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Neurological associations of COVID-19.
Lancet Neurol. 2020 09; 19(9):767-783.LN

Abstract

BACKGROUND

The 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.

RECENT DEVELOPMENTS

A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2-6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. WHERE NEXT?: Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

Authors+Show Affiliations

National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; The Walton Centre National Health Service (NHS) Foundation Trust, Liverpool, UK.Queen Square Institute of Neurology, University College London, London, UK.National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Tropical and Infectious Diseases Unit, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK; Christian Medical College, Vellore, India.National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; The Walton Centre National Health Service (NHS) Foundation Trust, Liverpool, UK.National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Encephalitis Society, Malton, UK.Alder Hey Children's NHS Foundation Trust, Liverpool, UK.National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Tropical and Infectious Diseases Unit, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; The Walton Centre National Health Service (NHS) Foundation Trust, Liverpool, UK; Tropical and Infectious Diseases Unit, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK. Electronic address: tsolomon@liverpool.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

32622375

Citation

Ellul, Mark A., et al. "Neurological Associations of COVID-19." The Lancet. Neurology, vol. 19, no. 9, 2020, pp. 767-783.
Ellul MA, Benjamin L, Singh B, et al. Neurological associations of COVID-19. Lancet Neurol. 2020;19(9):767-783.
Ellul, M. A., Benjamin, L., Singh, B., Lant, S., Michael, B. D., Easton, A., Kneen, R., Defres, S., Sejvar, J., & Solomon, T. (2020). Neurological associations of COVID-19. The Lancet. Neurology, 19(9), 767-783. https://doi.org/10.1016/S1474-4422(20)30221-0
Ellul MA, et al. Neurological Associations of COVID-19. Lancet Neurol. 2020;19(9):767-783. PubMed PMID: 32622375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurological associations of COVID-19. AU - Ellul,Mark A, AU - Benjamin,Laura, AU - Singh,Bhagteshwar, AU - Lant,Suzannah, AU - Michael,Benedict Daniel, AU - Easton,Ava, AU - Kneen,Rachel, AU - Defres,Sylviane, AU - Sejvar,Jim, AU - Solomon,Tom, Y1 - 2020/07/02/ PY - 2020/04/24/received PY - 2020/05/27/revised PY - 2020/06/04/accepted PY - 2020/7/6/pubmed PY - 2020/9/2/medline PY - 2020/7/6/entrez SP - 767 EP - 783 JF - The Lancet. Neurology JO - Lancet Neurol VL - 19 IS - 9 N2 - BACKGROUND: The 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. RECENT DEVELOPMENTS: A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2-6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. WHERE NEXT?: Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base. SN - 1474-4465 UR - https://www.unboundmedicine.com/medline/citation/32622375/Neurological_associations_of_COVID_19_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(20)30221-0 DB - PRIME DP - Unbound Medicine ER -