You may have heard about the groundbreaking research conducted by researchers as a part of the RECOVERY trial, which looked at a number of medicines for the treatment of COVID-19. One of the drugs studied, dexamethasone, was shown to significantly reduce death in groups of patients with COVID-19, and since these results were published, it has seen almost immediate use in the NHS. This blog post is for interest only and is not to be taken for medical advice.
What is dexamethasone?
Dexamethasone is a steroid, which mimics a chemical synthesised and released by the body. Steroids are released naturally as a part of the body’s stress (fight or flight) response, which has effects on the immune system, energy production and general homeostasis.
Steroid is so-called due to the chemical structure of these molecules, which share a 4-ringed backbone (3 cyclohexane rings, and 1 cyclopentane ring). Steroids mentioned here refer to corticosteroids These differ to anabolic steroids which are sometimes used as an illegal performance-enhancing drug to boost sporting performance.
How would dexamethasone, a corticosteroid, help in COVID-19?
Over the last few months, COVID-19 has been extensively studied and a general understanding of how the initial infection progresses to symptoms has been established.
Stage 1: Virus
An individual can be infected with coronavirus via two main routes: droplets (directly from the respiratory tract of an infected individual) or fomite (an object which becomes contaminated with the virus and transmits this to another person).
The virus itself contains molecules which bind to cells in the lung (called pneumocytes or alveolar cells) and can be delivered to the lungs via direct inhalation or carried via the bloodstream. Once in the lungs, the virus enters the alveolar cells and hijacks the cellular machinery in order to produce additional copies of the virus.
During this process, the viral cells die, releasing the copies of the virus, as well as cytokines. Cytokines are a class of proteins that help cells communicate, which include interferons and chemokines. These molecules trigger an inflammatory process which recruits immune cells, as well as stimulating nerve endings in the lungs leading to a cough reflex.
Definitions
- Interferons – cytokines released in viral infections
- Chemokines – cytokines which attract other cells, commonly immune cells
Stage 2: Inflammation and the immune response
Inflammation refers to the process by which your body fights in order to heal itself. This is however not a specific response and damages structures that are in the vicinity, including alveolar cells. Alveoli (small air sacs within the lungs that help to increase the surface area for gas exchange) may also lose their elasticity and structure, impairing gas exchange.
These processes contribute to hypoxaemia (low oxygen in the blood), indicative of poor gas exchange (exchange of carbon dioxide with oxygen in the blood), and is a common sign seen in patients with COVID-19. Chemokines also have the additional effect of making blood vessels more “leaky”, allowing cells to migrate from blood vessels to the lungs more easily. In doing so, fluid in these vessels can escape into the lungs – causing pulmonary oedema (“water in the lungs”), further impairing gas exchange.
It is important to note that cytokines have an effect on other organs including the heart, liver, kidneys and brain, as well as muscles and blood vessels. This explains the multisystemic impacts of COVID-19.
Where does dexamethasone come in?
The RECOVERY trial showed that dexamethasone reduced mortality by up to one third in patients who required ventilatory support for their breathing, and by a fifth for patients receiving supplemental oxygen (oxygen at a concentration higher than that in atmospheric air).
So should everyone be prescribed dexamethasone?
As dexamethasone is an anti-inflammatory drug, it dampens the effects of the immune system. This can be beneficial when the inflammation is excessive, to prevent further damage to lungs and other organs. However, in early stages of the disease, the immune response is a beneficial and necessary force in the fight against the virus. Furthermore, as with any medication, dexamethasone has adverse effects, so its use should be considered in relation to potential benefits and these effects.
Summary
The RECOVERY trial investigators should be applauded for their tremendous efforts during challenging times. Further research will be needed to confirm these findings in a broader population, as well as to optimise the timing, dosage and route of administration for this treatment.
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