When it comes to covid-19, we already know what we’re in for after two years. At first, we were astonished to learn that the same virus might cause major sickness in some people while causing no symptoms at all in others.
Later, the emergence of new variants with distinct traits raised a lot of questions. Would we have to start all over? Would vaccines keep us safe? The solutions are coming in the form of data, but in actuality, we have a good tool for deciphering the two aspects of the problem: the changes in the virus and the human response: bioinformatics.
We’re getting better at analyzing both SARS-CoV-2 genomes and human genetics. The difficulty is to turn this potential into high-quality data that can help solve the healthcare dilemma.
A group of Spanish scientists has made significant progress.
A team from the Carlos III Health Institute’s National Center for Microbiology has published a study that identifies population groups around the world who respond less effectively to present SARS-CoV-2 mutations, as well as those that may appear in the future, based on genetic traits.
New research focuses on the component of the immune response dependent on T cells, which varies from person to person.
Despite the fact that the vast majority of the world’s population has a healthy immune system, some ethnic groups have genetic polymorphisms that make it difficult for them to deal with particular virus mutations.
The study published in the journal ‘PLOS Computational Biology’ finds certain communities in Africa and Asia, as well as minorities in Europe and the United States, and links them to coronavirus strains that potentially represent a concern.
The good news is that, as these same researchers explain in two other recent articles, immunizations give the protection that these patients may lack. As a result, according to Antonio J. Martn-Galiano, the study’s lead author, this new study is directed towards unvaccinated individuals, who are still very many throughout Asia and Africa.
“There are young people and athletes who, for genetic reasons, have an immune system that has difficulty ‘seeing’ a certain virus,” say the authors.
What do you mean by ‘seeing’ the virus? Once SARS-CoV-2binds to cells, it has to deal with innate immunity, but if this is not enough, adaptive immunity kicks in.
“That’s when the body takes it seriously,” says the researcher. On the one hand, there are the antibodies (humoral immunity) and on the other, the T lymphocytes (cellular immunity).
The team from the Carlos III Health Institute were especially interested in cytotoxic T lymphocytes, which recognize infected cells and induce them to commit suicide.
“This process changes a lot from one person to another, so we have identified the genetic differences between individuals,” they add. In other words, the researchers have analyzed “to what extent different people can ‘see’ the virus” and, therefore, neutralize it by analyzing several hundred thousand genomes, if the mutations of the virus are capable of evading that cellular immune response in people who have an already limited capacity to recognize the invader.
The researchers performed a computational analysis in which they merged viral data with global population genomic data. The cellular reaction works by detecting epitopes, which are tiny fragments of the virus. However, there may be distinct alleles, or mutations, among the human genes involved in this recognition that prohibit them from executing their job.
“The algorithm we use is efficient enough to predict which parts of the virus each person will recognize once we know which alleles they have,” explains Martín Galiano. They used 3,000 alleles, or genetic variants, in particular.
In reality, each person only has six, but “if you had the six variants that recognize few epithets of the virus, you would be almost unable to identify the virus conveniently, somewhat favored in inbred populations.”
As a result, even without vaccination and in the face of a first infection, at least 90% of mankind responds well to the covid virus, unless they have risk factors, such as other diseases or advanced age, that weaken the immune system. However, there are some ethnic groups who seem to have adapted better to combat other sorts of infections and, on the other hand, they hardly put up resistance against these viruses that are disseminated extremely quickly in huge numbers, says the specialist.
The study
To see if the risk can be geolocated, the study authors used geographic databases that show what type of human alleles are found in each country. Likewise, they introduced the sequences of the virus to identify the mutations that could most affect these populations. Crossing the data, they saw “hot zones” scattered around the world, places where many people live with genetic alleles that would make it difficult for them to respond to infection that coincide with the presence of mutations of the coronavirus that elude the action of the system immune. The populations are concentrated in sub-Saharan African and Asian countries, but they also constitute important communities in other continents, such as African Americans in the USA.
Thus, some variants of SARS-CoV-2 could be especially dangerous for populations with certain genetic variants. In fact, with very few mutations of the virus, they could lose all the protection offered by the cellular response. “We are not talking about the variants that have spread the most, such as alpha, delta or omicron. Those are very contagious versions of the virus. However, there are others that have found or could find their ecological niche in certain groups whose individuals would not be able to recognize the virus, which could generate locally very important epidemics. In reality, in that case, we would be facing an endemic variant of the virus, rather than a pandemic,” explains the author.
In an ideal world, everyone would be vaccinated and we would forget about these problems. However, in the real world, this research from the Carlos III Health Institute is still very useful.
“If, when sequencing the virus, you find a variant from which the population of a country cannot defend itself, it would be even more imperative to vaccinate everyone or intensify measures such as the mask or social distance,” points out the scientist.
In any case, as a result of this work, surveillance could be “universalized and automated”, he believes. “We already have the software, but the idea is to feed it with all the genomes that are sequenced on a regular basis. If we start to see that a variant becomes very recurrent in one part of the world without explanation, perhaps it is because it has found individuals with some genetic limitation in the cellular response,” he says. It is possible that said variant, outside of that ecological niche, has no relevance. However, it can wreak havoc on individuals who have little ability to defend themselves, and it can really break out at any time because a few mutations could change everything.
The vaccinated: absolute tranquility?
The computational analyses that warn about this danger, which would affect very specific populations of unvaccinated people, also show that the vast majority of those who have received the doses can rest easy: it’s almost impossible that a variant will emerge that circumvents the cellular and humoral protection provided by vaccines and, as a result, return us to the start of the pandemic. At least, that is the conclusion derived from two other recent articles published by the same research group.
One of them, published in the journal ‘Frontiers in Immunology’ at the end of January, looked especially at omicron mutations and compared them to the cellular responses elicited by existing vaccines, while also taking into consideration population genetic differences. Bottom line: there is adequate protection for the entire world’s population.
The other study, which was published in the same journal at the end of November, predicted that this would happen against any variant as computational analysis shows that the immune response of cytotoxic T lymphocytes generated by vaccines is powerful and strong enough to respond well to all versions of the virus.
“This virus is very dangerous because, by spreading so massively, it has many opportunities to generate mutations. However, to evade the cellular immune response, too many things would have to change,” comments the bioinformatics expert. In other words, “it is very difficult for a new variant to have a high transmission capacity and at the same time evade an immune system reinforced by vaccines. For example, omicron is very contagious but instead has lost the ability to cause severe disease with respect to, for example, delta,” he explains.
Therefore, the most vulnerable people are at risk.
“Generally speaking, the most susceptible people are in poor health. What happens with the elderly and immunosuppressed is not that they have a genetic problem, but that, among other things, their number of lymphocytes is lower and communication between sections of the immune system is more limited. When the immune response kicks off more complex processes, they don’t work as well in these people,” he says.
Therefore, the danger is in the most vulnerable people. “Generally speaking, the most susceptible people are in poor health. What happens with the elderly and immunosuppressed is not that they have a genetic problem, but their number of lymphocytes is lower and communication between sections of the immune system is more limited,” he says.
Source: 10.1371/journal.pcbi.1009726
Image Credit: Getty
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