Coronavirus mutations: is it true that strains of SARS-CoV-2 are becoming more dangerous

As the COVID-19 pandemic develops, the SARS-CoV-2 coronavirus that causes this disease continues to mutate, that is, change. This means that its properties also change, and new strains may well pose a great threat, for example: it is easier to transmit from person to person or cause a more serious disease, writes Air force.

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Cases of re-infection have already been described, when a recovered person fell ill again having met with another version of the same infection. Moreover, it is known that the disease in this case can proceed even in a more severe form.

What strains of the virus are known to scientists at the moment and how dangerous are they? And could a potential vaccine protect against all known variations of the coronavirus?

What is a strain

Each virus has its own genome - a unique specific sequence of DNA or RNA.

The SARS-CoV-2 genome is a long RNA sequence consisting of approximately 30 thousand characters (nucleotides), following each other in strict order. This order can change: during the assembly of each new copy of the virus, an error may occur in any of these links - the replacement of one nucleotide with another, and as a result, the code of the entire chain will change slightly.

In each new “host,” the virus genome changes slightly. These changes may be very minor, but they make it possible to establish a connection between infected people or trace the path that the virus has taken.

When scientists use the word “strain,” they mean a genetically distinct branch of the virus that differs by one or more mutations from its “parent.” The difference may be only a fraction of a percent of the entire genome, but each new RNA sequence can give rise to a new branch of the virus, that is, a new strain.

The rate at which genetic changes occur varies among viruses—and SARS-CoV-2 mutates relatively slowly. Most of the genomes of this virus differ from each other in a small number of point substitutions, and the number of differences from the original variant does not exceed 30 by almost 30 thousand nucleotides.

What strains of coronavirus exist

There are seven main strains of the new coronavirus; they are designated by the letters GR, G, GH, O, S, L and V. It all started with the L strain, which was discovered in Wuhan, China in December 2019. However, now it is gradually disappearing.

The rest of the strains are distributed unevenly around the world: on each continent, the most common, as a rule, no more than two main variations. Their spread can be observed on the Nextstrain interactive map compiled by scientists, which tracks virus mutations.

The Russian research center Vector reported in October that it had identified more than 80 mutations of the coronavirus in the country. But mainly two strains are widespread - European and Asian, Rospotrebnadzor reported. Moreover, the latter was brought not from China, but from other Asian countries.

These two strains are found in 99% of the studied samples in Russia, the department said.

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How the virus mutated in Russia

“The total number of mutations that have been collectively identified in the sequenced genomes of the SARS-CoV-2 virus amounts to many thousands, but only a few of them have been fixed and are stably inherited,” Rospotrebnadzor explains. Now there are about 22 such single mutations; they occurred in January-March of this year. Later, new strains were no longer widely distributed, the department believes.

At the beginning of the epidemic in Russia, three main groups of mutations were consistently recorded in the genome of the virus, which formed, according to a study by Rospotrebnadzor, “three branches of evolutionary development.” By the end of March 2020, the development of these three areas was slowing down - and the main circulating strains in the country were strains with a mutation in the ORF1b (P314L) and S (D614G) genes.

These two mutations were the most significant permanent change in the genome of the SARS-CoV-2 virus, the study highlights. In Rospotrebnadzor, it is believed that a mutation in the S gene is associated with a decrease in pathogenicity (the ability to cause disease by penetrating into the body). The department notes that this can be explained by the improvement in the treatment of patients during the pandemic.

The effect of a mutation in the ORF1b gene (P314L) is still poorly understood.

“Viruses mutate constantly, but coronaviruses mutate much more slowly compared to other RNA viruses,” explains Lyubov Kozlovskaya, head of the laboratory of polio and other enteroviral infections at the Federal Scientific Center for Research and Development of Immunobiological Drugs named after. M.P. Chumakova.

“Despite active circulation around the world, SARS-CoV-2 has changed less than 0,1% from the virus originally isolated in China 11 months ago. Major changes were identified in the early months of the spread, and the variants of the virus currently circulating widely are similar to those isolated in the spring,” she says.

Strain S (D614G) is now the object of close attention of scientists. It was first identified in August in Indonesia; then it was reported that this strain was allegedly 10 times more infectious than the original strain of the virus.

Some studies, which are still at the preprint stage (that is, not peer-reviewed or published in scientific journals), conclude that this mutation may indeed have a higher infectivity and a higher viral load when infected with this strain. But there are no final conclusions on this matter.

“The virus quite quickly acquired a replacement in the surface protein of the virion S (spike), which increases its contagiousness (the ability of infectious diseases to be transmitted from sick organisms to healthy ones. - BBC), but does not aggravate the course of the disease,” comments Kozlovskaya. According to her, other differences in virus strains are minimal.

The first variants of the virus with two mutations common in Russia were identified at the end of January in China, then in Australia. In February, these variants were detected in most Western European countries, Saudi Arabia, the United States, Canada, Mexico, Brazil, Morocco and Senegal.

A detailed comparison of the genomes of the virus in Russia and foreign countries suggests that strains imported from Western Europe in March and April 2020 are circulating in the country, Rospotrebnadzor notes.

“[The coronavirus] has mutated very little during these nine months and has not changed in those loci that are responsible for the manifestations of the epidemic process, for its, so to speak, aggressiveness and anger,” Anna Popova, head of Rospotrebnadzor, said last week. The department believes that the virus has a low ability to mutate - it accumulates only about two point substitutions per month, that is, about 24 mutations can occur in a year.

“The distribution of the main virus variants circulating in Russia is generally similar to that in Europe. Some differences are observed, but we have no reason to believe that these differences somehow change the clinical course or epidemiology of COVID-19 in Russia compared to European countries,” says Kozlovskaya from the center. M.P. Chumakova.

Rospotrebnadzor, in response to a request from the BBC, reported that every month scientists from the State Scientific Center for Virology and Biotechnology “Vector” fully decipher more than 150 genomes of the new coronavirus. “The data obtained is used to analyze the relevance of the diagnostic test systems used, help identify imported cases, and assess the regional characteristics of the genetic diversity of SARS-CoV-2,” the department said.

Now sequencing of the genomes of viruses is being carried out and the accumulation of data in various laboratories around the world, including in the Chumakov center, says Kozlovskaya. Scientists, she said, will correlate the genomes of viruses with the clinical picture of patients from whom they are isolated, which will make it possible to shed light on the significance of the most common mutations.

Studying the impact of each specific mutation on the clinical picture of COVID-19 disease is difficult, she admits. Scientists will study the significance of each specific mutation for the structure of mutant proteins, as well as determine the role of these mutations in the development of clinical symptoms and lung damage in animal experiments.

Vector did not answer questions from the BBC regarding the process of studying coronavirus strains. There, as in FNTsIRIP im. M.P. Chumakov, have currently developed and announced new vaccines against SARS-CoV-2, which are awaiting clinical trials.

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Should you be afraid of mutations

The main questions that scientists face in connection with coronavirus mutations are the ability of the vaccine to form an immune defense that will be equally resistant to different strains. The issue of differences in the impact on the infected person is also important. For example, whether some strains may be more infectious than others.

From the statements of Rospotrebnadzor it follows that the mutations of the virus are not so terrible. But in the scientific literature, several cases of re-infection with the coronavirus have already been reported.

To recognize an infection as repeated, scientists each time check the genetic composition of the pathogen and make sure that the strain of the virus is different from the one that caused the disease the first time - otherwise it is impossible to say with certainty that this is a secondary infection and not a protracted primary case.

Dutch news agency BNO maintains a counter of all recurrent illnesses ever reported, each with a citation of the source. According to the agency, 24 cases of repeated infections are known in the world, one of them became fatal. An 89-year-old female patient from the Netherlands with cancer has died.

Re-infections have also occurred in Hong Kong, Belgium, the United States and Ecuador.

“Every day, almost 20 thousand cases of the disease are registered in Russia, some of them are associated with viruses that have been circulating in the country for a long time, some are with imported variants associated with infection with the virus in other countries, often very remote,” explains Lyubov Kozlovskaya. “Therefore, of course, the importation and subsequent isolation of a variant of the virus that has not previously been found in Russia is possible, as recently happened in Norway.” However, according to her, this does not mean an immediate change in the epidemiological situation with COVID-19.

In October, the Lancet published a study describing two cases of reinfection with coronavirus infection. One of the patients from Nevada, USA, after re-infection, the disease was more severe. The 25-year-old patient required hospitalization due to oxygen deficiency; computed tomography revealed that he had viral pneumonia.

Scientists found that he was infected with a different strain, genetically different from the previous pathogen. “Thus, past exposure to SARS-CoV-2 may not guarantee complete immunity,” the scientists conclude. They remind everyone that all people, whether they have previously been diagnosed with coronavirus or not, should take the same precautions.

Will vaccines be effective if the virus mutates?

It is known that the coronavirus mutates more slowly than the influenza virus: according to various estimates, two times slower or a third. Because of this, the coronavirus vaccine is “likely to be stable and effective for longer than the flu vaccine,” Julian Tang, emeritus associate professor and clinical virologist at the University of Leicester, suggested to HuffPost.

At the same time, it is not yet known how long the immunity acquired with the help of the vaccine will last, even if it works properly, the scientist recalls. The effectiveness of the vaccine may also depend on the individual characteristics of the body - just like the flu vaccine, Tang said.

So far, scientists are inclined to think that vaccines being developed around the world to combat the first strains of the new coronavirus will be just as effective against new mutations. A study by Australian and American scientists, which was carried out using computer simulations and experiments on ferrets, was published on October 8 in the scientific journal NPJ Vaccines. The animals were injected with a potential vaccine INO-4800 developed by the American company Inovio Pharmaceuticals.

Most of the vaccines being developed around the world were modeled after the original D-strain of the virus, which was more common among the sequences published at the start of the pandemic, the scientists explained.

Since then, the virus has mutated into the G strain, the variations of which are now dominant around the world. The researchers feared that this mutation would negatively affect the effectiveness of vaccines under development.

“Despite the D614G mutation in the spike protein, we confirmed through experiments and modeling that the vaccine candidates are still effective,” said study co-author Seshadri Vasan, a professor at the University of York.

According to the scientist, it was discovered that the most common strain G is unlikely to require frequent selection of new vaccines - unlike influenza, for which a vaccine for circulating strains is developed every year.

Since the differences between the strains circulating in Russia are minimal, they most likely do not have a significant effect on the structure of viral proteins, Lyubov Kozlovskaya is convinced from the Center. M.P. Chumakov. This, she said, makes it possible to create and use a COVID-19 vaccine that does not have to be redone every year.

Do not forget that none of the vaccine developments in the world have yet passed the third phase of clinical trials, which conclude about its effectiveness.

In Russia, the Gamaleya Center’s Sputnik V vaccine is currently undergoing this stage. Two other Russian vaccines are just preparing to pass this stage.

Only after these studies, in which tens of thousands of people will take part, it will be possible to draw conclusions about the resistance of the immunity to coronavirus formed by vaccines.

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