COVID-19: It's more than just a respiratory illness.

  • Hi, I’m Alice, a third year undergraduate Biology student at Durham university. Over the Summer, I have been working with one of my professors to investigate what is known about the effects of COVID-19 on the brain and thought I would share my findings as this is something everyone should be aware of!

     

    Fever, cough, and shortness of breath were initially the hallmark symptoms of COVID-19, but with more research it is becoming increasingly clear that this virus effects the central and peripheral nervous systems more commonly than previously thought. 

    This finding must change the way COVID-19 patients are screened, monitored, and treated to ensure neurological deficits don’t go unnoticed, thus avoiding potential long-term damage.

    Three-stage classification of the effect of SARS-CoV-2 on the brain

    A new review outlines a three-stage classification of the impact of COVID-19 on the central nervous system. This classification system mainly focuses on the ‘cytokine-storm’; a surge of inflammatory cytokines caused by SARS-CoV-2. This involves an increase in IL-1, IL-6, and TNF, which increases vascular permeability, edema, widespread inflammation and hypercoagulation cascades. 

    Stage 1

    In the first stage, the cytokine storm is low and SARS-CoV-2 binding to ACE2 receptors is limited to the nasal and gustatory epithelial cells. It is in this stage that people experience anosmia (loss of smell) and gustatory impairments.

    Anosmia is the most common neurological presentation of COVID-19 and is often the only presenting symptom, frequently presented in patients in their early 20s. 

    A theory of neuronal retrograde dissemination suggests SARS-CoV-2 can bind to ACE2 receptors on cells of the olfactory epithelium and transport along olfactory sensory neurons to the olfactory bulb, where it can spread to the rest of the brain. It is the blocking of the ACE2 receptors that causes anosmia.

    Stage 2

    At stage 2, there is a robust immune response that leads to inflammation in blood vessels, increased hypercoagulability factors and the formation of blood clots in cerebral veins and arteries, thus leading to strokes.

    Most of the strokes in COVID-19 patients are due to ischemic events (clots), as a result of increased hypercoagulability factors. For example, a patient with COVID-19 had suffered from two serious strokes and it was found that he had high levels of D-dimer, a marker for blood clotting. Normally, these levels are below 300 and in stroke patients can rise to 1000, but in this patient’s case they were over 80,000. There have also been cases of intracranial haemorrhage reported, thought to be due to the higher levels of ANGII, which are associated with vasoconstriction and peripheral vascular resistance.

    Stage 3

    In stage 3, an explosive inflammatory response is caused by a severe cytokine storm, leading to the breaching of the blood brain barrier and the entry of cytokines, blood components and viral particles. This causes neuronal cell death and encephalitis, characterised by seizures, delirium, coma, loss of consciousness or death.

    Patients in stage 3 are more likely to have long term consequences, as the virus has penetrated the brain and can remain dormant in neurons for many years. Despite not being acutely toxic, they lead to abnormal misfolding and aggregation of proteins and therefore studies of coronaviruses have shown a correlation between infections and risk of MS or Parkinson’s later in life. It is also thought that this inflammatory response in the brain may trigger or accelerate the mechanisms that underlie the early stages of neurodegenerative disorders.

    Looking forward

    I am sure you’ll agree that it is clear COVID-19 has widespread effects on the brain, and we would be naive to think we know the extent of these. Therefore, there are still many questions that need answering. Arguably, the most important question that remains unanswered is how will the brains of COVID-19 patients be affected in years to come?

     

    Picture from: https://www.medscape.com/viewarticle/931658