Covid on the Brain

As we pass 6 months of lockdown measures in the UK, some long term symptoms of covid-19 are starting to emerge. Alongside viral fatigue and continued breathing difficulties, less obvious, neurological, health problems are becoming more of a concern. So what do we know about the effects of coronavirus on the brain to date, and should we be worried about a “silent wave” of neurological problems?

Neurological symptoms started to emerge earlier in the pandemic, but as the number of cases and the death toll continue to rise, there is now enough data to begin analysing these effects and their prevalence. Back in April/May (2020) reports began to state symptoms other than a continuous cough and fever, and the loss of taste and/or smell (anosmia, which can be a symptom of some neurological conditions) was added to the list of covid-19 symptoms to look for. These symptoms, along with headaches and dizziness, are mild neurological problems. Whilst a study in China which looked at hospitalised patients and found ~5% experienced anosmia, a similar, larger study conducted with patients from Belgium, France, Spain and Italy found up to 85% of patients were effected by anosmia. Unfortunately, anosmia is specific to the individual as it can be a reduced ability to smell/taste, rather than a complete lack, so not always easy to quantify.

However, as well as post-viral fatigue, worrying neurological conditions have been documented including strokes, seizures, encephalitis (the potentially fatal inflammation of the brain), and Guillain–Barré syndrome (where peripheral nerves do not function well and can be an ascending paralysis from the feet up), of which cases have risen globally since covid-19 emerged. A potential rise in Parkinson’s disease diagnosis is also of concern. Following the Spanish flu in 1918, the risk of developing Parkinson’s disease increased two to three fold. (Although I will not go into the mechanisms of covid-19 and Parkinson’s here, you can find an article recently published HERE about researchers in Australia investigating the links.) While the majority of neurological symptoms/conditions seen after a covid-19 diagnosis have been documented in individuals who suffered from severe infection, there are cases also in those who only had mild respiratory symptoms, including blood clotting which led to stokes. Neurologists worry such conditions could be a “hidden epidemic” after the pandemic, with the added concern that other viruses can lay dormant in neurons and reactivate to cause disease later (e.g. influenza, measles, and herpes which can lead to meningitis). So what do we know, and how does a virus reach our brain?

There are two main ways in which neurological conditions may arise as a result of a covid-19 infection. Firstly, the direct method: The brain expresses a protein, ACE2, which is involved in blood pressure regulation, and also found on endothelial cells which line blood vessels, the lungs, heart, kidneys and intestines. Numerous lab-based studies have now shown that the covid-19 virus uses the ACE2 protein to enter cells and subsequently infect them. By infecting endothelial cells, the virus can pass from the respiratory tract to the blood and across the blood brain barrier (BBB). Once in the brain, the virus can replicate and potentially cause neurological disorders by directly attacking neurons for example. Secondly, the indirect method: It is possible to develop neurological symptoms/conditions as a result of an over reaction of the immune system, leading to inflammation and organ failure. Conditions such as encephalitis, mentioned above, can occur this way. Lack of oxygen is also known to cause neurological issues. As the surfaces of the small air sacs in the lungs become thicker during infection, oxygen exchange with the blood is harder and can lead to oxygen deprivation of the brain.

Evidence is now however pointing towards covid getting to the brain. While post-mortem studies in the UK found changes to the blood vessels which supply oxygen to the brain, (causing the tissue to die as it hasn’t received enough oxygen) it was not clear if this is a direct effect of the virus or due to lack of oxygen caused by breathing difficulties. The team are now looking for the virus in brain tissue. However, plenty of viruses are known to work their way into the brain and nervous system, including other coronaviruses . SARs (another coronavirus) has been found in brainstems (the part which sits between the spinal cord and the brain, helping to regulate breathing) in previous rat studies. If long term neurological problems are likely, current treatments need to be potentially reconsidered. Antiviral treatments are currently focused on accessing the lungs, but to treat a virus on the brain a completely different set of criteria (such as crossing the BBB, which most drugs struggle to do) need to be considered.

The effects of covid-19 will affect the world for years, if not decades. Be that viral fatigue, economic hardship, lost education, or a wave of indirect symptoms we’re not yet aware of. While it is still not clear if certain individuals are most likely to fall victim to these disorders, most cases have so far occurred in those with severe covid-19 and of those only a very small fraction have been seen to experience damage to the brain/nervous system as a result. Researchers are suggesting long-term screening of those recovering from the virus to monitor for signs of neurological conditions resulting from covid infection, in an attempt to keep on top of the potential “silent wave”.

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