Cause for concern: COVID-19’s troubling impact on the brain

We know very little about COVID-19 and the brain, but the knowns are clearly cause for concern, writes Tomás Ryan, associate professor in the School of Biochemistry and Immunology, in an opinion piece that originally appeared in the Sunday Business Post on 19th July 2020
One of the most interesting, and worrying, aspects of COVID-19 is its effect on the brain.We are learning more about this disease every day, and it is now clear that it’s a complex multi-organ disorder, affecting the lungs, heart, kidneys, brain, joints, blood vessels and nervous system. The long-lasting morbidity caused by COVID-19 symptoms of various severity is still unclear.

Over 50 per cent of people infected are asymptomatic, and the infection/mortality rate – including symptomatic and asymptomatic cases – roughly holds at about 1 per cent internationally. It is, however, much more difficult to put a number on the morbidity consequences of the disease.

We primarily think of COVID-19 as a respiratory disorder. In the more severe cases, acute respiratory distress (ARD) syndrome occurs, requiring intensive care. But the effects on lungs can last longer.

On CT scans, 80 to 95 per cent of COVID-19 patients show visible lung damage. Patients frequently show grey patches, called “ground-glass opacities”, which indicate pneumonia.

These opacities peak with symptoms, but also persist at a residual level in the majority of patients at time of discharge. More worryingly, other studies using CT scans report that up to 95 per cent of asymptomatic COVID-19 infections show these lesions in both lungs.

The prevalence of lung effects has led to the possible use of CT scans as a screening tool for travellers, complementing virus tests. At this stage, we do not know the long-term implications and lung scarring of COVID-19 infection.

Heart problems are another significant feature of the disease, with up to 12 per cent of patients showing cardiac damage. COVID-19 is also a disorder of blood clotting, and this can lead to lead to various clinical outcomes. Some people experience pulmonary embolisms while others develop deep vein thrombosis, sometimes requiring the amputation of limbs. For similar reasons, 5 per cent of hospitalised COVID-19 patients have been reported to suffer stroke, which is clearly detrimental to brain health.

But the consequences of COVID-19 for the brain are much broader than the risk of stroke. One study of 214 hospitalised cases in China found neurological symptoms in 36 per cent of patients, and observed that such symptoms were increasingly common in patients with severe infections. Another study in Spain found that 57 per cent of 841 hospitalised patients developed neurological symptoms. In a French study, 70 per cent of 58 COVID-19 patients in ICU showed the same.

Milder neurological symptoms identified in hospitalised patients with COVID-19 include headache, dizziness, muscle aches, anorexia, anosmia or lack of smell and ageusia or distorted taste.

It is not yet clear how prevalent these symptoms are in non-hospitalised patients. More severe neurological symptoms include stroke, impaired consciousness, seizures, Guillain-Barré syndrome (a rare autoimmune disorder), ataxia and movement disorders, visual impairments, and encephalitis.

Researchers at University College London led a pioneering and detailed neurological study of 43 COVID-19 ICU referrals across a range of ages. They identified a recurring set of neurological conditions including encephalopathy with delirium; inflammatory nervous system syndromes, acute demyelinating encephalomyelitis (a life-threatening disease similar in symptoms to multiple sclerosis), Guillain-Barré Syndrome, and other neurological conditions. Long-term studies of such patients are eagerly awaited.

Psychiatric and psychological disorders are also a central consideration. Delirium is found in 80 per cent of cases of acute respiratory distress syndrome. Even before COVID-19 it was known that a quarter of people who experience acute respiratory distress syndrome due to other infections suffer post-traumatic stress disorder (PTSD), while greater numbers experience general anxiety or depression.

There’s no reason to think the same effects won’t hold true for COVID-19 ICU survivors. It is also clear that COVID-19 can cause psychiatric symptoms to appear for the first time in some individuals. A UK-wide surveillance study in Lancet Psychiatry found new onset brain complications in 125 hospital patients with severe COVID-19.

Half had suffered strokes and tended to be older, while others experienced neuropsychiatric symptoms and tended to be younger.

COVID-19 has not been around for long, so we can’t yet estimate its true long-term neurological and psychiatric burden, but evolution does not tend to reinvent the wheel, and we are not completely naïve.

Just as the value of face-coverings was always likely based on the precedents of other coronaviruses such as severe acute respiratory syndrome (Sars) and middle east respiratory syndrome (Mers), we know that post-ICU survivors of acute respiratory distress syndrome are vulnerable to long-term brain morbidity.

In general, research has shown that 20 per cent of acute respiratory distress syndrome survivors experience long-term cognitive impairments lasting years such as memory problems and impaired executive function. Over 60 per cent of Sars survivors showed pathological levels of psychological stress one year after infection. More broadly, following the 1918 Spanish flu pandemic, a great deal of brain disease emerged over the following 10 to 20 years, including waves of encephalitis lethargica (sleeping sickness) suggested to be caused by the pandemic.

We know very little about COVID-19 and the brain, but the knowns are clearly cause for concern. There is far more we do not know, limiting our ability to make prognoses or to treat symptoms. It’s not yet clear which brain effects are due to systemic loss of oxygen (hypoxia), over-activation of the immune system (neuroinflammation), or directly due to the virus. We don’t know how long these neurological disorders may last, and what their prevalence might be in asymptomatic infections.

On the positive side, there have never been so many active scientists as today. Across the world, neuroscientists, neurologists, psychologists, and psychiatrists are stepping outside of their usual lanes to dive into Covid-19 research. One ambitious consortium led by Adrian Owen working at Western University and the University of Toronto in Canada has launched a large online research programme (covidbrainstudy.com) to explore the long-term effects of Covid-19 on cognitive function such as memory and attention in 50,000 people. This study is recruiting volunteer Covid-19 patients from around the world, but I hope this is one scientific endeavour where Ireland does not punch above its weight.

It is noteworthy that Ireland has one neurologist for 45,000 patients, which means we rank dead last out of 45 European countries for the number of neurologists per patient according to the European Academy of Neurology. On average in Europe there are 10,000 patients per neurologist, with well under 5,000 in Austria, Germany, and Italy.

Our mental health services are also stretched beyond capacity, and that was all before the pandemic.

Tomás Ryan is associate professor in the School of Biochemistry and Immunology and principal investigator in the Trinity College Institute of Neuroscience at Trinity College Dublin

 

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