Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Aravinthan Varatharaj, Naomi Thomas, Mark A Ellul, Nicholas W S Davies, Thomas A Pollak, Elizabeth L Tenorio, Mustafa Sultan, Ava Easton, Gerome Breen, Michael Zandi, Jonathan P Coles, Hadi Manji, Rustam Al-Shahi Salman, David K Menon, Timothy R Nicholson, Laura A Benjamin, Alan Carson, Craig Smith, Martin R Turner, Tom Solomon, Rachel Kneen, Sarah L Pett, Ian Galea, Rhys H Thomas, Benedict D Michael, CoroNerve Study Group, Claire Allen, Neil Archibald, James Arkell, Peter Arthur-Farraj, Mark Baker, Harriet Ball, Verity Bradley-Barker, Zoe Brown, Stefania Bruno, Lois Carey, Christopher Carswell, Annie Chakrabarti, James Choulerton, Mazen Daher, Ruth Davies, Rafael Di Marco Barros, Sofia Dima, Rachel Dunley, Dipankar Dutta, Richard Ellis, Alex Everitt, Joseph Fady, Patricia Fearon, Leonora Fisniku, Ivie Gbinigie, Alan Gemski, Emma Gillies, Effrossyni Gkrania-Klotsas, Julie Grigg, Hisham Hamdalla, Jack Hubbett, Neil Hunter, Anne-Catherine Huys, Ihmoda Ihmoda, Sissi Ispoglou, Ashwani Jha, Ramzi Joussi, Dheeraj Kalladka, Hind Khalifeh, Sander Kooij, Guru Kumar, Sandar Kyaw, Lucia Li, Edward Littleton, Malcolm Macleod, Mary Joan Macleod, Barbara Madigan, Vikram Mahadasa, Manonmani Manoharan, Richard Marigold, Isaac Marks, Paul Matthews, Michael Mccormick, Caroline Mcinnes, Antonio Metastasio, Philip Milburn-McNulty, Clinton Mitchell, Duncan Mitchell, Clare Morgans, Huw Morris, Jasper Morrow, Ahmed Mubarak Mohamed, Paula Mulvenna, Louis Murphy, Robert Namushi, Edward Newman, Wendy Phillips, Ashwin Pinto, David Ashley Price, Harald Proschel, Terry Quinn, Deborah Ramsey, Christine Roffe, Amy Ross Russell, Neshika Samarasekera, Stephen Sawcer, Walee Sayed, Lakshmanan Sekaran, Jordi Serra-Mestres, Victoria Snowdon, Gayle Strike, James Sun, Christina Tang, Mark Vrana, Ryckie Wade, Chris Wharton, Lou Wiblin, Iryna Boubriak, Katie Herman, Gordon Plant, Aravinthan Varatharaj, Naomi Thomas, Mark A Ellul, Nicholas W S Davies, Thomas A Pollak, Elizabeth L Tenorio, Mustafa Sultan, Ava Easton, Gerome Breen, Michael Zandi, Jonathan P Coles, Hadi Manji, Rustam Al-Shahi Salman, David K Menon, Timothy R Nicholson, Laura A Benjamin, Alan Carson, Craig Smith, Martin R Turner, Tom Solomon, Rachel Kneen, Sarah L Pett, Ian Galea, Rhys H Thomas, Benedict D Michael, CoroNerve Study Group, Claire Allen, Neil Archibald, James Arkell, Peter Arthur-Farraj, Mark Baker, Harriet Ball, Verity Bradley-Barker, Zoe Brown, Stefania Bruno, Lois Carey, Christopher Carswell, Annie Chakrabarti, James Choulerton, Mazen Daher, Ruth Davies, Rafael Di Marco Barros, Sofia Dima, Rachel Dunley, Dipankar Dutta, Richard Ellis, Alex Everitt, Joseph Fady, Patricia Fearon, Leonora Fisniku, Ivie Gbinigie, Alan Gemski, Emma Gillies, Effrossyni Gkrania-Klotsas, Julie Grigg, Hisham Hamdalla, Jack Hubbett, Neil Hunter, Anne-Catherine Huys, Ihmoda Ihmoda, Sissi Ispoglou, Ashwani Jha, Ramzi Joussi, Dheeraj Kalladka, Hind Khalifeh, Sander Kooij, Guru Kumar, Sandar Kyaw, Lucia Li, Edward Littleton, Malcolm Macleod, Mary Joan Macleod, Barbara Madigan, Vikram Mahadasa, Manonmani Manoharan, Richard Marigold, Isaac Marks, Paul Matthews, Michael Mccormick, Caroline Mcinnes, Antonio Metastasio, Philip Milburn-McNulty, Clinton Mitchell, Duncan Mitchell, Clare Morgans, Huw Morris, Jasper Morrow, Ahmed Mubarak Mohamed, Paula Mulvenna, Louis Murphy, Robert Namushi, Edward Newman, Wendy Phillips, Ashwin Pinto, David Ashley Price, Harald Proschel, Terry Quinn, Deborah Ramsey, Christine Roffe, Amy Ross Russell, Neshika Samarasekera, Stephen Sawcer, Walee Sayed, Lakshmanan Sekaran, Jordi Serra-Mestres, Victoria Snowdon, Gayle Strike, James Sun, Christina Tang, Mark Vrana, Ryckie Wade, Chris Wharton, Lou Wiblin, Iryna Boubriak, Katie Herman, Gordon Plant

Abstract

Background: Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.

Methods: During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.

Findings: The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23-94; IQR 58-79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.

Interpretation: To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.

Funding: None.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Temporal distribution of the date of admission or first assessment for cases notified to the CoroNerve Study Group and those identified by UK Government public health bodies
Figure 2
Figure 2
Age distribution of all cases notified to the CoroNerve Study Group and national data collected by UK Government public health bodies within the first 3 weeks of CoroNerve accepting notifications
Figure 3
Figure 3
Number of broad and specific clinical case definitions notified in the dataset, including evidence for severe acute respiratory syndrome coronavirus 2 within each grouping, according to the clinical case definition *One patient with opsoclonus-myoclonus syndrome, one patient with sixth nerve palsy, and one patient with seizures. †Two patients with cerebral venous thrombosis, two patients with transient ischaemic attack, one patient with subarachnoid haemorrhage, and five unspecified. ‡1 case with missing SARS-CoV2 data. §One patient with brachial neuritis and one patient with myasthenic crisis. ¶Three patients with depression, two patients with personality change, one patient with catatonia, and one patient with mania.
Figure 4
Figure 4
Age distribution of patients identified through the CoroNerve surveillance study meeting the clinical case definitions for cerebrovascular and neuropsychiatric events

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Source: PubMed

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