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The severity of symptoms of covid-19, a disease causing the SARS-CoV-2 coronavirus, varies significantly from case to case.
While 80% of those infected have mild or flu-like symptoms at the other end of the spectrum, there are those who end up with pneumonia and are connected to a ventilator in the intensive care unit, where the prognosis is not always optimistic
The most critical cases tend to occur in older people or in previous health conditions, such as, for example, hypertension, diabetes, or coronary heart disease.
However, deaths are reported day after day when the victims are apparently healthy young men, women and even children.
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Why? How do you explain why these people, who do not belong to the most vulnerable category, are seriously ill or die from covid-19?
“It’s a million dollar question,” says Michael Snyder, professor and director of the Department of Genetics at Stanford University in the United States, and tells BBC World how hard it is to find the answer.
But while it’s not easy to solve this riddle, scientists suspect where the answer might come from (multifactorial, they say), and began to follow different lines of research to shed light on this riddle.
According to them, understanding why people who are clearly not vulnerable to the disease will help identify those at greatest risk, develop new and effective treatments, including a vaccine, and use existing medicines.
Genetic hypothesis
One theory that has been proposed and which is gaining weight is the theory of genetic predisposition.
This is based on the idea that our own genetic characteristics can affect the virulence with which the virus affects our body.
A gene that can influence the development of a disease is a gene encoding the ACE2 receptor, which allows the virus to enter the cell for replication.
“This 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, partially varies depending on genetic characteristics, ”explains Stephen Chapman, BBC World Respiratory Specialist and human genetics researcher at the Wellcome Trust Center, Oxford University, UK.
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An example that several scientists, including Chapman, use to explain the weight of genetics, is the herpes simplex virus.
It is a widespread virus in the population that can cause blisters in the mouth or face if it is one type, or genital ulcers if it is different.
“The vast majority of people infected with the virus don’t get seriously sick, but a small minority with one genetic mutation develops herpetic encephalitis (inflammation of the brain), which can be fatal,” says Chapman.
According to him, such a mutation can explain the severe cases of covid-19 in young people.
The gene of particular interest is the gene encoding the ACE2 receptor (angiotensin-converting enzyme 2 of the cell surface protein).
It is possible that genetic variations that make people more vulnerable to covid-19 are found in genes associated with the immune system.
Located on the surface of cells in the lungs and other parts of the body, this receptor is the gateway that the virus uses to penetrate the cells of the respiratory tract and begins to multiply.
The gene encoding this receptor is polymorphic, that is, it has a number of common variants that are common in the population.
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“The hypothesis is that if you have a specific option, it can facilitate or hinder the penetration of the virus into the cell, which will make you more vulnerable or more resistant to the disease,” the expert explains.
According to Jean-Laurent Casanova, a professor and researcher at Rockefeller University in New York, USA, these genetic variations (or, as he calls them, inborn errors) “can hide for decades, until infection with a certain microbe.”
For this reason, his laboratory is now investigating whether this is happening with the new coronavirus.
Chapman believes that vulnerability is likely to depend not on the type of gene, but on several genes added to factors acquired throughout life.
These changes, he notes, can be detected primarily in genes associated with the immune response.
X chromosome
Another interesting aspect, according to the researcher, is whether there are genes in the X chromosome that affect the response to the disease, since the new coronavirus seems to affect men more than women.
According to a study in China, men are more vulnerable to SARS-CoV-2 than women.
One explanation given in a study in China is that it could be due to the fact that they have more risky habits related to tobacco and alcohol.
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However, “another possibility is that there is a genetic component, because there are many immunity genes that are on the X chromosome,” Chapman says.
“If the genes of the X chromosome have many polymorphisms or rare mutations, as, for example, in men, then one, and in women, two, this will make them more vulnerable.”
Cytokine storm
In some patients with a more severe form of covid-19, the so-called “cytokine storm” occurs.
Cytokines (or cytokines) are very aggressive substances that the immune system secrete to attack the virus.
But when the immune system is activated excessively, this proliferation of cytokines ultimately attacks several organs, including the lungs and kidney, and this damage can lead to the death of the patient.
According to Randy Crohn, an expert from the University of Alabama in the USA, this lack of control is found in at least 15% of people who are struggling with any serious infection.
Several projects in different parts of the world analyze the relationship between the genetic characteristics of infected people and the degree of ease or severity of the disease.
It is not precisely known why the immune system reacts in this way in some people, but the answer may 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.
“Thus, some patients who die may have polymorphisms or mutations that predispose them to a more excessive inflammatory response.”
As a geneticist, Michael Snyder in no way underestimates the importance of genes, but he believes that in this case there is one more factor that can be more significant and which is environmental: previous contact with another coronavirus.
Exposure to another coronavirus
“It is very likely that in these cases,” says Snyder BBC Mundo, “something sensitizes the immune system.”
According to Stanford geneticist Michael Snyder, exposure to another coronavirus that causes the common cold can cause us to be more or less sensitive to the new coronavirus.
His suspicion points to “another coronavirus that circulates and has not been talked about much, it is called HCoV-229E and causes a cold.”
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“We don’t know whether infection with this cold (which, obviously, is not as serious as that of Covid-19), can make you more protected or, conversely, more sensitive,” the expert says.
“But I think it can have, on one or the other hand, a very strong effect,” he adds.
“It is possible that many people have been infected in recent years (by this coronavirus) and are not aware of it because they rejected it as a common cold.”
Viral load
Another cause of the severity of some cases may be viral load during exposure to the virus.
“From studies in China, we know that those who care for patients with Covid-19 are more susceptible than others because they are likely to be exposed to the virus every day, all day, during the work day,” he explains . BBC Mundo Alice Sinclair, virologist at the University of Sussex in the UK.
The greater the exposure to the virus, the more opportunities it has to penetrate and multiply in our cells.
“But what we don’t know is because of the absolute amount of virus they encounter, or the number of encounters with it.”
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“In terms of viral load, the more exposure you have, the greater the chance that the virus will infect your cells where it can multiply,” he adds.
The answer is not final, among other things, due to the fact that it was recently discovered about the viral load of a new coronavirus, for example, due to the fact that an asymptomatic person can produce a large amount of the virus.
That is, a person may have a high viral load and not be seriously ill or even have symptoms.
That’s why maintaining social distance is one measure that governments and healthcare providers emphasize in order to avoid the spread of the virus, the researcher says.
Finally, according to BBC Mundo experts, the severity of the disease can depend not only on the host, but also on the virus itself.
Viruses constantly mutate, and it is possible that there is a more virulent strain than another, although it has not yet been determined whether this applies to SARS-CoV-2.
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