patients recovered, 6 did not, and 2 patients died. CONCLUSIONS SARS-CoV-2 can cause GBS. SARS-CoV-2-associated GBS occurs in the absence of the virus in the CSF. Clinical presentation, course, response to treatment, and outcome do not vary between SARS-CoV-2-associated GBS and GBS due to other triggers. This article is protected by copyright. All rights reserved. To the Editor, The current hostage of mankind, coronavirus disease-2019 (COVID- 19) , has not only strong political, socioeconomic, and cultural implications, but also stimulates science. Meanwhile it is common sense that the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not only affects the broncho-pulmonary system, but can be found in nearly all compartments of the body, including the central and peripheral nervous system (CNS, PNS). 1 One of the recently described manifestations in the PNS is Guillain-Barre syndrome (GBS). 2 GBS covers a group of autoimmune disorders that share a common presentation of acute/subacute, progressive poly-radiculo-neuropathy in common. 3 According to the underlying pathology, clinical presentation, and findings on nerve conduction studies (NCSs), several subtypes are delineated. These include acute, inflammatory, demyelinating poly-radiculoneuropathy (AIDP) with primarily demyelinating features and a favorable prognosis, 3 acute, axonal, motor neuropathy (AMAN) with primary axonal injury, pure motor involvement, and a worse prognosis, 3 acute, motor, sensory, axonal neuropathy (AMSAN), which shares a similar pathogenesis as AMAN but with additional sensory involvement, Miller-Fisher syndrome (MFS), characterized by ophthalmoparesis, areflexia, and ataxia, Bickerstaff encephalitis presenting similarly to MFS but additionally with impaired consciousness due to brainstem involvement, the pharyngeal-cervico-brachial variant, associated with GQ1b and GD1a antibodies and pandysautonomia, associated with GT1a antibodies. 3 The incidence of GBS ranges between 1.1 and 2.7/100 000/year. 3 This mini-review aims at summarising and discussing recent advances concerning SARS-CoV-2-induced polyradiculitis. A literature search using the search terms "SARS-CoV-2," "COVID-19," and "corona virus" together with "Guillain-Barre syndrome," "GBS," "AIDP," "AMAN," "AMSAN," "MFS," "Bickerstaff encephalitis," "pandysautonomia," and "polyradiculitis" was carried out. (Table 1) . Sex was reported in 19 patients. Thirteen patients were male and 6 were female (Table 1 ). In 22 patients GBS began after onset of clinical manifestations of COVID-19. Latency between onset of COVID-19 and GBS respectively GBS and COVID-19 was reported in 24 cases and ranged from 3 to 23 days (mean: 9.6 days). Forteen patients were diagnosed with AIDP, four with AMAN, three with MFS, and two with AMSAN. In one patient the subtype was not specified (Table 1) . (Table 1) . Twenty-one patients received intravenous immunoglobulins (IVIG), and one additionally plasmapheresis ( Table 1) . One of the Spanish patients received steroids (Table 1) . Two patients with MFS remained without therapy and recovered spontaneously (Table 1) . Seven patients required artificial ventilation (Table 1) This review shows that SARS-CoV-2 can manifest with polyradiculitis. As with non-SARS-CoV-2-associated GBS, there is a male preponderance. Elderly patients are more frequently affected than the younger generation. The most prevalent subtype of GBS is AIDP. In patients with SARS-CoV-2-associated GBS no virus is found in the CSF. In most cases the response to IVIG is favorable, and dependent on comorbidities. About one-third of the patients with SARS-CoV-2associated GBS requires mechanical ventilation. In some cases the outcome is poor or even fatal. Since most patients with SARS-CoV-2-associated GBS developed GBS on the average 10 days after the first non-neurological symptoms of the viral infection, a causal relation is quite likely. In the two patients in whom GBS developed before non-neurological manifestations of the infection developed, 2,16 the infection most likely preceded the onset of GBS as well but may have remained subclinical or gone unrecognized. An argument against a causal relation, however, is that in none of the included patients SARS-CoV-2 was found in the CSF. 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, such as antibody precipitation on myelin sheaths or axons. It is also conceivable that there is mimicry between epitopes on the surface of the virus and on membranes of motor or sensory neurons, why they are simultaneously attacked by the immune response, a similar mechanism as in GBS due to C. jejunii. Furthermore, there are indications that COVID-19 is associated with a cytokine storm and a dysregulated immune response. 21 It is also conceivable that the virus directly invades motor and sensory neurons since the virus has been found in neurons and endothelial cells of the frontal lobe. 22 There are speculations that the brain could be even a reservoir for the virus in the absence of severe clinical manifestations. 23 Whether SARS-CoV-2-associated GBS is more prevalent in patients with than without pre-existing damage of peripheral nerves remains speculative. Only one patient with diabetes was suspected to have had a premorbid neuropathy. Update on the neurology of COVID-19 Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? 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