First UK-wide study describes brain complications in some patients with severe COVID-19

Summary: A new study highlights the most common neurological and psychological complications that arise as a result of coronavirus infection. The most common brain complication was stroke, reported in 77 of 125 patients studied. Of those, 57 patients had a stroke caused by a blood clot in the brain. Behavioral changes, confusion, and altered mental state were also reported in a significant number of patients. Depression and anxiety were also commonly reported. Ten patients developed psychosis as a result of COVID-19, and six developed a dementia-like syndrome.

Source: The Lancet

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 and is published today in The Lancet Psychiatry journal.

All of the patients included in the study were selected for inclusion by expert doctors and therefore likely represent the most severe cases. It is not possible to draw conclusions about the total proportion of COVID-19 patients likely to be affected based on this study and in light of these findings further research is now needed, the authors say.

Researchers say their report offers the first detailed snapshot of the breadth of neurological complications in COVID-19 patients and should help to direct future research to establish the mechanisms of such complications so that potential treatments can be developed.

Dr Benedict Michael, lead-author of the study, from The University of Liverpool said: “There have been growing reports of an association between COVID-19 infection and possible neurological or psychiatric complications, but until now these have typically been limited to studies of ten patients or fewer. Ours is the first nation-wide study of neurological complications associated with COVID-19, but it is important to note that it is focused on cases that are severe enough to require hospitalisation.”

To investigate the breadth of COVID-19 complications that affect the brain, researchers set up a secure, UK-wide online network for specialist doctors to report details of specific cases. These portals were hosted by professional bodies representing specialists in neurology, stroke, psychiatry and intensive care. Data was collected between 2 April and 26 April 2020, during the exponential phase of the pandemic.

Professor Sarah Pett co-author of the study, from University College London, UK, said: “This data represents an important snapshot of the brain-related complications of COVID-19 in hospitalised patients. It is critically important that we continue to collect this information to really understand this virus fully. We also need to understand brain-complications in people in the community who have COVID-19 but were not sick enough to be hospitalised. Our study provides the foundations for larger, hospital and community-based studies. These studies will help inform on the frequency of these brain complications, who’s most at risk of getting them, and ultimately how best to treat.”

Some 153 cases were reported during the study period, of which full clinical details were available for 125 patients. The study included patients with confirmed COVID-19 infection by PCR test (114 people), probable infection as diagnosed from chest X-rays or CT scans (6 people), and possible infection, where patients had symptoms consistent with disease but diagnostic tests were either negative or not done (5 people).

The most common brain complication observed was stroke, which was reported in 77 of 125 patients. Of these, 57 patients had a stroke caused by a blood clot in the brain, known as an ischaemic stroke, nine patients had a stroke caused by a brain haemorrhage, and one patient had a stroke caused by inflammation in the blood vessels of the brain. Age data was available for 74 of the patients who experienced a stroke and the majority were over 60 years of age (82%, 61/77).

39 patients showed signs of confusion or changes in behaviour reflecting an altered mental state. Of these, nine patients had unspecified brain dysfunction, known as encephalopathy, and seven patients had inflammation of the brain, medically termed encephalitis. Long-term follow-up studies to assess duration and severity of these complications are needed.

The remaining 23 patients with an altered mental state were diagnosed with psychiatric conditions, of which the vast majority were determined as new diagnoses by the notifying psychiatrist (92%, 21/23). Although most psychiatric diagnoses were determined as new by the notifying psychiatrist or neuropsychiatrist, the researchers say they cannot exclude the possibility that these were undiagnosed before the patient developed COVID-19.

The 23 patients with psychiatric diagnoses included ten patients with a new-onset psychosis and six patients with a dementia-like syndrome. Seven patients had signs of a mood disorder, including depression and anxiety (7/23).

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Researchers say their report offers the first detailed snapshot of the breadth of neurological complications in COVID-19 patients and should help to direct future research to establish the mechanisms of such complications so that potential treatments can be developed. Image is in the public domain.

Age information was available for 37 of the 39 patients with an altered mental state and of those, around half were aged under 60 years of age (49%, 18/37).

The researchers say the high proportion of younger patients diagnosed with psychiatric conditions after showing signs of an altered mental state could be because these patients may be more likely to be referred to a psychiatrist or other specialist doctor, whereas confusion or behaviour changes in older patients may be more likely to be attributed to delirium and not investigated further. Detailed long-term studies are needed in order to confirm if there is any link between COVID-19 infection and the onset of psychiatric or neuropsychiatric complications in younger patients. Such studies should include comparison of the immune response in affected patients and those not affected, as well as investigation of genetic factors that might underpin the development of disease, the researchers say.

Dr Benedict Michael, one of the lead authors of the study, from the University of Liverpool, said: “Our study is an important early step towards defining neurological complications in COVID-19 patients, which will help with health policy planning as well as informing the immediate next steps in COVID-19 neuroscience research. We now need detailed studies to understand the possible biological mechanisms underlying these complications so that we can explore potential treatments.”

About this neuroscience research article

Source:
The Lancet
Media Contacts:
Lancet Press Office – The Lancet
Image Source:
The image is in the public domain.

Original Research: Open access
“Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study”. by Dr Benedict Michael et al.
The Lancet Psychiatry doi:10.1016/S2215-0366(20)30287-X

Abstract

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

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.

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