COVID-19 and the brain; A new wave of neurological disorders

Memory problems, chronic fatigue, psychiatric illness: How COVID-19 can cause extensive damage to the brain

Writer: Clíona Farrell
Editor: Pauline Munchenberg
Artist: Doheon Kim

COVID-19 has paralysed the world for more than a year. Although we know COVID-19 as a respiratory illness, the profound effects it can have on the brain are astonishing. In a recent panel at the virtual Cold Spring Harbour Neurodegenerative Disease Conference, prominent neurologists Dr. Walter Koroshetz and Dr. Anna Nordvig gathered to discuss how COVID-19 can cause extensive damage to the brain. The audience, including myself, was struck by the sheer number of neurological symptoms now known to be directly associated with COVID-19. From chronic fatigue to stoke, psychosis to anaesthesia resistance, the possible consequences seemed endless.

During COVID-19 infection, the most common symptoms that affect the nervous system are muscular pains, headache, fatigue and loss of taste and smell. But patients can also develop strokes, delirium, encephalopathy and brain swelling. Generally speaking, patients with more severe respiratory infection can develop more debilitating neurological symptoms. However, in July 2020, a study from the UCL Queen Square National Hospital for Neurology showed that this is not always the case. In their study, some patients with severe neurological complications, including neuroinflammatory disorders and stroke, had not suffered severe respiratory COVID-19 disease. 

Because people infected with SARS-CoV-2 can lose their sense of taste and smell, it was initially proposed that the nasal passages might offer a route for the virus to attack the brain. Instead, scientists showed that the virus infects not the neurons themselves, but epithelial cells that line the nasal passage. These cells support the olfactory neurons and when they are not functioning properly, our sense of smell and taste can be disrupted.

Not only are people suffering from neurological complications during COVID-19 infection, but post-infectious disorders such as ‘brain fog’ have been widely reported. Today, thousands of COVID-19 survivors are suffering from debilitating neurological conditions months after initially testing positive. Post-COVID brain fog covers a wide range of symptoms and affects people in many different ways, with sufferers describing memory problems, fatigue and even new anxiety and depression after recovering from the initial infection. In a survey characterising long COVID in more than 3,500 international patients over a 7-month period, the most common persisting symptoms were fatigue, cognitive dysfunction and post-exertional malaise, each affecting between 50-80% of the cohort. It is currently unclear how long these effects may last.

But how exactly is SARS-CoV-2 causing neurological complications? In healthy individuals, the brain is protected from the entry of unwanted or toxic materials, including viruses, by the blood brain barrier. Early in the coronavirus outbreak, the question on the mind of neuroscientists and neurologists alike was whether this virus could surpass or penetrate the barrier. By now, multiple autopsy studies have been conducted on the brains of people who have died from COVID-19. Although there is a mixed verdict among doctors, most studies have failed to show many, if any, virus particles inside the brain. When compared to Rabies, a virus that specifically acts to infect the brain of the host, the viral load within the brain of COVID-19 patients is minimal. But of course, we also have to remember that post-mortem studies only show what happens to the sickest patients, and not those who survive the infection. 

If the virus cannot reach our brain, how is it causing such debilitating neurological deficits? The virus enters the body through the nose or mouth. From there, it moves down to the lungs, where it can enter our blood ‒ a path to organs all over the body. On recognising the virus, the immune system reacts by sending a flood of immune cells and inflammatory molecules, called cytokines, to attack the virus. This attack can trigger an inflammatory reaction in the brain, where the resident brain immune cells, called microglia, release more inflammatory cytokines and free radicals. 

Like in the nasal passage, the virus can also attack the epithelial support cells of the blood brain barrier, kicking the inflammatory state of the brain into overdrive. This cycle of inflammation can be further propagated by oxygen deprivation associated with COVID-19, even leading to blood clots and strokes in some patients. What starts out as a protective response to fight the virus can lead to chronic inflammation, harming neuronal cells. Depending on the function of these neurons, cognitive or motor circuits can be affected. This is seen in long COVID sufferers and is likely to contribute to many of the neurological symptoms caused by the disease.

As scary and strange as these neurological disorders may sound, pandemics of the past, including the 1918 flu pandemic, SARS and Ebola, have all been linked to nervous system complications, from neuropsychiatric disorders to Parkinsonism. After the original SARS outbreak, a follow up study in Hong Kong showed 40% of infected patients suffered from a new psychiatric illness and/ or chronic fatigue months after recovering from their respiratory infection, likely caused by a similar neuroinflammatory reaction as in COVID-19. These disorders prevent people from returning to their lifestyle prior to infection; some people can no longer work and others suffer from strained personal relationships. It is still early days for long-term COVID-19 research but these insights from previous pandemics shine a light on the possible health consequences for sufferers of COVID-19 that may last a great deal longer than the infection itself.

Neurological effects of COVID-19 can be temporary or more long-term, particularly in those who suffer from severe infection. However, it’s not just the elderly who are at risk. People in their twenties, thirties and forties who have never had psychological problems or sleep disturbance before are also presenting with these symptoms. The good news is that clearer research on these questions is emerging each day. With the number of vaccines being produced and administered increasing, the prospect of stopping the spread of COVID-19 and its associated neurological deficits is within reach. Here in the UK, as we follow the roadmap into a post-COVID world, hopefully understanding these risks makes it that small bit easier to stay sensible until it is safe to emerge in summer 2021.

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