Understanding the Science Behind Covid Symptoms
We’ve seen many stories on social media by people who were infected by COVID-19, and the symptoms seem quite varied. From milder symptoms like cough, low-grade fever, and fatigue to others paint a more morbid picture of near-death experiences from the same disease. Today the death toll due to COVID-19 around the world is estimated to be 300,000 deaths. Despite measures that have been taken, the death rate continues to rise. Meanwhile, researchers are constantly working to better understand the disease and its culprit SARS-CoV-2, an RNA virus.
How a New infection progresses
The Virus enters cells by using a surface receptor known as the angiotensin-converting enzyme 2 receptors (ACE2-R). In a healthy cell, this receptor is simply part of the machinery responsible for regulating the body’s blood pressure. Due to its mode of entry, ACE-2 receptor-rich organs are more susceptible to invasion by the virus.
A new infection begins its journey in the nasopharyngeal cavity, where the virus uses the surface ACE2-Receptor to enter the cell and then replicates itself using the host cell's genetic machinery. Consequently, some patients will present with symptoms such as cough, loss of smell, and taste. When the body senses this pathogen has invaded, it responds via its innate immune system, which is essentially the body’s first responders; macrophages, cytokines, and neutrophils, resulting in an increase in body temperature.
If the body’s immune first responders fail to halt the invasion in the nasopharyngeal cavity, the viral activity continues onward to the lung another tissue rich in ACE2-R. The first thing the lung does after it realizes it has been invaded it to signal for help via its type 2 pneumocytes (which are also responsible for making surfactant). First-line responders like macrophages heed the call and release cytokines IL6, TNFα, and IL-1. These cytokines then prepare the way for the bigger guns to arrive by expanding the highway (vasodilation capillaries) and increasing the permeability of capillaries so that other defense soldiers like neutrophils can arrive.
Now, this is where the mechanism of lung tissue injury really starts to affect respiration. So just a quick pause to explain in very simplistic terms the physiology of the alveoli and capillaries.
The alveolus has 2 types of cells, the type I cell is responsible for the actual gas exchange when you breathe in oxygen, it is passed on to the red blood cell in the capillary adjacent to the alveolus. The second cell type is the type II cell responsible for producing surfactant which helps keep the airways open via surface tension.
Symptom: Fever, Shortness of Breath, difficulty breathing
So remember the macrophages show up and release cytokines IL6, TNFα, and IL-1? Well not only do these cytokines induce a fever, but they also go on to make the lumen of the capillary larger and more permeable. Of course, this is where things really start to go downhill. Because of the increased permeability, fluid begins to accumulate in the alveoli and dilutes the surfactant meant to keep your lungs open. Hence it becomes much harder to breathe and oxygen saturation decreases at this point. Another key player that pops into the picture is the neutrophils thanks to macrophages and their cytokines.
Now the problem with neutrophils is that they are akin to calling an army squad to contain anthrax contamination at a house party, and the squad’s response is to blow up the entire house… Overkill right!
That’s pretty much what the neutrophils do. They come in and kill any cells infected with SARS-CoV-2, which means fewer type I and type II cells meaning less surfactant and surface area available for gas exchange to occur. When this phenomenon is replicated in most of the alveoli, the syndrome is called ARDS (Acute Respiratory Distress Syndrome), and at this point, it is very difficult to breathe without a ventilator. In some cases, ARDS ultimately results in death.
Next phase systemic inflammation: fever, reduced blood pressure
Sometimes these inflammatory mediators, don't stay localized. So remember the neutrophilic army squad that blew up the house party. Well, some of these release cytokines made it out, but are now pumped up and turnt, and looking for the next party. So they carpool and get back onto the main blood circulation highway via the capillaries. I mean they have just been released and are really trying to live their best lives and continue the search for the next house party. Unfortunately, sometimes these mediators don't differentiate healthy from unhealthy tissues when they continue their attack.
The vasodilation and permeability will decrease the pressure in the vessels which will present as really low blood pressure when measured. This decrease in pressure in the vessels means blood can’t “pump along” to other tissues that need it. And if blood is unable to oxygenate the tissues the organs will begin to shut down. This is referred to as shock.
Another key organ affected is the kidney, and there are multiple ways it can progress:
- via Shock: not enough blood, goes to the kidney, no thanks to the cytokines, or in some cases an injured heart, leading to a condition known as a Prerenal Acute kidney injury.
- via Direct Injury by the virus: which will unfold in a similar pattern as what we observed in the lung. Because just like the lung the kidney has ACE2-Receptor-rich tissue.
- People with pre-existing chronic kidney disease, and a sequela of conditions like diabetes are also more prone to kidney failure and consequentially need dialysis.
- via clots: it has been observed that in some patients there is a higher occurrence of clot formation. This is further evidenced by the number of patients exhibiting lymphopenia (low white blood cells) and thrombocytopenia (low platelets) due to platelets being used up in clot formation.
Many things we still don't know
- What causes the clot formation that leads to strokes in some patients?
- Why is there a higher rate of morbidity in men vs women?
- How are patients on ARBs and ACEI affected?
- Why is SARS-CoV-2 so much more infectious than MERS and SARS
As the answers to these questions are discovered I will write a new article on them. Also, be sure to follow as I delve deeper into why the virus presents so differently and its predilection for the kidney and heart in upcoming articles.
