Provisional case definitions for COVID-19-associated neurological disease
Authors: Hai-Feng Li, Hong-Jun Hao, Xiang-Jun Chen
Journal: The Lancet Neurology (2020)

In The Lancet Neurology, Mark Ellul and colleagues1Ellul MA Benjamin L Singh B et al.Neurological associations of COVID-19.Lancet Neurol. 2020; 19: 767-783Summary Full Text Full Text PDF PubMed Scopus (1372) Google Scholar propose case definitions for the association of COVID-19 with neurological diseases. We would like to discuss the practicality of their definitions and the potential causality behind the associations, through the example of Guillain-Barré syndrome. Guillain-Barré syndrome can be easily differentiated from neurovirulent neuropathies, such as West Nile virus-associated neuropathy, and there is surveillance on its incidence in several countries, which renders Guillain-Barré syndrome a good candidate for assessing the association between infection and neurological disease. Neurological disease occurring in the 6-week interval after acute infection is considered evidence for autoimmune association. However, typical acute respiratory symptoms are not always indicators of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; atypical presymptomatic or asymptomatic presentations of SARS-CoV-2 infection can occur before the onset of Guillain-Barré syndrome. Should we adopt the WHO-confirmed COVID-19 case definition1Ellul MA Benjamin L Singh B et al.Neurological associations of COVID-19.Lancet Neurol. 2020; 19: 767-783Summary Full Text Full Text PDF PubMed Scopus (1372) Google Scholar as the definition of SARS-CoV-2 infection? Moreover, should we use the screening date of a positive SARS-CoV-2 result as the onset of acute SARS-CoV-2 infection in all patients with Guillain-Barré syndrome without typical COVID-19 symptoms? A possible association differs from a probable association in the evidence of other commonly associated causes. Although Ellul and colleagues1Ellul MA Benjamin L Singh B et al.Neurological associations of COVID-19.Lancet Neurol. 2020; 19: 767-783Summary Full Text Full Text PDF PubMed Scopus (1372) Google Scholar discuss evidence from other viruses as the cause of Guillain-Barré syndrome, influenza was not listed in their proposed case definitions for COVID-19-associated neurological disease. There is robust evidence on influenza-like illnesses as triggers for Guillain-Barré syndrome, and vaccination against influenza might reduce the risk of influenza-associated Guillain-Barré syndrome.2Petráš M Lesná IK Dáňová J Čelko AM Is an increased risk of developing Guillain-Barré syndrome associated with seasonal influenza vaccination? A systematic review and meta-analysis.Vaccines (Basel). 2020; 8: 150Crossref Scopus (16) Google Scholar Early data showed a co-infection with influenza virus in about 50% of hospitalised patients with COVID-19.3Yue H Zhang M Xing L et al.The epidemiology and clinical characteristics of co-infection of SARS-CoV-2 and influenza viruses in patients during COVID-19 outbreak.J Med Virol. 2020; (published online Jun 12.)https://doi.org/10.1002/jmv.26163Crossref Scopus (117) Google Scholar Co-infection of SARS-CoV-2 also exists in influenza-like illness.4Kong WH Li Y Peng MW et al.SARS-CoV-2 detection in patients with influenza-like illness.Nat Microbiol. 2020; 5: 675-678Crossref PubMed Scopus (115) Google Scholar Therefore, influenza should be included among the possible causes of Guillain-Barré syndrome. Moreover, evaluation of the safety of a SARS-CoV-2 vaccine will face the same questions on whether Guillain-Barré syndrome is related to the infection itself or to the vaccine. Thus, information on the exact infectious agent is crucial for defining the adverse events of SARS-CoV-2 vaccines. A pathogenic mechanism to link COVID-19 and Guillain-Barré syndrome has not yet been described. However, a molecular mimicry mechanism, autoimmune response against aberrant modification of nervous tissue by infection, and para-infectious immune dysfunction are common explanations for their potential association. We suggest that all these mechanisms should be investigated in COVID-19-related Guillain-Barré syndrome. For example, molecular mimicry with heat shock proteins (HSPs) was reported as a potential pathogenic mechanism of Guillain-Barré syndrome after SARS-CoV-2 infection.5Lucchese G Flöel A SARS-CoV-2 and Guillain-Barré syndrome: molecular mimicry with human heat shock proteins as potential pathogenic mechanism.Cell Stress Chaperones. 2020; 25: 731-735Crossref PubMed Scopus (92) Google Scholar HSPs might also promote a superantigen response, which contributes to the para-infectious response. To establish association and potential causality, researchers should endeavor to collect data from as many cases with COVID-19 as possible from whom SARS-CoV-2 is presumed as the single or joint cause, on the basis of accurate and timely diagnosis of SARS-CoV-2 infection. We declare no competing interests. Provisional case definitions for COVID-19-associated neurological disease – Authors' replyWe read with interest the Correspondence by Hai-Feng Li and colleagues on our proposed definitions for COVID-19-associated neurological disease.1 We thank the authors for recognising the importance of collecting cases together with accurate diagnostic evidence to elucidate disease mechanisms. Full-Text PDF Neurological associations of COVID-19The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. Full-Text PDF