Hiding will show: scientists have discovered a new mechanism of mutation of the coronavirus

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Russian scientists have discovered a mechanism for the escape of coronavirus from human cellular immunity, which can lead to the formation of new strains. Previously, it was known that SARS-CoV-2 can only evade antibodies. New discovered abilities are based on the ability to mask from the so-called antigen-presenting molecules. The data was obtained thanks to a detailed study of the case of a long-term covid in a patient with weakened immune defenses: her illness lasted almost a year. According to experts, the obtained scientific results will help predict the emergence of a new class of virus strains and create effective means of combating them.

318 days

Skoltech scientists have discovered a previously unknown mechanism for the emergence of coronavirus mutations, through which new dangerous strains of SARS-CoV-2 can arise. The study showed that the causative agent of COVID-19, adapting to the immunity of the host, is able to acquire changes that allow it to elude human T-lymphocytes (a type of immune cell).

The immune system fights infection by producing antibodies and T-lymphocytes. How SARS-CoV-2 adapts to the first variant is known to scientists quite well, and how to avoid cellular defenses has been little studied. To understand them, experts examined the case of a patient whose body fought the infection for almost a year.

Photo: RIA Novosti / Alexander Galperin

“We decided to check whether the virus develops protection against T-lymphocytes, and for this we studied a case of long-term covid: the patient had a coronavirus infection for 318 days,” said Georgy Bazykin, head of the study, Skoltech professor. – It is important to note that in parallel she received anti-cancer therapy, the side effect of which is the suppression of antibody synthesis. This allowed us to observe the virus, which was left alone with T-lymphocytes. And our analysis showed that during a long infection, the coronavirus actually accumulated just such mutations that prevented the patient’s T-lymphocytes from recognizing it.

Under normal conditions, T-lymphocytes identify characteristic regions of the viral particle, called antigens. They, in turn, are demonstrated (presented) by specialized antigen-presenting molecules. From the entire individual repertoire of T cells, the body selects those that best recognize a particular antigen. This allows the immune system to subsequently deal with the virus. However, as the study showed, during a prolonged infection, the antigen can change due to virus mutation, and then the selected type of T-lymphocytes will stop working or the antigen will not be presented at all on the surface of infected cells.

This evolution of the virus genome occurred as a result of the pathogen’s attempts to adapt to the immunity of a particular patient. However, a more detailed analysis showed that the coronavirus thus acquired resistance not only to the protective cells of the studied patient, it also learned to partially evade the T-cell response in the human population as a whole. As scientists have found, the observed mutations successfully mask the virus from a number of antigen-presenting molecules common in humans.

Photo: Izvestia / Dmitry Korotaev

Scientists are worried that a new strain that has appeared in the body of a person with a weakened immune system will be able to break free and infect a large number of people.

“It is still difficult to judge how dangerous this class of mutant strains can be, but we will try to figure this out in future studies,” summed up Georgy Bazykin.

silent evolution

How well we know and understand exactly how the coronavirus evolves will determine our success in the fight against further options. Mutations that allow to deceive cellular immunity are still insufficiently known, agreed with the authors of the study, radiology doctor, lecturer at the Moscow Institute of Physics and Technology Anna Khoruzhaya.

— The authors described the spectrum of mutations of the virus, giving the ability to avoid attack by T-cells. They believe that these changes may lead to the emergence of new epidemiologically significant variants of the infection. Patients with a weakened immune system can just become their foci. And this version of the evolution of SARS-CoV-2 definitely cannot be written off,” said Anna Khoruzhaya.

Photo: RIA Novosti / Vitaly Timkiv

The study of mutations of the coronavirus, which exists for a long time in conditions of weakened immunity of carriers, is of great interest, as it will allow finding new ways to treat COVID-19. And in the future, this will be able to reduce the burden on national healthcare systems, whose capabilities in the fight against infectious diseases are very limited, Stanislav Ostavnov, head of the laboratory for analyzing population health indicators and digitalization of healthcare at MIPT, is sure.

When the virus gets to a weakened person, SARS-CoV-2 remains in his body for a long time, and during this time the pathogen has time to develop its own defense mechanisms. The human immune system adapts to changes and again begins to fight the virus, it again develops defense mechanisms. This is repeated many times, and there is a natural selection of viruses that can elude immunity, explained Mikhail Bolkov, a researcher at the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences.

Photo: Izvestia / Dmitry Korotaev

“A variant modified in this way can successfully infect other people, since this path of evolution of the virus inside their bodies has not been passed, therefore, for their immunity, this is a completely unfamiliar strain,” Mikhail Bolkov said.

The fact that SARS-CoV-2 can evolve in the direction of escaping not only from antibodies, but also from T-cells in immunodeficient patients has long been assumed, but it is one thing to understand, another to prove, the specialist concluded.

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