key: cord-0700280-g2mg88qe authors: Freire, Mayka; Andrade, Ariadna; Sopeña, Bernardo; Lopez-Rodriguez, Maria; Varela, Pablo; Cacabelos, Purificación; Esteban, Helena; González-Quintela, Arturo title: Guillain Barré syndrome associated with COVID-19- lessons learned about its pathogenesis during the first year of the pandemic, a systematic review date: 2021-06-10 journal: Autoimmun Rev DOI: 10.1016/j.autrev.2021.102875 sha: 42e898db799b5cd30b1fe275824ff678a5934394 doc_id: 700280 cord_uid: g2mg88qe nan diagnostic criteria of the GBS Classification Group (8) ; SARS-CoV-2 infection confirmed by nasopharyngeal reverse transcription polymerase chain reaction, antigen-detecting rapid diagnostic tests or serum antibody test; Detailed individual clinical description; A minimum of 6/8 points using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports and for Case Series studies (9, 10) . Finally, we selected 82 full text access articles with information about 104 clinical cases ( Table 1) to which we added our own case (Patient 32). We searched suggestive features of the three pathogenic pathways proposed to neurologic damage in COVID-19 so far (11, 12) : direct damage, dysregulated inflammatory response and antibody-mediated injury (Fig. 1) . Direct damage: As seen in some viral infections such as poliovirus, enterovirus D68, cytomegalovirus, or other human coronaviruses, SARS-Cov-2 has neuroinvasive capacity (12, 13) . The proposed access routes have been through circulation, the blood-brain barrier, or retrograde axonal transport, through the olfactory nerve or the enteric nervous system (12) . Endothelium, glial cells, and neurons express angiotensinconverting enzyme receptor 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), both necessary for the virus to get into the cells (14) . A post mortem study found SARS-CoV-2 RNA in neuroanatomical areas receiving olfactory tract projections (15) . However, PCR in CSF for COVID -19 virus was negative in all reported cases of GBS ( Table 1) , suggesting no intrathecal viral replication. Furthermore, a recent systematic review and meta-analysis showed that no study detected live SARS-COV-2 in various body fluids beyond day 9 of illness (16) and yet the median days of infection until the debut of GBS in the actual review has been 11 days. Dysregulated inflammatory response: In the "inflammatory phase" of COVID-19 infection, which characteristically begins throughout the second week of infection, elevated IL-2, IL-2R, IL-6, IL-10, IFN-γ, TNF-α, CCL2, procalcitonin, CRP, erythrocyte sedimentation rate and white blood cell, are characteristic (17) . In 2005, brain In conclusion, the absence of autoantibodies in most GBS cases associated with SARS-CoV2 infection, would force us to think about pathogenic mechanisms other than molecular mimicry. Both the short of the interval of days between the onset of COVID-19 and the neurological symptoms, and the high proportion of patients with serum elevation of inflammation markers at the beginning of neurological symptoms, support the hypothesis that cell-mediated immunity could play a role, as previously proposed for GBS related to Zika. 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Front Neurol. 2020;11:909. -: information not available; 1 1: uncomplicated disease, 2: mild pneumonia, 3: respiratory distress, 4: septic shock; 2 Days from onset of COVID-19 symptoms to onset of GB symptoms; 3 According to diagnostic criteria for GBS, MFS and their subtypes of the GBS Classification Group (8).; 4 JBI F: female; M: male; BWDP: bifacial weaknees whit distal parestesias; PCBW: pharyngeal-cervical-brachial weakness; AMSAN: acute motor-sensory axonal neuropathy; AIDP: Acute inflammatory demyelinating polyneuropathy; AMAN: acute motor axonal neuropathy Neg: negative; Pos: positive Polymerase chain reaction detection of SARS-Cov-2 in cerebrospinal fluid; DD: Ddimer; CRP: c-reactive protein; ESR: erythrocyte sedimentation rate Lopinavir/ritonavir; NE: not specified; HCQ: Hydroxychloroquine; CXM: ceftriaxone; AZM: azithromycin; MP: methylprednisolone; TCZ: tocilizumab; DOX: doxycycline; DXM: dexamethasone; Ig iv: intravenous immunoglobulins