Coronavirus mutation: SARS-CoV-2 and its variants

Coronavirus mutation: SARS-CoV-2 and its variants

It is not uncommon for viruses to mutate; on the contrary, it is an entirely normal process. But what does that mean for the SARS-CoV-2 coronavirus and the disease it causes, COVID-19? Which mutations have already taken place, and what are the dangers of mutations such as the virus variants alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529)? What are the implications of changing the virus regarding treatment and vaccines? We explain that and more here.

What is a mutation?

Humans, animals, plants, bacteria, fungi and viruses have a genetic code that determines their appearance and properties. This code is the genetic material – the chemical term is deoxyribonucleic acid (DNA) or ribonucleic acid (RNA).

The code is a sequence of chemical structures that work like a blueprint to build the human or virus, allow living things to metabolize, and keep them alive. In the case of humans, this blueprint not only determines that they are human but also how tall they are and what colour their hair, eyes and skin are.

The same applies to the virus. The genetic code dictates:

  • which living beings the virus can infect
  • how it spreads
  • which organs the virus affects
  • in what form it is disease-causing or non-disease-causing
  • everything that makes the virus a virus

This genetic code constantly changes as a virus spreads, which means the chemical structure of the blueprint changes. Not only does this happen in viruses, but humans also have constant changes called mutations.

 

Why do mutations arise?

Mutations are a prerequisite, for there are different living beings that all look different, and living beings are always optimally adapted to their live environment and can survive and reproduce in the best possible way. The changes in DNA occur randomly, for example, when an error occurs in the process of copying the genetic code (during cell division in the body), when chemical substances change the structure or when radiation hits the DNA.

Individuals whose DNA and, thus, their genes are altered can acquire other characteristics. However, a mutation alone is usually not enough to change the properties. Changes in characteristics occur throughout different generations with many mutations.

A virus then gains the opportunity, for example, to enter respiratory tract cells. When this new trait fits better into the current environment of the virus, the altered individual manages to survive longer or reproduce better. In this sense, one speaks of selective advantage. However, the opposite can also occur, and the individual may suffer disadvantages due to the change.

Mutations can, therefore, have a positive or negative effect on an individual. Only when a change in characteristics leads to better adaptation to the environment can the individual reproduce better, and the mutations can thus prevail and be passed on.

Why mutations in viruses are not uncommon

Compared to humans, mutations in viruses are much more common because their DNA or RNA is not as well protected, there are few repair mechanisms, and there is a much faster replication cycle. As a result, mutations occur more frequently and quickly. A virus is, therefore, constantly changing and is continuously being adapted to the new living environment within a very short time.

Viruses change due to this adaptation so that they become specialized for a different host; for example, i.e. they infect humans instead of animals. Another consequence of a mutation could be that the virus infects other organs, causing pharyngitis instead of pneumonia.

 

Mutations in SARS-CoV-2

There are also constant mutations in the genetic code of the SARS-CoV-2 coronavirus. Such a mutation initially made it possible for the virus, which usually infects animals, also to infect humans.

A significant change in the virus can also be seen compared to its relative, the strain SARS-CoV-1. This virus was highly specialized in the lungs and was less found in the throat. This differs from SARS-CoV-2 because it mainly affects the nose and throat in the early stages of infection. Such changes are the result of mutations.

In addition to these two crucial mutations of the coronavirus, science has already discovered numerous other, relatively insignificant mutations – on average, the virus mutates every two weeks. These mutations are constantly taking place and are very instructive for research.

For example, it is possible to use the mutations to carry out a geographic assignment, that is, a family analysis of the virus, and to trace its lineage. For this purpose, the observed virus sequences are documented in a database.

Suppose a person who travels a lot becomes infected with the virus. In that case, one can trace the country in which they were infected based on knowledge of the regionally widespread mutations and the affiliation of the virus. In this way, it was even possible to detect two different populations of the coronavirus in some people. For example, the upper respiratory tract was infected with an additional strain of the virus than the lungs.

Compared to other countries, Germany initially paid less attention to genome sequencing, i.e. the genetic analysis of the virus strain. In January 2021, given various new mutations, it was suggested that a certain proportion of the positive PCR samples should, in future, be subjected to a corresponding analysis to identify new virus variants at an early stage.

Virus variants: central mutations of the coronavirus

The World Health Organization (WHO) distinguishes between different virus variants of concern (VOC) and virus variants under observation (variants of interest, VOI). These variants are named after the letters of the Greek alphabet. The following are currently of concern:

  • Alpha (B.1.1.7)
  • Beta (B.1.351)
  • Gamma (P.1)
  • Delta (B.1.617.2)
  • Omikron (B.1.1.529)

Coronavirus mutation alpha (B.1.1.7) from Great Britain

In December 2020, it was reported that a mutation of the coronavirus was spreading at great speed in the UK and that the spread could not be controlled. This form of the virus with the name Alpha (B.1.1.7)  (initially VUI 202012/01) was originally considered more lethal than the original type. Still, according to current knowledge, this is different. However, the virus variant is significantly more contagious, and infected people have a higher viral load. According to studies, the effectiveness of the vaccines already approved against coronawith this virus is almost as high as that of the previously common virus variant.

It is characteristic of this variant of the virus that it has many mutations in the area of ​​the spike proteins. The virus needs these proteins to dock onto cells in the body and then infect them. This change makes it easier for the virus to multiply and infect people. There is also evidence that Alpha could infect children more efficiently than previous variants of the coronavirus.

Overall, this mutation of the coronavirus contributed to the renewed increase in the number of infections as part of the third wave. In addition to an additional burden on the healthcare system, an increase in infections also means that there are more cases of severe disease and more deaths overall.

 

Beta and Gamma: mutations in South Africa and Brazil

A similar mutation of the virus called Beta (B.1.351 or 501Y.V2)  was also discovered in South Africa. It could be responsible for the rapid spread of the second wave of the coronavirus there. The mutation became known in December 2020. In January 2021, the first cases were also reported in Germany. A form of the virus with a similar mutation (B.1.1.28) has also been observed in Brazil, for which Gamma or P.1 designations are used.

The two mutations have in common that they carry the gene change E484K and could be less sensitive to antibodies. People who have recovered could be infected with the coronavirus a second time. The two virus variants can also impair the effect of the vaccines.

Delta (B.1.617.2) – Mutant from India

The virus variant Delta (B.1.617.2), which first spread primarily in India, was first detected in Germany in March 2021 and classified as alarming by the World Health Organization on May 10, 2021.

The virus variant carries two mutations in a surface protein that could reduce the effectiveness of antibodies or T cells. This, in turn, could mean less protection for those vaccinated or who have already recovered. Similar changes were observed in the South African mutant Beta and the Brazilian variant Gamma.

The delta variant is considered to be more contagious than the alpha variant and is more likely to cause severe courses. Even if those who are fully vaccinated are well protected, this variant poses a risk to those who are unvaccinated or partially vaccinated. In Great Britain, this virus variant caused a renewed increase in the number of infections and soon became the dominant variant in Germany.

In June 2021, India reported a new variant of concern the country: Delta plus (AY.1). This virus variant is even easier to transmit, binds to lung cells more efficiently and is potentially more resistant to monoclonal antibody therapy, which in many cases can be used to lower the viral load. The variant AY.4.2, first detected in Great Britain, is also called Delta Plus.

Omikron: B.1.1.529 als “Variant of Concern”

At the end of November 2021, the WHO classified the virus mutant B.1.1.529, named Omicron, as a concern. The virus variant was first detected in southern Africa. In contrast to the wild type, it shows an unusual number of changes, including the spike protein.

The variant is considered more contagious. It is still being investigated whether it is also more dangerous regarding severe courses. There is evidence that infections with the omicron variant may be less stringent than with the delta variant. Nevertheless, experts warn against underestimating the virus variant and expect an enormous increase in infections.

 

Other virus variants

In addition to the worrying variants mentioned, there are numerous other mutations, some of which are presented in more detail below.

B.1.640.2 – new Corona variant discovered in France

In December 2021, a new virus variant became known in southern France and received the classification B.1.640.2. Its origin is assumed to be in Cameroon since the patient who was presumably the first to be infected had previously returned from a trip to Cameroon.

The virus variant has some mutations in the spike protein. It is assigned to the B.1.640 variant family, which was first discovered in the Democratic Republic of the Congo and has been observed by the WHO for some time. However, it spread little there. Regarding B.1.640.2, experts see no cause for concern since no rapid spread has been observed. In addition, too little is known about the virus variant to be able to say more precisely. The variant should, therefore, initially be monitored further.

From South America: B.1.621

The Mu variant (also My variant) has largely displaced the other virus variants, especially in Colombia, after its first discovery in January 2021. The World Health Organization, therefore, added it to the list of virus variants under surveillance in September 2021.

The variant has also been found in numerous other countries, but its distribution is mainly regionally limited. The virus variant is more resistant than the original type: both the vaccination and the antibodies of those who have recovered achieved lesser effects in studies.

 

Lambda (C.37): Virus-Mutant from Peru

The lambda variant was first discovered in Peru. Its spread has been limited mainly to South America, although isolated cases have already been found in Europe. Experts estimate the threat from this variant to be lower than the Delta variant: it is more contagious than the original type but not as infectious as Delta. The variant was not classified as a concern by the World Health Organization but as a variant under observation.

C.1.2. – Virus variant with 59 mutations

The virus variant C.1.2. was first discovered in May 2021 in South Africa and is spreading there more and more. Cases have also been recorded in Europe. The variant concerns local experts because it has 59 mutations that, when combined, could impair the immune response. According to current knowledge, C.1.2 spreads similarly to the Beta and Delta variants.

Whether the virus variant could make vaccination less effective or whether it is more contagious is currently unknown and is still being researched. So far, only one previously published study on this virus variant has yet to be reviewed by experts. The World Health Organization has not yet classified the virus variant as alarming, as this only happens if there is reliable evidence of the danger of a virus variant. C.1.2 is currently considered a “variant under monitoring” (VUM).

What mutations of the coronavirus may occur in the future?

For the further development of the coronavirus pandemic, it is difficult to predict in which direction the virus will change due to the randomness of mutations. From a biological point of view, the virus will likely be further adapted to humans. This could make the virus more dangerous, but a development that makes the coronavirus more harmless is also conceivable.

 

Scenarios for dangerous forms of the virus

For example, SARS-CoV-2 could evolve so that the virus can enter other body parts, causing it to end up in different organ systems than it currently does. In addition, other mechanisms could develop to overcome human protective barriers. Infections could then be triggered even faster and more frequently. In addition, factors could arise that protect the virus more extensively from the immune system by changing the points of attack or developing mechanisms to inactivate the immune system to a certain extent. Then, severe pneumonia could be triggered even more frequently, and the virus spread even faster and more extensively than at the moment.

It is currently believed that the virus primarily affects the nose and throat during the first episode of infection and then moves on to the lungs. If it now specializes in these types of organs and is allowed to multiply even faster, then even more inflammation would likely result.

Scenarios for harmless courses

However, there is also the scenario that serious illnesses will become rarer because a virus ensures its survival by infecting many people and spreading widely. It is, therefore, not conducive to the survival of the virus if a person becomes seriously ill and dies since it is no longer possible to spread. The virus can no longer continue to exist in its host.

It can, therefore, be assumed that SARS-CoV-2 will adapt to humans so that it will soon behave like a cold virus, and severe infections will become less common. For example, it could adjust to the olfactory mucosa so that lung infections occur less frequently. Milder symptoms, such as a runny nose, would develop more regularly, resulting in a greater spread of the virus as people stayed homeless, were less aware of the disease and spread the virus unnoticed.

What are the consequences of mutations in drugs and vaccines?

Regarding vaccines that have already developed and are still under development, mutations could become problematic if the areas of the virus are modified by the vaccine and the immune response triggered by it mutates. This could affect the effectiveness of the vaccines, which have already been observed with some virus variants.

In addition, the pressure exerted on the virus by vaccination or even drugs could mean that only those viruses that are immune to these drugs survive and multiply. Such resistances can also be observed in other pathogens against which certain antibiotics are no longer effective.

In addition, mutations can also lead to the virus protecting itself from the human immune system, i.e. the very properties of the virus that the immune system recognizes and attacks change. Thus, the immunity that a person acquires after surviving a viral infection would not exist. A similar effect can be observed with the flu virus, which changes so much yearly that the corresponding vaccine must be adapted for each flu season.

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