In a previous article, “The Many Faces Of Covid-19”, we produced a graph that illustrated the Covid-19 and we also alluded to the many paths it could take from the respiratory tract, the cardio vascular system, the gastro-intestinal tract and many other parts of the bodies that can be attacked. Most severe cases have been related to the respiratory tract followed by complications often associated with other comorbidities.

Gastro-intestinal attacks when not followed by respiratory complications have proven milder. Symptoms can start as soon as 2 days but can be delayed as much as 14 days after infection. (in graph 5 days was used as the median figure). To understand the degree of severity of the disease in each case one must compare it to an invasion being repulsed by one’s defense cells Depending on the intensity of the initial attack and the robustness of one’s immune system the outcome can vary from asymptotic to critical cases sometimes followed by death.

Although it can be caught through the eyes by rubbing one’s face with infected hands, the normal initial infection occurs through the nose when a person inhales virus-laden droplet expelled by an already infected person. Although protected by a mucous membrane lined with rich tapestry of with blood vessels, the virus finds its way through the nasal passages and the sinuses to the epithelial cells where it finds a fertile ground of ACE 2 cell receptors.

Just as a module docks to a space station, the S protein with the help of a serine protease TMPRSS2 latches on the ACE2 receptor and enters the cell. Once inside, the virus hijacks the cell’s machinery, printing many copies of itself which exit the cell and proceed like storm troopers to invading new cells and form a massive invading army.

The first battle is on. How to kill all the invaders and stop the infection before they multiply enough to mount an attack to the throat, then the lungs and eventually reach some of the more vulnerable parts of the body? From the first moment a cell is invaded, it sends alarm by means of cytokines. The body mounts a response through inflammation enabling a rescue force of neutrophils and monocytes to emerge out of the tiny blood vessels in the region first hit by the pathogen. Within the neighbouring tissues as macrophages and dendritic cells gobble the virus. Activated macrophages secrete IL-12 a cytokine that multiplies the activity of NK (Natural Killer) cells that will try to contain the proliferation of the virus by killing as many as possible infected cells thus slowing down replication.

The dendritic cells will migrate to lymphoid nodes where they will trigger the start of the adaptive immune response, a longer pro which will deploy, after 4 weeks or so,  more specialised troops of specific antibodies and specific CD8 killer cells  that should theoretically kill the infection. But for the moment, the innate system has to take the fight on its own. In most cases after having visited the basal avenues covered with a barrier the virus has already reached the throat hence the sore throat. Symptoms at this stage can be, similar to an extreme flue, accompanied by a much more severe fatigue a combination of all the following: sore throat, headache, chills, sometimes with shaking, congestion or runny nose.

In some cases, the virus goes straight from the mouth throat straight to the endothelial cells of the stomach and it that case in addition to severe fatigue and sometimes headaches. Symptoms at this stage loss of smell or taste nausea or vomiting, abdominal pain and diarrhea. Some patients experience both gastrointestinal and respiratory infections. We will concentrate on the progression of the virus along the respiratory tract. The virus that has been able to multiply in excess of the destruction by an insufficient innate immune response either due to a weakened immune system response or a severe initial viral load and starts penetrating the lungs.

The lungs could be compared to 2 richly branched tree limbs, one on each side of one’s chest. The right lung has three sections known as lobes), and the left lung has two sections as lies above the heart. The air arrives through the trachea, a super-motorway that branches out to each lobe via the bronchi which are high density motorways.

Covid Development

The bronchi break up into smaller national roads called bronchioles. And at the end of each bronchiole is a small akin to a local exit road known as alveolar duct that connects to a cluster of thousands of microscopic air sacs, known as the alveoli. It is estimated that normal adult has 480 million alveoli that cover a surface that measures more than 100 square meters.

The battlefield becomes now much more extended. Just as for the nasal region, the innate system works overtime trying to stall the invasion and the multiplication off the virus. Here the situation is more complex as the lungs are the node of communication between two systems the respiratory system and the cardiovascular system. Both the lung’s alveolar epithelium and the blood vessel’s capillary endothelium are rich in ACE 2 receptors, one of the keys for entering the cells.

The performance of the lungs is now hampered as the virus attacks the air sacs on two sides. On the respiratory side, as the virus multiplies, pneumonia develops localised inflammation of the air sacs filling with pus or fluid that impairs the gas exchanges within the alveoli. In addition, the virus destroys the air sacs epithelial cells air sacs thus reducing the alveolar surface and further impairing the supply of oxygen and the evacuation of CO2 to and from the heart. On the capillary side it attacks the vessels that become damaged eventually resulting in blood clots that further reduce the flow of oxygen to the body organs.

 As more cells are infected and the virus multiplies, the innate army is in danger of becoming overwhelmed and the reinforcing troops from the adaptive system are days if not weeks away. Depending on the viral load , the robustness of the immune system patient and the comorbidities of the patient the lungs can become so damaged that fibrosis can devastate the lungs and multi organ failure ensues due to hypoxia (insufficient supply of Oxygen). This can happen depending on the age of the patient and his underlying conditions before the arrival of the reinforcing troops from the adaptive immune system.

For others, the attack is less violent, and the damages occur at a slower pace enabling after some 4 weeks after infection, the specific antibodies and cytotoxic cells arrive on the scene of the battle and clean up the battleground. For many they are alive but on a difficult convalescent route.

For unfortunate others, a cytokine storm develops which is a sign that the immune system has become dysregulated. killer cells attack self cells and destroy mistaking them as foreign enemies. Whereas the virus is no longer present, the lungs becomes so destroyed through hyperinflammation that many body systems such as the Renin-Angiotensin-Aldosterone System which links the liver, the kidneys, the lungs, and the blood vessels get out of sync. It is clear that even without going into the additional possible deficiencies of other organs, the dysfunction of this system coupled with the cardiovascular system problems are enough to produce an outcome of multi organ failure and death.

We shall attempt in a further article to review the possible mechanisms leading to fatal issues via the pulmonary impairment and the cytokine storm that both lead to multi organ failure.

By Digenis3 December 2020

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