Proposed Mechanism and Routes of Action Of COVID-19
Induced Neurological Dysfunction
COVID-19, arguably one of the greatest public health crises of the generation, is misinterpreted commonly and thought by many to only affect our respiratory (breathing) system due to the overwhelming damage it is capable of causing to our lungs. Yet, this is only half of the story. Prevailing research suggests that there are broad multi-system effects from COVID-19, not least of which include your nervous system; your brain. With a quick glance at the COVID-19 information provided by the World Health Organization, among the list of symptoms is: confusion, anxiety, loss of taste and smell, and at the far reaches of severity, are strokes, brain inflammation and delirium (an extreme form of confusion) (2021). All of these point to some form of attack on the nervous system. Recent research conducted by a team from Cambridge’s department of medicine using diffusion tensor imaging (DTI), a way of tracking brain activity by following water molecules, and magnetic resonance imaging (MRI) reports a possible explanation for these issues (Newcombe, et al., 2021).
The research team examined MRI and DTI scans from six patients with severe COVID-19 related respiratory failure. Of the six patients, four remained unresponsive after being taken off sedatives, one presented with severe delirium, and the last with what is called “generalized myoclonus”, a condition resulting in uncontrolled random jerky movements of the body (Newcombe, et al., 2021). The MRI alone showed no abnormalities or injuries which were capable of explaining the neurological conditions of the patients, but the DTI was very different. From the DTIs, all six patients showed widespread abnormalities when compared to healthy individuals. All four main lobes of the brain: the frontal, temporal, parietal, and occipital cortices as well as the patients’ hippocampi (a portion of the brain important for memory and spatial awareness) showed increased mean diffusivity (MD) (Newcombe, et al., 2021). This means that these locations in the brain showed non-random increases in movement of water molecules towards them, a classic sign of issues in the white matter (inside portions) of the brain. Conversely, locations such as the mesencephalic and pontine reticular formations, locations in the brain stem important for control of eye movements, showed decreased MD. This decrease suggests what’s called “cytotoxic edema” where too much fluid builds up on the cellular level, causing swelling. Last but not least, several white matter tracts, which can be thought of as information highways in the brain, showed signs of swelling and inflammation as well (Newcombe, et al., 2021).
Together, these results suggest widespread “vasogenic edema” meaning there is too much fluid on the brain, causing swelling. These findings line up with autopsy reports suggesting “sepsis associated encephalopathy”, a severe immune system response causing damage to the brain, but do not explain the swelling in the brain stem (the mesencephalic and pontine reticular formations mentioned earlier) (Newcombe, et al., 2021). The researchers believe this could be one of two mechanisms causing these problems: First, what is called excitotoxicity, where excitatory neurotransmitters in your brain are in such high concentrations that they start causing damage. Second, is a direct COVID-19 infection of the brain. In one of the patients examined, there were moderate numbers of T-lymphocytes, a type of body immune cell which are not normally present in the brain, and active microglia cells, a type of immune cell which is supposed to be in the brain. These lymphocytes are thought to have infiltrated the brain through a weakness in the blood-brain barrier (Newcombe, et al., 2021).
These findings open a lot of doors when it comes to neurological research surrounding COVID-19. Not only does this paper suggest two possible mechanisms that could be causing these neurological issues, but it also provides a trail of breadcrumbs for future researchers to follow. It is both devastating and exciting news to hear of this research; It paints a more grim and far more sinister picture of COVID-19 than was initially thought, but is also a sign that we are making strides to figure out the specifics of the disease, and thus, defeat it. This sort of research is critical to clinicians and, in the grand scheme of things, saves lives. I look forward to seeing more of it in the future.
Citations
Newcombe, V.F.J., Spindler, L.R.B., Das, T. et al. Neuroanatomical substrates of
generalized brain dysfunction in COVID-19. Intensive Care Med 47, 116–118
(2021). https://doi.org/10.1007/s00134-020-06241-w
World Health Organization. (2021, February 24). Advice for the public On covid-19. from
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-pu
blic
