Tuesday, April 14, 2020

COVID 19 and the central nervous system

1. What Defines a Brain Pathogen
2. Why SARS-CoV-2 Can Be a Brain Pathogen
3. Neurological Manifestations of SARS-CoV-2
   - 25th Feb: Neurological signs
   - 3rd Mar: Histopathological examinations
   - 4th Mar: Encephalitis case
   - 21st Mar: Encephalopathy case
   - 28th Mar: Recurrent seizures case
   - 31st Mar: Hemorrhagic necrotizing encephalopathy case
   - 1st Apr: Guillain-BarrĂ© syndrome case
   - 3rd Apr: Meningitis/encephalitis case
   - 8th Apr: Smell loss without nasal obstruction case
   - 10th Apr: Encephalitis case
4. How SARS-CoV-2 Can Invade the Brain
5. What Actions Are Needed
6. Why Things Aren’t So Straightforward
7. Is it the Immune System or Virus?


Why SARS-CoV-2 Can Be a Brain Pathogen

Weeks before clinical cases of SARS-CoV-2 brain infections were reported, Chinese and Pakistani researchers have already argued why the virus is capable of invading the brain:

Reason 1: SARS-Cov-2 is a type of coronavirus and most previous coronaviruses like SARS and MERS are known to infect the brain. It’s unlikely that SARS-CoV-2 is an outlier coronavirus.

Reason 2: SARS-CoV-2 enters a cell via the ACE2 receptor. Though this receptor is mainly expressed in the lungs, the brain has it as well.

Reason 3: Previously known coronaviruses infect the brainstem, which receives neurons from the lungs and respiratory tract. A damaged cardiorespiratory function of the brainstem likely underlies some cases of respiratory failure in COVID-19 victims.

Reason 4: COVID-19 patients show neurological symptoms such as confusion, nausea, headache, and loss of smell and taste. The last hints at a possible damaged olfactory system in the brain — and other coronaviruses are known to infect the olfactory bulb…

How SARS-CoV-2 Can Invade the Brain

Abdul Mannan Baig, MD and senior instructor at the Aga Khan University in Pakistan, is one of the earliest researchers to raise awareness about the neuroinvasive capacity of SARS-CoV-2.

In a recent paper published on 7th April, he outlined a few possible pathways by which SARS-CoV-2 can infiltrate the brain. “The hematogenous route appears to be the likely pathway for SARS-CoV-2 to reach the brain, but other routes to the CNS like across the cribriform plate of the ethmoid bone in proximity to the olfactory bulb should be taken into consideration in cases of early-phase COVID-19-affected patients who exhibit loss of smell and taste accompanied with neurological signs and symptoms,” Dr. Baig wrote.

Hematogenous means bloodstream wherein SARS-CoV-2 may enter the systemic circulation from the lungs and then reach and cross the blood-brain-barrier. The cribriform plate is where olfactory nerves of the nose cross and connect into the brain (i.e., the olfactory bulb of the limbic system); this route directly bypasses the blood-brain-barrier…

Why Things Aren’t So Straightforward

An important note is that most viruses do not normally cause brain diseases as their primary symptom. Herpes simplex virus, for example, causes cold sores but also encephalitis in some cases. Likewise for COVID-19 as respiratory disease, but can be a brain disease — causing meningitis, seizures, encephalitis, and encephalopathy — in rare instances.

In other words, viruses can infect the brain, but they may not cause brain diseases. Either because the brain immune system prevents it or the virus remains non-infective in the brain. In the latter case, the virus becomes latent (or sleeps) in the brain owing to the control of the immune system. As follows, when the immune system is suppressed, viruses have the chance to reactivate and re-cause diseases— more details here:  https://medium.com/microbial-instincts/first-case-of-covid-19-encephalitis-7b305fcfe9a8

Is it the Immune System or Virus?

Some scientists have even considered that brain diseases can be an “indirect result” of COVID-19. “It is also important to mention here that the neurological signs and symptoms observed in the COVID-19 cases could be a manifestation of hypoxia, respiratory, and metabolic acidosis at an advanced stage of the disease,” Dr. Baig himself argued against his propositions.

As mentioned above, Dr. Geraci also believed that the COVID-19-associated encephalopathy is due to the “cytokine storm” wherein the immune system damages the brain as collateral damage of fighting SARS-CoV-2. While this may be true, evidence of SARS-CoV-2 genes being found in the cerebrospinal fluid cannot be discounted.

“Although inflammation is critical for CNS pathogen clearance, lasting effects of immune molecules and pathogen by-products may represent an underlying mechanism of neurologic dysfunction,” explains Robyn Klein, MD and professor in the Departments of Medicine, Pathology & Immunology, and Neuroscience of Washington University. This means that an overdriven immune system and SARS-CoV-2 in the brain could both contribute additively to the development of brain diseases.


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