Brain complications in patients with COVID-19 — First UK nationwide surveillance study

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Researchers at the University of Liverpool have led the first nationwide surveillance study of the neurological complications of COVID-19. A study of 153 patients treated in UK hospitals during the acute phase of the COVID-19 pandemic describes a range of neurological and psychiatric complications that may be linked to the disease, including stroke and an altered mental state such as brain inflammation, psychosis and dementia-like symptoms.

The findings provide valuable and timely information urgently needed by clinicians, researchers, and funders to inform the next steps in neuroscience COVID-19 research and health policy planning. Increasingly, concerns regarding potential neurological complications of COVID-19 are being reported. However, most published reports have been limited to individual cases or small case series and even larger studies have been limited by both geography and specialty. Consequently, many important questions remain, such as how common complications are, whether novel syndromes are emerging, and which people are most at risk.

To address this, the CoroNerve Studies Group, a collaboration between the universities of Liverpool, Southampton, Newcastle and University College London, developed a rapid notification case identification system across the spectrum of major UK neuroscience professional bodies, representing neurology, stroke, psychiatry, and intensive care. During three weeks of the exponential pandemic phase, the researchers identified 153 cases from across the UK who had both a new COVID-19 diagnosis and a new neurological or psychiatric diagnosis requiring hospital admission, including those admitted to intensive care and/or recovering from critical illness.

The median age of the patients was 71 (23-94) years. Of the 125 patients for whom complete clinical data was available, 57 (44%) suffered ischemic strokes and 39 (31%) experienced an altered mental state reflecting both neurological and psychiatric diagnoses.

Whereas 61 (82%) cases of cerebrovascular events occurred in those over 60 years old, half of cases with an altered mental state were under 60 years old.

Dr Benedict Michael, who led the study for the University of Liverpool said: “Whilst an altered mental state was being reported by some clinicians, we were surprised to identify quite so many cases, particularly in younger patients, and by the breadth of clinical syndromes ranging from brain inflammation (encephalitis) through to psychosis and catatonia.

“Clinicians should be alert to the possibility of patients with COVID-19 developing these complications and, conversely, of the possibility of COVID-19 in patients presenting with acute neurological and psychiatric syndromes.”

It is not possible to draw conclusions about the total proportion of COVID-19 patients likely to be affected based on this study. Larger studies are now needed to identify the broader cohort of COVID-19 patients both in and outside of hospitals, to determine clearer estimates of the prevalence of these complications, those at risk, and impact on recovery.

Co-author Professor Tom Solomon, director of the National Institute for Health Research Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool said: “This study provides a great snapshot of the spectrum of COVID-19 associated neurological disease in the UK. Now we can recognise these problems, we need to understand in more detail why some patients are developing these complications, and what we can do to stop it. It will also be interesting to see how these data compare with other countries.”

The CoroNerve Studies Group is supported by the Association of British Neurologists, Royal College of Psychiatrists, British Association of Stroke Physicians, British Paediatric Neurology Association, NeuroAnaesthesia and Critical Care Society, Intensive Care Society, Faculty of Intensive Care Medicine and the Encephalitis Society.

The researchers are supported by grants from the Medical Research Council, Wellcome, National Institute of Health Research and Academy of Medical Sciences.

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.

Abstract
Aravinthan Varatharaj, Naomi Thomas, Mark A Ellul, Nicholas W S Davies, Thomas A Pollak, Elizabeth L Tenorio, Mustafa SultanAva 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

 

University of Liverpool material

 

The Lancet Psychiatry abstract

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