Mosialos: Why some people get more serious about the coronavirus and why men are more at risk

The research that has been carried out on how each patient experiences the lighter or heavier coronavirus, explains the professor of Health Policy of the LSE, Elias Mosialos in a new Facebook post.

In fact, Mosialos explains why men seem to be more at risk.

Elias Mosialos’ publication:

After the studies on coronavirus we see that we are facing a multisystemic disease related to the carrier / patient, the virus and the areas where humans interact. The heterogeneity of clinical trial results fuels basic research to decipher the complexity of the COVID-19 disease outcome by patient. In turn, basic research highlights laboratory testing of how individual genetic traits can affect a coronavirus patient.

But why are some patients more or less seriously ill with coronavirus?

In addition to the underlying diseases and age, which we already know negatively affect the immune response, from time to time various hypotheses have been formulated that could explain, in part, severe cases.

• these patients may have been infected with higher amounts of virus or a more infectious strain of SARS-CoV-2. Higher levels of viral load are generally associated with a more severe disease outcome.
• history of infections as a determinant of the severity of the disease. For example, as is often said, a previous infection with another coronavirus can be protective.
• the inevitable “transformations” in some cells that occur in individual humans. These genetic and epigenetic processes are responsible, for example, for increasing the incidence of herpes zoster for 50 years.
• Genetic predisposition can also cause severe COVID-19 illness in healthy children and adults.

Samples from hundreds of patients have been tested and show that very seriously ill COVID-19 patients may have some mutations in genes that are ultimately responsible for lowering the body’s defenses. In other words, these patients can become seriously ill due to genetic errors inherent in their own organism and due to the production of autoantibodies.

Clinical samples from more than 650 patients with severe COVID-19 were examined in more detail, including rare cases of young patients in intensive care or elderly patients in good physical condition but in a life-threatening condition due to COVID-19. The comparison group included clinical samples from more than 530 people with asymptomatic or mild infection. They initially looked for differences between the two groups in 13 genes known to be critical to the body’s defenses (the genes that govern type I interferons).

It became clear that a significant number of people with serious diseases had genetic changes in these 13 genes and about 3.5% of them lacked a functional gene, meaning they had inherent genetic defects. When also examining 987 patients with life-threatening COVID-19 pneumonia, more than 10% were found to have autoantibodies against the interferon I system at the onset of infection, triggering an impaired immune response.

Additional experiments showed that the patients’ immune cells did not produce detectable type I interferons in response to SARS-CoV-2. Most of them, 94%, were men.

So what did these two studies show?

• More than 10% of people who became seriously ill with COVID-19, regardless of their age and pre-existing medical history, had autoantibodies (that is, they do not attack the virus but the immune system itself) reducing the immune response.
• In another approximately 3.5%, the patients carried specific genetic mutations, which were identified.
• In both groups, the result is the same: patients have a reduced response through the type I interferon system.
• Whether the proteins have been neutralized by so-called autoantibodies or not produced in sufficient quantities due to a gene with limited function, their lack of action appears to be a common theme among a subset of COVID-19 patients whose disease has been so far mystery.

These findings show that autoantibodies are one of the main reasons why some people get sick and not the consequence of coronavirus infection. They also explain for the first time why some COVID-19 patients are more seriously ill than other patients their age. This paves the way for possible individualized treatment for these patients.

The results also provide the first molecular answer why COVID-19 mortality is higher in men than women.