Coronavirus: theories as to why covid-19 can kill young and apparently healthy patients

The severity of symptoms of covid-19, the disease that causes the SARS-CoV-2 coronavirus, varies greatly from case to case.

While 80% of those infected experience mild or flu-like symptoms or at the other end of the spectrum, there are those who end up with pneumonia and connected to a ventilator in the intensive care unit, where the prognosis not always optimistic.

The most critical cases generally occur in the elderly or with previous health conditions, such as hypertension, diabetes or coronary heart disease, among others.

However, day by day, fatal cases are reported where the victims are apparently healthy young men and women and even children.

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Why? How do you explain why these people who are not in the most vulnerable category become seriously ill or die of covid-19?

“That is the million dollar question,” Michael Snyder, a professor and director of the Department of Genetics at Stanford University in the United States, tells the BBC World how difficult it is to find an answer.

But although solving this puzzle is not an easy task, scientists suspect where the answer may come from (multifactorial, they say), and have begun to follow different lines of research to shed light on this mystery.

Understanding why people who are not obviously vulnerable succumb to the disease, they say, will allow those most at risk to be identified, new and effective treatments – including a vaccine – to be designed and existing drugs to be used

The genetic hypothesis

One of the theories that has been proposed and that is gaining weight is that of genetic predisposition.

This is based on the idea that our own genetic peculiarities could influence the virulence with which the virus affects our body.

A gene that can have an impact on the development of the disease is the one that encodes the ACE2 receptor, which allows the virus to enter the cell to replicate.

“It is not a new idea. From studies comparing twins and twins, we know that susceptibility to major infectious diseases in the world such as tuberculosis, hepatitis or malaria, varies in part according to genetic characteristics, “Stephen Chapman explains to BBC World, Respiratory disease specialist and Human Genetics researcher at the Wellcome Trust Center at the University of Oxford, UK.

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An example that several scientists, including Chapman, use to explain the weight of genetics, is that of the herpes simplex virus.

This is a widely distributed virus in the population that can cause blistered infections of the mouth or face, if it is one type, or sores on the genitals, if it is another.

“The vast majority of people exposed to the virus do not become seriously ill, but a small minority with a single genetic mutation develops herpetic encephalitis (inflammation of the brain), which can be fatal,” says Chapman.

A similar mutation, he says, could explain severe cases of covid-19 in young people.

A gene of particular interest is the one that encodes the ACE2 receptor (the angiotensin-converting enzyme 2 of the cell surface protein).

It is possible that the genetic variations that make people more vulnerable to covid-19 are found in genes linked to the immune system.

Located on the surface of cells in the lung and other parts of the body, this receptor is the gateway that the virus uses to invade cells in the airways and begin to replicate.

The gene that encodes this receptor is polymorphic: that is, it has a series of common variants distributed in the population.

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“The hypothesis is that if you have a particular variant, that can make it easier or harder for the virus to enter the cell, so it can make you more vulnerable or more resistant to the disease,” explains the expert.

In the opinion of Jean-Laurent Casanova, professor and researcher at Rockefeller University in New York, USA, these genetic variations (or, as he calls them, inborn errors), “can be latent for decades, until a infection by a particular microbe. “

For this reason, his laboratory is now investigating if this is what is happening with the new coronavirus.

Chapman believes that vulnerability will likely depend not on the variety of a gene but on several genes, added to factors acquired throughout life.

These variations, he notes, could be located above all in genes linked to the immune response.

The X chromosome

Another interesting aspect, says the researcher, is whether there are genes within the X chromosome that influence the response to the disease, since men seem more affected by the new coronavirus than women.

According to a study carried out in China, men are more vulnerable to SARS-CoV-2 than women.

One of the explanations that have been given in a study carried out in China is that this may be due to the fact that they have riskier lifestyle habits related to tobacco and alcohol.

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However, “Another possibility is that there is a genetic component, since there are many immunity genes that are on the X chromosome,” says Chapman.

“If there are a lot of polymorphisms or a rare mutation in the X chromosome genes, like men have one, while women have two, that would make them more vulnerable.”

Cytokine storm

In some patients with the more severe form of covid-19, what is known as a “cytokine storm” occurs.

Cytokines (or cytokines) are very aggressive substances that the immune system excretes to attack the virus.

But when the immune system is activated excessively, this proliferation of cytokines ends up attacking multiple organs including the lungs and the kidney, and this damage can result in the death of the patient.

According to Randy Cron, an expert from the University of Alabama, in the US, this lack of control occurs in at least 15% of people who fight any severe infection.

Several projects in different parts of the world are analyzing the link between the genetic characteristics of infected people and the degree of lightness or severity of the disease.

It is not known exactly why the immune system reacts in some people in this way, but the answer could also lie in the genes.

“We know that there are many common polymorphisms and rare mutations in the genes that control the immune system,” says Chapman.

“So some patients who die may have polymorphisms or mutations that predispose them to a more excessive inflammatory response.”

As a geneticist, Michael Snyder by no means underestimates the importance of genes, but he believes that in this case, there is another factor that could have more weight and that is environmental: previous contact with another coronavirus.

Exposure to another coronavirus

“It is very likely that in these cases,” Snyder tells BBC Mundo, “there is something that is sensitizing the immune system.”

In the opinion of Stanford geneticist Michael Snyder, exposure to another coronavirus that causes a common cold could be causing us to be more or less sensitive to the new coronavirus.

His suspicion points to “another coronavirus that is circulating and that has not been talked about much, called HCoV-229E, and that produces the common cold.”

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“We don’t know if having previously been infected with this common cold (which is obviously not as severe as covid-19) can make you more immune or, on the contrary, more hypersensitive,” says the expert.

“But I think it can have, for one side or the other, a very strong effect,” he adds.

“It is possible that many people have been infected in recent years (with that coronavirus) and do not know it, because they dismissed it as a simple cold.”

Viral load

Another cause of the severity of some cases may be the viral load at the time of exposure to the virus.

“We know from studies in China that those who care for patients with covid-19 are more susceptible than others because they are likely exposed to the virus every day, all day, during their work hours,” he explains. to BBC Mundo Alice Sinclair, virologist at the University of Sussex, in the United Kingdom.

The more exposure to the virus, the more opportunities for it to enter and replicate in our cells.

“But what we don’t know is whether that is because of the absolute amount of virus they are exposed to or the number of encounters they have had with it.”

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“In terms of viral load, the more exposure you have, the more chance the virus will have to infect your cells where it can replicate itself,” he adds.

The answer is not conclusive, among other things, due to what has recently been discovered about the viral load of the new coronavirus, such as the fact that an asymptomatic person can produce a large amount of virus.

That is, one can have a high viral load and not be severely ill or even have symptoms.

That is why maintaining social distance is one of the measures that both governments and health professionals emphasize the most to avoid the spread of the virus, says the researcher.

Finally, and beyond the host, the severity of the disease could depend not only on the host, but also on the virus itself, according to experts consulted by BBC Mundo.

Viruses are constantly mutating, and it is possible that there is a more virulent strain than another, although it has not yet been determined if this is the case for SARS-CoV-2.