Evolution of SARS-CoV-2
How do new strains appear and which of them are dangerous for us today
Since the beginning of the pandemic, scientists have been examining samples of SARS-CoV-2, the causative agent of COVID-19. Some strains of the virus are much more easily transmitted from person to person, others may have a higher lethality. What are the strains, how many of them can there be and do vaccines help from all? Post-science asked virologist Lyubov Kozlovskaya about this.
What is a strain?
A strain is a virus sample isolated and fixed in laboratory conditions, having certain unchangeable properties. Virus strains are not analogous to species in other living beings. All the strains of SARS-CoV-2 obtained by scientists are not new viruses, but varieties of the same virus.
Some strains are called prototypical, exemplary, and all other strains are compared with them to establish the degree of their proximity.
A widespread group of viruses will always have certain similarities, and it is these that are fixed by analyzing specific strains. Individual characteristics of strains can reasonably be extrapolated to genetically similar samples.
By themselves, the strains do not circulate in nature, they exist exclusively in laboratories. And in nature, viruses spread that are similar in gene sequence to the prototype sample in the laboratory.
How do new virus variants appear?
Viruses cannot carry out vital activity outside the cells of an organism. However, just like other organic beings capable of reproduction, viruses have a genetic code – a sequence of nucleotides in the form of RNA or DNA that determines their properties and characteristics.
The process of division (replication) of the genome inevitably entails inaccuracies and errors when copying mutation genes. Some errors may become fixed and begin to be transmitted in generations (inherited), which, in turn, may lead to the appearance of a variant of the virus with new properties.
How fast does SARS-CoV-2 mutate?
Eukaryotic cells, including large organisms, have a protein system that allows you to correct errors made during genome replication.
Most viruses, especially RNA viruses, do not have such a mechanism, which is why they mutate at a high rate. As a rule, the average RNA virus that has infected at least a million people is very different from the original. For example, if one of the polioviruses were in conditions similar to SARS-CoV-2, it would have changed almost a third of its genome in the same time of circulation in the human population.
But the SARS-CoV-2 replication system can correct errors that occur during the copying of genomic RNA. This allows it to copy the genome with sufficiently high accuracy for the virus, but not infallibly. The genome of each specific virus will inevitably differ from the genome of the progenitor. In addition, the mutation potential of any coronavirus is limited by the size of its RNA. While most viruses fit into a sequence of 5-10 thousand nucleotides, coronaviruses have one of the longest RNAs: their genome consists of 29 thousand nucleotides.
Thus, SARS-CoV-2 is a rather slowly mutating virus in comparison with others. Today, humanity is dealing with a very small number of its varieties. There would be much more of them if some other type of virus got into the human population.
What contributes to the emergence of new variations of SARS-CoV-2?
Two parameters are important for the evolution of any virus: how actively the virus spreads and how long it exists in the human body. At the same time, there is no strict set of criteria that predetermine changes in the virus. Mutations are random, and not all changes are able to gain a foothold in the next generations. Now humanity does not have sufficient knowledge and resources with which we could predict such processes.
The key to the evolutionary success of SARS-CoV-2 was its very high transmissivity, that is, the ability to be transmitted from person to person. That is why it was able to spread so far around the world and cause a pandemic that has been going on for more than a year, while its closest relative, SARS-CoV-1, responsible for the outbreak of SARS in the early 2000s, quickly faded away. Due to a change in part of the genotype, the new coronavirus has significantly increased its transmissivity. This allowed him, on the one hand, to be transmitted to more people, and on the other hand, the extended incubation period of SARS–CoV-2 also played into the hands of the virus. The activity of the virus circulation and indirectly the frequency of mutations are also influenced by the peculiarities of living and the social environment in some area. If people live crowded in a certain area and have a lot of contact with each other, this creates favorable conditions for the spread of the virus. In addition, the source for new varieties of SARS-CoV-2 can be people who, due to the peculiarities of the state of health, the virus gets the opportunity to stay in the body for an abnormally long time.
As a rule, with the usual course of the disease, the chance of the occurrence of many stable mutations in the human body is extremely small. However, people with some chronic diseases, such as primary immunodeficiency, can become a kind of incubators for new varieties of SARS-CoV-2.
Which strains are most common now?
In total, five alarming variants of SARS-CoV-2 have been identified by this time, in which scientists have found significant genome changes mediating changes in the properties of the virus. Researchers primarily pay attention to their transmissivity, lethality and the ability to bypass the immune defense formed by the disease or vaccination.
The most famous due to the wide distribution area was the British version of SARS-CoV-2, also known as B.1.1.7. It was first recorded in December 2020 and later identified in almost all countries of Western Europe and North America, as well as in Japan, Australia and Brazil. The main danger of this variety is its increased transmissibility: according to various estimates, a patient infected with the British version of the virus can infect 50% more people. It is more difficult to assess mortality, but there is evidence that mortality from this type of SARS-CoV-2 could increase by 35%. Fortunately, the effectiveness of vaccines against it is on average the same as against the variants of the virus on the basis of which these vaccines were developed.
Another significant variety of SARS-CoV-2, B.1.429, was first discovered in the USA, California, in June 2020. For a long time it spread locally, but over time it was detected throughout the state, and isolated cases were registered in many countries. In February 2021, scientists discovered a new, hybrid version of the California variant, which has part of the genome of the British variety. By itself, the California version, according to research, was somewhat less vulnerable to antibodies, and now there is a chance of its wider distribution.
The South African variant of SARS-CoV-2, B.1.351, was first identified in October 2020, and the studies were completed by the end of December. Most often this variety was found in the South African countries, as well as in the UK and other Western European countries. The key differences of this strain are high transmissivity, comparable to the British version, and relatively high resistance to antibodies. A number of studies show that the strain evades the immune response better and a higher level of antibodies is required to neutralize it. These data vary from vaccine to vaccine, but in all cases lower efficacy is recorded. Fortunately, there is no data indicating a greater lethality of the South African variant of SARS-CoV-2.
Most of the questions at the moment are caused by the Brazilian version of SARS-CoV-2 under the code name P.1. For the first time it was discovered in In Japan on January 6, 2021, four people returned from the Brazilian Amazon region. The capital of the Manaus region attracted the attention of virologists by the fact that in a short time there were two outbreaks of COVID-19 at once – in May 2020 and at the turn of 2020-2021. During this time, the natural post-infectious immunity could not completely disappear, and this suggests that the Brazilian variety of SARS-CoV-2 has mutations that escape from interaction with protective antibodies.
Preliminary studies of this variant of the virus suggest that it may also be one and a half (according to some sources – two) times more contagious than those that were previously. Moreover, there are concerns that the Brazilian strain may have an increased lethality, although the high number of people killed by this variant of the virus may also be explained by the disproportionate burden on the Manaus health system.
At the same time, it is important to remember that the empirical basis for all these studies was collected in the field, and not within the framework of a controlled experiment. For the first time, humanity finds itself in a situation where data on a pandemic is growing at such a tremendous rate. Under normal conditions, scientists take months and years to summarize such results, so in such an extreme situation, mistakes, inaccuracies and hasty conclusions are certainly possible.
How do different variations of coronavirus affect the body?
At the moment, no serious differences have been identified between the variants of SARS-CoV-2 that can affect its mechanism of interaction with humans.
All its variants still affect primarily the human respiratory system, interacting with alveolar epithelial cells.
However, SARS-CoV-2 variants may differ in the effectiveness of such interaction. Thus, the modified spike protein found in British strains, according to the information available today, can interact more actively with human cells, which may partly explain its higher transmissivity.
Is it possible to get over several varieties of SARS-CoV-2 at once?
Re-infection is even possible with the same type of virus, since the level of antibodies in human blood decreases over time. In the case of new variants of SARS-CoV-2, the risk of getting sick again is higher. This is due to the fact that antibodies are produced against certain proteins present in a particular strain.
If any significant changes occur in it, then some of the antibodies will not be able to help in any way in the fight against the changed SARS-CoV-2. At the same time, the remaining part of the antibodies will not be enough to effectively neutralize the virus and stop the infection.
How effective are existing vaccines to combat new variations of SARS-CoV-2?
The effectiveness of vaccines in medicine is measured by estimating the amount (this indicator is called a titer and is measured in units of antibodies per a certain volume of blood) and the variety of antibodies to the virus in human blood. Based on the data obtained on vaccines against SARS-CoV-2, we have to admit that vaccination is less effective against some varieties. For example, more neutralizing antibodies are required against the South African variant. AstraZeneca and Pfizer/BioNTech vaccines are not enough, because they were developed on the basis of the original version of SARS-CoV-2.
But this is normal and should not cause too much concern. Most vaccines against other infections were developed long ago based on variants of viruses that were common about 30-60 years ago. These vaccines are working fine now, and they are not going to be abandoned in the near future.
Even if the new vaccines do not provide one hundred percent protection against all varieties of SARS-CoV-2, the antibodies produced with their help will still help a person fight the disease. The primary task of medicine is to protect patients from the serious consequences of COVID–19: pneumonia, thrombosis and others. Any vaccine significantly reduces the risk of a severe course of the disease, so you should not refuse vaccination due to the lack of its absolute effectiveness.
About the author: Lyubov Kozlovskaya is a Candidate of Biological Sciences, Head of the Laboratory of Polio and Other Enterovirus Infections with the WHO Reference Center for Polio Surveillance of the M.P. Chumakov FNCRIP of the Russian Academy of Sciences.
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