Keep the pocket wider

Then the immune system will easily deal with the coronavirus

Yuri Drize, "Search"

The year will not end yet, and responsible, health-conscious citizens will be able to come to the polyclinic and donate blood for DNA analysis. What for? To know if covid still overtakes them, how the disease will proceed, hard or easy. And the method developed at the Faculty of Biology and Biotechnology of the Higher School of Economics will help them understand this. Says one of the authors of the novelty – junior researcher Stepan Nersisyan:

– It is known that covid is different for everyone. Some carry it asymptomatically and do not even suspect about the illness they are experiencing. It is difficult for others, up to getting into intensive care. There is an answer to the question of why this is happening. One of the hypotheses recognized in the scientific world claims that the disease is difficult because of the genetic characteristics of the human body. Their DNA is arranged in such a way that the immune system is not able to effectively recognize covid. So, it is necessary to investigate the coding proteins of the genes responsible for the cellular immune response. And our group took up this task.

– But how to solve it if there are thousands of genes in the DNA?
– Yes, there are about 20,000 of them, but we are interested in only three known genes responsible for the immune response. At the same time, they are subject to various mutations, and it depends on them how the immune system reacts to the invasion of the virus.

– In your own words: if the immune system is strong, it rejects the virus, and the weak one gives up before it?
– Yes, you can say that. With a successful set of mutations, the immune system will easily detect the virus, attack it with all its might, and the disease will proceed almost imperceptibly.

– It turns out that everything is known, the method itself asks for your hands?
– In fact, of course, not so. Yes, the presence of three genes in the genome is not a mystery. But it is not known how much the flow of covid depends on the features of their device. It is clear that there should be a connection, but there was no experimental confirmation of this. And more. There are two copies of the genes we are interested in in the human body – six in total. And for each there are approximately 100 variants of various mutations. It turns out that 100 in the sixth degree is a lot! To get an answer to the question we are interested in, we need to sort out the entire array, all combinations and revise. Imagine how much time it would take! Experimentally, studying the condition of patients, this problem cannot be solved. Some groups of scientists before us compared the frequencies of individual alleles – different forms of the same gene – of a hundred people who were ill easily, and the same number – hard. However, in the case of covid, this approach did not yield results: the differences could not be identified.

It was necessary to develop an algorithm and make an integral assessment of the six's ability to respond to the SARS-CoV-2 virus. The idea was this: if we isolate one element from the six, then we will understand how well this allele "sees" the coronavirus. Then the obtained numbers can be added together and get an integral estimate for the whole six. (It took us about two months to develop the algorithm.) There are alleles that see the virus well, and those that can't cope with it. We conducted such a study: we put together six genes and concluded how well the human immune system sees the coronavirus. It is important to emphasize that the assessment obtained mathematically is associated with medical statistics – data on who got sick easily and who got sick hard.

Now a person can do a blood test and find out which of his molecules are with a "plus", which are with a "minus". If the immune system recognizes the virus, it means that a person will be easily cured of covid. If she does not see him, then the disease will be more difficult. The allele is a pocket – the virus particles are trying to get into it. It all depends on the shape of the pocket. If the virus penetrates it freely, then the immune response will be effective. If it is bad, the immune system will remain indifferent to the invasion.

– There is a well-known expression: "Forewarned means armed." Does it apply to this case?
– Absolutely. If, according to the results of the analysis, it turns out that a person can become seriously ill with covid, then first of all he will be recommended to get vaccinated. If he already has it, but about a year has passed since then, he needs to be tested for the presence of antibodies. And if they are not enough, it is better to get vaccinated again. And, of course, take precautions (this is especially important for opponents of vaccination).

– Will it be easy to make such an analysis?
– For DNA analysis in a regular polyclinic, blood will be taken from your vein. But the study itself will be conducted in a medical center or clinic, since it will require sufficiently complex equipment to determine the sequence of the three genes sought by sequencing. Today, this operation is still quite complicated, but it can be automated and put on stream. According to preliminary estimates, the analysis will cost no more than 5000 rubles. And within three days you will know the result.

– You published an article about your research, how did your colleagues react to it?
– An article co-authored with colleagues from the HSE, the N.I.Pirogov RNIMU and the Filatov Hospital was published by the journal of the first quartile Frontiers in Immunology (Shkurnikov et al., Association of HLA Class I Genotypes With Severity of Coronavirus Disease-19). It was released at the end of February. There are already responses, and there are quite a lot of them. The topic of the body's fight against the virus is not new to us. In September, we published an article about how the virus conquers the cell and how the body fights it. She has been quoted more than 15 times.

I would like to note that our faculty actively involves students in science. And here is the result: among the co–authors of the September article there are as many as four students (at the time of writing - freshmen). The faculty is expanding: a master's degree program will open in the near future. Therefore, we plan to continue to investigate coronavirus infection, increasing the range of areas under consideration.

– Can your research be used against viruses of other dangerous diseases?
– Yes, it is likely that our method will allow us to assess the severity of the course of other viral infections, for example, seasonal flu.

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