How Does Coronavirus Get You Sick?

This is what SARS-Cov-2 does to your body and why it kills even healthy, young people. It’s also why the Maduro-recommended Cuban interferon might be dangerous.

Photo: Kennyjo

Patients with coronavirus can have a wide range of symptoms; while most people will have a hard time differentiating COVID-19 from the common cold, many others will require oxygen and even the use of a ventilator to stay alive. It’s also true that while the disease is typically more severe in older patients, young people can also get seriously ill.

To understand why some folks get sicker than others, and especially to devise potential ways to treat those patients, we need to understand the mechanisms behind the disease. 

Patients who die of COVID-19 usually develop a condition called Acute Respiratory Distress Syndrome (ARDS), characterized by the inflammation of the terminal segments of the lungs, called the alveoli. The alveoli are basically a thin membrane that separates air from blood vessels, and the place where oxygen(O2) from the air we breathe is exchanged with the carbon dioxide (CO2) produced by our normal metabolism. 

To understand why some folks get sicker than others, and especially to devise potential ways to treat those patients, we need to understand the mechanisms behind the disease.

In ARDS, inflammation (which may be caused by many different things) leads to fluid accumulation in the alveoli, thickening the membrane and making the gas exchange much more difficult. The use of oxygen can help in this stage but, in some patients, mechanical ventilation, which modifies the volume and pressure of air sent into the lungs, is needed to keep the alveoli open and enough oxygen into the bloodstream.

Upon its entry into the body, SARS-Cov-2 uses one of its proteins to bind a receptor present in some lung cells. This receptor is the Angiotensin-Converting Enzyme 2 (ACE2), which normally helps regulate blood pressure and is a target of commonly used antihypertensive drugs. The concentration of this enzyme tends to increase with age, which may ease virus entry to the cells. 

Once SARS-Cov-2 enters the cells, it starts producing the proteins it needs to survive. In a SARS-Cov-1 infection (which caused the SARS outbreak of 2003), some of these can block the production of key regulatory molecules: interferons. A similar situation may occur in COVID-19.

Interferons are essential to control the initial replication of the virus, which is the reason why some of them, including Interferon alfa, the “Cuban miracle drug,” have been proposed as a potential therapeutic agent. Nonetheless, interferons can also trigger the production of many other proinflammatory molecules, called cytokines. 

In COVID-19, this seems to play a key role. Although the production of interferons is initially reduced, in later stages, after the virus has replicated in large numbers, these molecules can be produced again. The delayed interferon production fails to suppress viral replication and can lead to severe inflammation, which causes ARDS and myocarditis (inflammation of the heart).

This is just one of the reasons why the interferon treatment should be considered experimental. While early administration might be useful, it could worsen the symptoms later on. Meaning: a better understanding of the drug’s role in the pathogenesis is needed before giving it to patients routinely.

This is just one of the reasons why the interferon treatment should be considered experimental. While early administration might be useful, it could worsen the symptoms later on.

This theory also matches reports suggesting that inflammatory responses are increased in patients who died of COVID-19. These people had high levels of some of these cytokines, like interleukin 6 (IL-6); elderly patients, who usually have underlying heart and lung problems, might have more trouble dealing with the dysfunctional inflammation, therefore being more prompt to develop severe disease and die. But due to particular genetic traits, younger patients could also develop particularly strong “cytokine storms” that lead to severe disease.

Most information regarding COVID-19 pathogenesis is based on what’s already known about SARS and MERS, but given the similarity of these viruses, similar mechanisms are probably true for SARS-Cov-2, too. Further research (which is currently occurring at a never-before-seen speed) will probably help find more potential treatments and determine which of the existing ones can be safely used in COVID-19 patients.

Juan Carlos Gabaldón

Medical doctor from Merida, currently studying Medical Parasitology at the London School of Hygiene and Tropical Medicine