Covid-19 and the brain. What’s going on?

Loss of taste and smell, confusion, brain damage … why are neurological symptoms appearing in people with Covid-19?

As a Neuroscience researcher at Oxford Brain Diagnostics — and having studied Neuroscience at Oxford University for my undergraduate degree — I have been interested in the emerging stories of Covid-19 patients who present with symptoms linked to the brain. These neurological symptoms include (as has been widely shared online) loss of taste and smell. But they can go much further, including confusion and, on very rare occasions, more severe symptoms such as stroke, epilepsy and brain damage. While these are uncommon there has been enough prevalence of these symptoms that a specific Neuro-Covid-19 ward has been set up in Northern Italy, with doctors there warning others around the world to look out for neurological symptoms in Covid-19 patients.

So, I’ve read up on the topic of what’s currently available and here are my thoughts. It’s worth mentioning: there is limited evidence currently available. We must always (and especially now) hold the scientific process in the highest regard: hypothesize, find evidence, test, make conclusions and change these conclusions if new evidence suggests otherwise. I’m also a scientist, not a doctor — see the NHS and Public Health England websites for the latest medical advice.

So, with those reservations in mind, I invite you to explore some of the ideas with me below.

Covid-19 and the Brain: What are the neurological symptoms? And what are the emerging theories that might explain them?

The two most common neurological symptoms that appear in Covid-19 include confusion (~20%) and loss of taste and smell.

In a very small number of patients, neurological symptoms have been reported as severe, including stroke, epilepsy and ‘Acute Hemorrhagic Necrotizing Encephalopathy’. Translated from medical jargon to English, this means: quick, blood vessel-bursting, brain damage causing cell death. There is also a suggestion that a neurological mechanism may be directly involved in the Covid-19 lung and heart failure.

But Covid-19 is a respiratory disease … what has that got to do with the brain?

Let’s have a closer look at these reported neurological symptoms.

Temporary Loss of Taste and Smell

Covid-19 is an infection of the respiratory system. As such, in infected people the virus often lives in the nose, throat and sometimes the lungs. But, in some cases it may go beyond this. It is theorised that the virus can enter the neurons linked to the nose via the nasal tract, because of a receptor on the surface of these cells called ACE2, which is the same type of receptor that the virus uses to get into lung cells.

If this is true, then the virus may block the function of the olfactory (smelling) cells, thereby stopping the olfactory neurons from sending signals to the brain, resulting in loss of smell. It would make sense that this same mechanism explains the accompanying loss of taste, because lots of your taste perception comes from the receptors in your nose … try tasting something while holding your nose and notice the effect! Thankfully these symptoms don’t appear to be permanent — smell and taste go back to normal once the virus is cleared from the body.

Confusion

Evidence is emerging of a relatively high proportion (~20%) of patients presenting with symptoms of ‘confusion’. This means, for example, that the person may be slow or unable to think or speak properly, is disoriented, or struggles to pay attention.

Perhaps the most plausible (and simple) explanation for this is that lower levels of oxygen in the blood (due to reduced lung function) lead to reduced organ function across the body, including brain function. As you might expect, reduced general brain function can result in confusion.

A different, emerging idea is that the virus, in some cases, could get into the central nervous system (CNS), which includes the brain, and from here attack cells directly. If this virus (SARS-CoV-2) acts in a similar way to another virus of the same family (SARS-CoV), it could travel from the lungs to the parts of the brain that control lung and heart function and damage those cells directly. This idea is being investigated further.

Dementia —is there a role?

Another factor — and one that we’re particularly interested in here at Oxford Brain Diagnostics — could be that some patients already have underlying brain deterioration (e.g. due to early stages of dementia) which Covid-19 is exposing.

In the first stages of dementia, the brain starts to deteriorate but symptoms often do not show. The body and brain are relatively good at adapting and coping with the slow ‘background’ neurodegeneration and therefore no obvious signs of cognitive decline show up. But, the theory goes, the body only has finite resources and when the virus attacks, much of the body’s energy is diverted to fighting the virus. This extra energy is no longer available to support the ‘cognitive reserve’ that has enabled the brain to cope with the slowly progressing dementia, and so the cognitive symptoms of the dementia start to appear.

This theory may also apply to non Covid-19 patients too. Doctors around the world will be familiar with the frequent story of a patient who acquires an infection while recovering after surgery and spirals into a state of confusion. In patients with early neurodegeneration, cognitive reserve may be exhausted and signs of dementia begin to appear. At Oxford Brain Diagnostics, we are developing an earlier diagnostic tool for Alzheimer’s Disease, which could help to detect which patients are at risk of this, by picking up earlier signs of the underlying neurodegeneration. More information here.

Severe Neurological Symptoms

A few anecdotal stories and a study from Wuhan are appearing of Covid-19 patients who experience epilepsy, stroke, ataxia (loss of coordination) or a type of brain damage, called ‘encephalopathy’. What could explain this?

From olfactory neurons or the lung cells, the theory goes that the virus can travel up neurons, across synapses, and into the central nervous system, including the brain. A combination of the virus’ direct attack on the brain’s cells and the body’s own resulting immune response causing inflammation could be what’s leading to the severe damage. It’s also possible that this severe immune injury of the brain is happening without the virus entering the nervous system at all, as a result of the immune system going into overdrive in a process called a ‘cytokine storm’. Cytokines are proteins that are a key part of the immune response throughout the body.

A, Brain CT image 1 day after ischemic stroke. White arrowhead indicates the ischemic lesion. B, Chest CT image 1 day after ischemic stroke. Mao et al 2020

Thinking ahead

As you would expect this throws up lots of questions and groups such as Neurocritical Care, who are collecting stories of neurological symptoms in Covid-19 patients, are well placed to begin to explore them.

• What’s the best way to treat Covid-19 patients who present with neurological symptoms?
• Should there be treatments focusing on these neurological symptoms?
• Will there be longer lasting effects of Covid-19, such as chronic tiredness, in patients who suffer the more severe neurological symptoms?

As we collectively respond to this crisis I hope we all will come to think a little more like scientists; to be okay with making decisions in positions of uncertainty by using the best available evidence, accepting that we don’t have all the answers yet, but will work together to gather more evidence and find the right answers soon.

(Please note: None of the information in this article is confirmed — each theory, anecdote and piece of evidence is part of a picture which bit-by-bit the global science community is uncovering and piecing together to understand more).