Evidence
Alert

Brain and nerve complications are more common than expected in younger patients with severe COVID-19

People aged under 60 who are hospitalised with COVID-19 are more likely than expected to experience severe psychiatric symptoms. Research found that altered mental states such as psychosis are being reported in these younger patients.  It confirmed that strokes and other neurological symptoms are common in severe COVID-19.

An initial study included 153 cases reported by stroke physicians, neurologists and psychiatrists in the UK in April 2020.  It found that most strokes occurred in people aged over 60. But about half the cases of altered mental state such as psychosis or swelling of the brain (encephalitis) were in younger people.

These complications may reflect damage to the brain and nervous system caused by the coronavirus. In the study, 'altered mental state' included any sudden change in personality, behaviour, thinking abilities, or consciousness. Neurological symptoms included any symptoms involving the nerves or muscles. Strokes included blood clots or bleeds in the brain.

Further research may help researchers work out how the virus causes these complications. This in turn may help them develop appropriate treatment pathways.

What’s the issue?

Psychiatric and neurological symptoms were reported after previous outbreaks of viral illness, including H1N1 swine flu, although they were not common.

Early reports of neurological symptoms associated with COVID-19 came from China and Italy. They led UK neurologists to think that the symptoms could be more common than expected with COVID-19. Alternatively, there could be so many cases of COVID-19 that even rare complications were being seen often. Doctors were reporting symptoms caused by brain inflammation, similar to that in previous infectious diseases, but also strokes and new psychiatric disorders.

The clinical scientists involved in this research wanted to reach beyond neurologists and study a wider group of patients. They set up online portals via professional bodies, to allow doctors to register brief details of UK patients showing these symptoms. This paper reports on the analysis of the first 153 cases reported to portals by April, 2020.

What’s new?

Complete data was available for 125 patients with confirmed or probable COVID-19 infection and psychiatric or neurological symptoms. The numbers of reports rose in line with the rise in COVID-19 cases overall. This suggests that these complications arose at the time of the infection, rather than weeks or months later.

Of the 125 cases:

  • 77 (62%) had a stroke (three quarters of whom had ischaemic stroke caused by blood clotting, which may be a feature of COVID-19)
  • 39 (31%) had an altered mental state
  • 6 (5%) had symptoms affecting the peripheral nerves such as numbness, weakness and pain, and three had other neurological symptoms

More than half (23 of 39) patients with altered mental state were diagnosed with a psychiatric disorder such as psychosis, a dementia-like condition, catatonia (unresponsiveness), anxiety or depression. Of the others, 16 had been diagnosed with damage or inflammation to the brain.

Half of the patients with altered mental state were younger than 60. Most of those who had a stroke (82%) were older than 60.

The reports were made via online portals set up by the Association of British Neurologists, British Association of Stroke Physicians and Royal College of Psychiatrists and others. Only brief information was requested so that doctors had time to report while the pandemic was in its early stages.

Cases were identified as confirmed COVID-19 if the patient had tested positive (92%), probable if they had chest scan or x-ray suggesting the disease but no positive test result (4%), and possible if the disease was suspected by the doctor but there was no positive test (4%).

Why is this important?

This first study is small, but it shows that younger people (under 60) may be as likely as older people to show symptoms such as psychosis after infection. This is important as younger people have been thought less likely to have serious complications from COVID-19. It confirms previous reports that strokes are relatively common after COVID-19, especially in older people. It suggests that COVID-19 may be linked to brain inflammation or damage.

If the patients in this study can be fully investigated, scientists may discover more about the causes of these neurological complications. For example, they could be caused by immune response, the virus entering the brain, inflammation in the blood vessels of the brain, or multi-infarcts in the brain (when blood clots stop the blood supply).

Better understanding of the causes could enable doctors to recommend appropriate treatments. Some people may benefit from anticoagulant drugs to prevent blood clots; others may benefit from steroids to reduce inflammation.

What’s next?

The authors are gathering and analysing more detailed clinical information about the patients reported in this study, and others reported since (540 are now included). They are seeking funding for a further study to include more clinical investigations such as analysis of spinal fluid, blood and brain imaging.

Author Benedict Michael is co-chairing a World Health Organisation commissioned task force which will consider how to use the information from the ongoing research project in guidance for clinicians.

The task force will consider whether people with new-onset altered mental state or another acute neurological problem should be tested for COVID-19. Some patients with few respiratory signs present with this symptom.

They will consider which tests and investigations people with COVID-19 and neurological symptoms should undergo. Doctors need to be sure COVID-19 is the cause of the symptoms, and to know how patients should be managed.

You may be interested to read

The full paper: Michael B, and others. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. The Lancet Psychiatry 2020;7:875-882

A blog from the study authors collating new research on this topic: The Neurology and Neuropsychiatry of COVID-19 

Funding

This research was supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, and the NIHR Global Health Research Group on Brain Infections.

Commentaries

Study author

The number of patients with these complications – 125 in three weeks – was a surprise. We saw 23 in two years in the H1N1 swine flu pandemic.

Stroke is well recognised as a complication of COVID-19. It was interesting that the second most common complication was alteration in mental state.  Patients who look similar when they present with confusion, changes in personality, maybe psychosis have different underlying causes. Some had encephalitis with inflammation in their spinal fluid, some had encephalopathy but no evidence of inflammation, and others had a primary psychiatric diagnosis.

A large chunk of those with altered mental states were younger. A quarter were in their 20s, 30s and 40s. We typically think of these groups as not really needing to worry about COVID.

Questions about how a pandemic virus causes neurological complications have been around since the Spanish flu in 1918. This paper shows the volume and the breadth of potential neurological complications.

For the first time we have established a cohort of 540 people in whom we can actually answer those questions. It’s a once in mankind opportunity. We did not have genetic sequencing and brain imaging in 1918. We can answer the questions the neuroscience community has been grappling with for 100 years with this group of patients.

We are seeing patients who are relatively young and otherwise well, with normal oxygen levels, no electrolyte disturbance, not taking drugs that could cause confusion. We need to understand why these people – with no existing risk factors – are having strokes and encephalopathy.

Benedict Michael, Senior Clinician Scientist Fellow, Institute of Infection and Global Health, University of Liverpool and Honorary Consultant Neurologist at The Walton Centre NHS Foundation Trust

Member of the public 

People need to be followed up over time to see if altered mental states remain and for how long. The effects on younger patients were particularly note-worthy and warrant further investigation.

The key organisations mentioned in the paper make up the spectrum of major UK neuroscience bodies. They will need to filter this information to GPs and NHS Trusts to effect further data collection and evidence. Perhaps recommendations can then be made with real conviction.

Shannon Sheppard, Public Contributor, Essex

Conflicts of Interest

Several study authors report receiving fees and research funding from various pharmaceutical companies.