A scanning electron microscope image of SARS-CoV-2 (yellow) isolated from a patient, emerging from the surface of cells (blue/pink) cultured in the lab. Image: NIAID/Flickr, CC BY 2.0.
Our lungs have a basic functional unit called the alveolus (plural: alveoli; Latin for ‘small cavity’), where the oxygen from air diffuses into the blood capillaries while the carbon dioxide from the blood diffuses into the air, to be expired subsequently.
These small cavities are lined by a substance called a surfactant. A surfactant is what prevents the walls of alveoli from sticking to each other – just like how a detergent works to remove grease from your hands. This is necessary to prevent the alveoli from collapsing at the end of a breathing cycle, when the air pressure inside the lungs decreases due to the expiration of air.
In the absence of a surfactant, every breath you take will be as hard as a newborn breathing for the first time: the child’s lungs are collapsed and need to be inflated with air.
Role of ventilators
This is exactly what happens when the quantity of the surfactant is reduced for some reason. This can be due to a genetic defect in the cells involved in producing the surfactant or because something has injured these cells. This agent of injury can be environmental, like air pollutants, smoke and pathogens – such as those that cause pneumonia.
The damage can also be collateral, inflicted by a hyperactive immune response directed towards an unrelated immunogen. This is why it’s very much possible for a patient with acute pancreatitis to develop acute respiratory Distress and require a ventilator.
SARS-CoV-2, the virus whose infection causes COVID-19, uses ACE2 receptors to enter cells. Unfortunately, the cells that produce the surfactant have some of the highest concentrations of ACE2 receptors in the human body, and SARS-CoV-2 uses these receptors to enter and damage these cells. The immune system responds, sometimes too aggressively, against these virus-infected cells and releases a barrage of chemical messengers that could exacerbate the damage.
When the surfactant level in the alveoli drops, they end up collapsing at the end of a breathing cycle, and the need for subsequent inflation in the next breathing cycle increases the stress on our breathing muscles considerably. To prevent redundant blood circulation through collapsed alveoli, where minimal oxygen diffusion occurs, the blood vessels supplying these alveoli constrict and redirect the blood to functional alveoli.
When the labour of breathing increases, our breathing muscles are forced to work harder. Depending on the severity of damage, the muscles can handle the extra stress for a while, but they will inevitably tire and render the person unable to breathe. Supplying these people with air containing a higher concentration of oxygen has been known to help, especially if their distress level ranges from mild to moderate. But when the distress is too high, a ventilator is required.
Ventilators are devices designed to pump air into the lungs to facilitate oxygen diffusion into the blood. They can be non-invasive, of the sort commonly used to help treat snoring, or invasive, which require the endotracheal tube to be placed inside the windpipe.
Modern ventilators allow doctors to control the air volume and pressure as well as oxygen concentration, adjust the rate of breathing and even prevent premature lung collapse. In essence, they can work like artificial lungs, buying time for the immune system to fight off the pathogen and for the lungs to heal.
This said, COVID-19 pneumonia is a bit different.
The lung vasculature
Doctors were caught unawares when the first cases of COVID-19 pneumonia came to light. Although a majority of patients recovered on their own, a significant minority manifested an unusually rapid progression – from relatively mild symptoms to severe respiratory distress.
Also, while conventional ventilation strategies helped, factors influencing ICU death and recovery varied widely, suggesting differences in the ventilation strategy were having an effect. Some patients, at least in the early stages, were disproportionately short on blood oxygen despite normal respiratory mechanics and mild changes on a CT scan.
A key insight was that the ACE2 receptors are not limited to the lung tissue proper but are also present in the lung vasculature – a fact medical researchers had identified a decade ago, during the SARS pandemic. So an idea arose that SARS-CoV-2 was affecting the lung vasculature as well as impairing the essential compensatory blood redirection from collapsed alveoli, resulting in large volumes of redundant deoxygenated blood flow.
The virus was also found to increase the blood’s tendency to coagulate. This in essence shunted blood flow, pulling down the supply of oxygen to the blood and eventually to tissues around the body.
Based on their extensive experience early on in Italy, one group of researchers suggested that this reaction to COVID-19, called type 1, or type ‘L’ for low lung elastance, should be treated with caution. They wrote that “avoiding doing too much is of higher benefit than intervening at any cost” – in order to stave off ventilator-induced lung injury while at the same time providing anticoagulation drugs, high-concentration oxygen and other supportive strategies to increase the time available for the immune system and the lungs.
The other phenotype, called type 2 or type ‘H’ for high lung elastance, was to be treated with traditional strategies for acute respiratory distress.
Obviously both phenotypes are different parts of the same spectrum and one can evolve into another. It was even possible for one patient to have features suggestive of both.
COVID-19 treatment continues to evolve as a whole with new insights into drug therapy and immune response. All we can hope for now is that this evolution is faster than that of the virus and the pandemic.
Dr Kushagra Agarwal is a physician with training in general medicine.
This article is available to republish under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.