Neurological Associations of COVID-19

The Lancet Neurology, Forthcoming

53 Pages Posted: 7 May 2020 Last revised: 5 Jun 2020

See all articles by Mark Ellul

Mark Ellul

University of Liverpool - Institute of Infection and Global Health

Laura Benjamin

University College London - Institute of Neurology

Bhagteshwar Singh

University of Liverpool - Institute of Infection and Global Health

Suzannah Lant

University of Liverpool - Institute of Infection and Global Health

Benedict Michael

University of Liverpool - Institute of Infection and Global Health

Ava Easton

Encephalitis Society

Rachel Kneen

Alder Hey Children's Hospital

Sylviane Defres

Tropical and Infectious Diseases Unit, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK

James Sejvar

Government of the United States of America - Division of High-Consequence Pathogens and Pathology

Tom Solomon

University of Liverpool - Institute of Infection and Global Health

Date Written: April 24, 2020

Abstract

Background: The COVID-19 pandemic, caused by 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. Based on knowledge of other coronaviruses, especially those that caused the SARS and MERS epidemics, we might expect to see rare cases of central nervous system (CNS) and peripheral nervous system (PNS) disease caused by SARS-CoV-2.

Recent developments: A growing number of case reports and series describe a wide array of neurological manifestations, but many lack detail, reflecting the challenge of studying such patients. Encephalopathy is relatively common, being reported for 93 patients in total, including 16 (7.5%) of 214 hospitalised COVID-19 patients in Wuhan, China, and 40 (69%) of 58 in intensive care with COVID-19 in France. Encephalitis has been described in 8 patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 is detected in the cerebrospinal fluid of some patients. Anosmia and ageusia are common and may 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 1.6-6% of hospitalised COVID-19 cases. So far, 88 patients have been described, mostly with ischaemic stroke, who frequently have vascular events in the context of a pro-inflammatory hypercoagulable state with elevated CRP, 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, such as hypoxic encephalopathy and critical care neuropathy, from those caused directly or indirectly by the virus; these include infectious, para- and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognising SARS-CoV-2 neurological disease in patients whose respiratory infection is mild or asymptomatic may prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will remain small. However, these patients may be left with severe neurological sequelae. With so much of the population infected, the overall number of neurological patients, and their associated health, social and economic costs, may be large. Healthcare planners and policymakers must prepare for this eventuality. The many ongoing studies investigating the neurological association will increase our knowledge base.

Note: Funding: The research was funded by the NIHR Global Health Research Group on Brain Infections (No. 17/63/110) and the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant No. NIHR200907). MAE, SL and TS are supported by the European Union's Horizon 2020 research and innovation program ZikaPLAN (Preparedness Latin America Network; grant agreement No. 734584). MAE is also supported by the Association of British Neurologists though a Clinical Research Training Fellowship. BDM has received funding from the Medical Research Council, Wellcome Trust and Academy of Medical Sciences.

Conflict of Interest: TS was an adviser to the GlaxoSmithKline Ebola Vaccine programme and chaired a Siemens Diagnostics clinical advisory board. All other authors report no competing interests.

Keywords: COVID-19, coronavirus, SARS-CoV-2, neurology, encephalitis, encephalopathy, myelitis, myelopathy, Guillain-Barré Syndrome, cerebrovascular disease, stroke, vasculitis, nervous system, virus

Suggested Citation

Ellul, Mark and Benjamin, Laura and Singh, Bhagteshwar and Lant, Suzannah and Michael, Benedict and Easton, Ava and Kneen, Rachel and Defres, Sylviane and Sejvar, James and Solomon, Tom, Neurological Associations of COVID-19 (April 24, 2020). The Lancet Neurology, Forthcoming , Available at SSRN: https://ssrn.com/abstract=3589350 or http://dx.doi.org/10.2139/ssrn.3589350

Mark Ellul

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Laura Benjamin

University College London - Institute of Neurology ( email )

Queen Square
London WC1N 3BG
United Kingdom

Bhagteshwar Singh

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Suzannah Lant

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Benedict Michael

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

Ava Easton

Encephalitis Society ( email )

Rachel Kneen

Alder Hey Children's Hospital ( email )

Sylviane Defres

Tropical and Infectious Diseases Unit, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK ( email )

James Sejvar

Government of the United States of America - Division of High-Consequence Pathogens and Pathology ( email )

Atlanta, GA
United States

Tom Solomon (Contact Author)

University of Liverpool - Institute of Infection and Global Health ( email )

8 West Derby Street
Liverpool, L69 7BE
United Kingdom

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