I was happy to see a number downloading the free ebook on COVID-19. I had stated it is my intention to share this with as many as possible.
While the free e-book will be available from time to time, I want to share some of the chapters from the book so that even those who do not download the book, may find this useful.
In this post I want to share about the pathophysiology of the disease. From the time the book was written new information could have emerged which readers can share as feedback.
In this chapter, I would like to describe in a simple manner the pathological changes that are produced inside the lungs once the virus gets inside a human and multiplies. Very little was known from the initial autopsies conducted in China. Later pathologists in Italy carried out a larger number of autopsies and newer knowledge became available. Over time even newer knowledge is likely to occur. I am sharing what is currently known.
When an infected person expels virus-laden aerosol droplets and someone else inhales the SARS-CoV-2, it enters the nose and throat especially the epithelial lining of the nose. The cells there are rich in a cell-surface receptor called angiotensin-converting enzyme 2 (ACE2). These help in producing angiotensin which normally helps regulate blood pressure.
When the virus encounters an epithelial cell in the nose, the spike proteins on its surface stick to the ACE2 receptors of the host epithelial cells, which allows the virus to gain access and replicate. These virus act in a highly selective manner, and that it is dependent on certain specific human cells in order to spread and replicate,”
Once inside, the virus hijacks the cell’s machinery, and starts making numerous copies of itself and also starts invading new cells. As the virus multiplies, an infected person may shed copious amounts of it, especially during the first week or so. Symptoms may be absent at this point or the patient may develop a fever, dry cough, sore throat, loss of smell and taste, or head and body aches. The natural immunity of the individual in most individuals would overcome the virus and the individual may pass off as an asymptomatic or subclinical individual. This is the mildest and may be considered as the initial or phase 1 of this disease.
If the immune system doesn’t beat back SARS-CoV-2 during this initial phase, the virus then marches down the trachea and bronchi. This is considered the second phase or the second window of opportunity to ‘kill’ the virus. The mechanism is similar to that in the nose with the virus sticking the ACE2 receptor cells. The symptoms of cough and fever may be more than in the first phase. Many individuals with COVID-19 without any risk factors would be able to come out safely even in phase two with the help of natural immunity.
If it passes beyond this level to attack the lungs, it can then turn deadly. The thinner, distant branches of the lung’s respiratory tree end in tiny air sacs called alveoli, each lined by a single layer of cells that are also rich in ACE2 receptors. In between this layer of cells are tiny capillaries, which are tiny blood vessels. Carbon dioxide in the blood is exchanged for the oxygen in the alveoli. The oxygen is then carried to the rest of the body.
But as the immune system wars with the invader, the battle itself disrupts this healthy oxygen transfer. Front-line white blood cells of the immune system, release inflammatory protein molecules called chemokines or cytokines, which in turn summon more immune cells that target and kill both the virus, which is the normal function. and also, virus-infected cells (abnormal function in COVID-19).
At this stage, the patient begins to find it difficult to breathe. With supportive measures by providing oxygen supply through masks, many who reach this phase three, are able to overcome the disease and get well. Right from the time a patient is admitted, the lung function of oxygenation is measured by special tests. Oxygen saturation is measured by pulse oximeter with a sensor attached to a finger. Normal pulse oximeter readings usually range from 95 to 100 per cent. Values under 90 per cent are considered low. Additionally, the oxygen concentration is measured from arterial blood. Normal arterial oxygen concentration is approximately 75 to 100 millimetres of mercury (mm Hg). Values under 60 mm Hg usually indicate the need for supplemental oxygen.
For some unknown reason, the normal cytokine reaction gets into overdrive or hyper-reactive, resulting in what is called a cytokine storm. During a cytokine storm, the cells of the immune system attack and kill the virus as well as the normal alveolar cells of the lung. This leads to an accumulation of fluid and dead cells in the air sacs of the alveoli in place of air. This makes the patient struggling to breathe.
Some COVID-19 patients recover, sometimes with no more support than oxygen breathed in through nasal prongs or masks initially and then under pressure. But others deteriorate, often quite suddenly, developing a condition called acute respiratory distress syndrome (ARDS). Oxygen levels in their blood plummet and they struggle even harder to breathe. The patient has now reached what I would call the critical phase four.
By the time a patient reaches a stage of breathing difficulty, you can understand the changes that have taken place inside that person’s lungs. The patient is now put on a ventilator. There is very little functioning lung at the alveolar level. Even the oxygen pumped in by the ventilator is not adequately transferred at the alveolar level, because of the damage done by the cytokine storm. Oxygen does not reach in adequate concentration to different organs, resulting in failure of multiple organs, starting with the kidneys, the heart, brain, liver etc. resulting in death.
Italian pathologists who carried out a large number of autopsies of patients who died of COVID-19 observed that the cytokine storm created endothelial vascular thrombosis. The lung is the most affected because it is the most inflamed, but there is also a heart attack, stroke and many other thromboembolic diseases. Taking a viewpoint different from the earlier diagnosis, they conclude that it is not pneumonia but pulmonary thrombosis, that results from the cytokine storm. It was a major diagnostic error. This finding has an echo in the treatment which we shall soon see.
Another study in the US found that inflammation and systemic changes, due to the infection, are influencing how platelets function, leading them to aggregate faster, which could explain why the is increased numbers of blood clots in COVID-19 patients. It was discovered that the virus causes genetic changes in the platelets that also alter their interaction with the immune system and maybe the reason COVID-19 patients often suffer from severe lung damage.
Another, related change at this stage needs to be highlighted. Earlier, mention was made of ACE2 cells. These viruses, destroy these cells which help in producing angiotensin, a substance used for regulating blood pressure. With decreased angiotensin, blood pressure starts going upwards, which has to be managed along with oxygen for difficult breathing.
We have talked about breathing difficulty in COVID-19 individuals caused by four changes in the lungs. 1. This is caused by the swelling of the respiratory tract, which narrows the lumen of the wind pipe. 2. The infection fills the empty air sacs with fluid, preventing exchange of oxygen and carbon dioxide. 3. Thrombosis of the capillaries of the alveoli result in oxygen being not taken to different parts of the body. 4. Scarring of lung tissue takes place, which results in poor functioning of the lungs. All these result in difficulty in breathing.
As I mentioned all along, our knowledge around this disease is continuously changing. It cannot be said that we have reached an endpoint in our knowledge of this disease. However, this limited description of the pathology may help you understand what the research world is trying out with medicines that could at least restrict deaths first and then have medicines that could kill or control the viruses itself. If you have a relative who is admitted for care for COVID-19, you can understand what is happening to them when they indicate the various parameters of oxygen and blood pressure.
I will make the book available for free download again next week. Once I confirm the dates I’ll let you know. In the meantime here’s the link to the book.