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Coronavirus: mutations

by Josephine Andrews
Published: Last Updated on 336 views

The proportion of the omicron variant of Sars-CoV-2 in new infections is currently skyrocketing across Europe. Omicron seems to be significantly more contagious than Delta. Here you can find out what properties the different coronavirus mutations have, where they spread and which virus variants no longer pose a risk.

Mutations are normal

The emergence of new virus variants is nothing unusual: Viruses – including the Sars-CoV-2 pathogen – repeatedly change their genetic material randomly during replication. Most such mutations are meaningless. But some are beneficial for the virus and prevail.

In this way, viruses are able to quickly adapt to the environment and their host. This is part of their evolutionary strategy.

In the meantime, however, so-called “Variants of Concern” (VoC) have appeared with Sars-CoV-2 – ie variants that cause concern for experts. What they have in common is that they are more contagious than the original form of Sars-CoV-2.

According to the current assessment of the European disease control agency ECDC, these are the following variants:

  • Delta: The lineage, also known as B.1.617.2, spread from India.
  • Omicron : The lineage, also called B.1.1.529, spread out from the southern areas of Africa.

Virus variations are grouped into so-called clades or lineages – researchers thus clearly record and document the “family tree of the coronavirus”. Each variant is characterized according to its genetic properties and provided with a combination of letters and numbers. Whether a certain strain of virus is more dangerous than another cannot be determined from this designation.

How is the coronavirus changing?

There are two ways for the coronavirus to develop “successfully”: it changes in such a way that it can get into the human cell more easily, making it more contagious, or it tries to “escape” our immune system by adapting:

Improved cell entry: This is particularly the case when advantageous changes (for the virus) develop within the so-called receptor-binding domain (RBD) of the spike protein: the spike protein is the “door opener” for human cells. The stronger the interaction with the ACE2 receptor of the human cell, the easier it is for a virus particle to get inside the cell – and the more contagious and dangerous the respective virus variant is.

Escape mutation: These are changes that allow the coronavirus to “escape” the immune system. The virus then changes its external shape in such a way that the (already formed) antibodies of an initial infection or vaccination are now less able to “recognize” and neutralize it. One also speaks of “escape mutations” or “immune escape”. This could make secondary infections more likely.

How do the virus variants arise?

The longer the pandemic lasts, the more infections, the more variations and mutations of the coronavirus.

The corona pandemic has been going on for a good two years now: as of January 5, 2022, the Johns Hopkins Coronavirus Resource Center (CRC) reported around 296 million cases of infection worldwide.

Opportunity enough for the coronavirus to accumulate diverse changes (variations) in the genome.

Since not every country on earth can offer comprehensive medical care or has the same testing and documentation capacities as established industrialized countries, one can assume a (very) high number of unreported cases worldwide.

This enormous number of cases – and the associated genetic changes of Sars-CoV-2 – are reflected in the now extensive distribution of a large number of new virus variants:

Delta: The B.1.617.2 line

The delta variant (B.1.617.2) of Sars-CoV-2 has also spread rapidly in Germany in recent months (autumn 2021). It was first discovered in India and is divided into three sub-variants that combine several characteristic changes.

On the one hand, these are changes in the spike protein, which is considered the “key” for the human cell. On the other hand, B.1.617 also shows changes that are discussed as (possible) escape mutations.

Specifically, B.1.617 combines the following relevant mutations, among others:

Mutation D614G: It can make the coronavirus more contagious. Initial modeling indicates that B.1.617 is thereby transmitted at least as easily as the very contagious alpha variant (B.1.1.7).

Mutation T478K: It leads to an exchange of the uncharged amino acid threonine bylysine , which is protonated under physiological conditions – and thus positively charged – at position 478. It is assumed that this amino acid exchange influences the interaction with the ACE2 receptor. Experts suspect that this could trigger more severe Covid 19 diseases.

Mutation P681R: Researchers have also linked this to a potentially increased virulence.

Mutation E484K: Also found in the beta variant (B.1.351) and the gamma variant (P.1). It is suspected of making the virus less sensitive to neutralizing antibodies that have already formed.

Mutation L452R: It is also discussed as a possible escape mutation. In laboratory experiments, some strains of coronavirus with the L452R mutation were resistant to certain antibodies.

The delta variant, which has been so far predominant in Europe, also seems to be being superseded by the highly contagious omicron variant.

Omicron: The B.1.1.529 line

The omicron variant is the latest coronavirus mutation, first detected in Botswana in November 2021. The World Health Organization (WHO) now officially classifies it as a new “Variant-of-Concern”.

Experts are concerned about the high rate of spread. Preliminary genetic analyzes show that the omicron variant has a large number of changes in the spike protein – a good 30 different point mutations in total (compared to the Sars-CoV-2 wild type). All current developments and findings can be found in our separate article on the Omicron variant .

Other known virus variants

In addition, additional Sars-CoV-2 virus variants developed that differ from the wild type – but experts do not yet count them among the VOCs. These virus strains are accordingly referred to as “variants of interest” (VOI) – ie variants of special interest.

It is not yet clear what impact these emerging VOIs could have on the pandemic. Should they assert themselves and prevail against virus strains that are already circulating, they too could be upgraded to corresponding VOCs.

Variants of particular interest

According to the European Center for Disease Prevention and Control (ECDC), these VOI currently include:

  • BA.4: Omicron subtype, first discovered in South Africa.
  • BA.5: Omicron subtype, first discovered in South Africa.

Variants under observation

The so-called “variants under monitoring” (VUM) are in the extended focus – however, there is still a lack of reliable, systematic data on these. In most cases, only proof of their mere existence is available. They include sporadically occurring variants as well as “modified” descendants of known mutations.

According to the ECDC, these rare VUM currently include:

  • XD – Variant first detected in France.
  • BA.3 – Subtype of the omicron variant first discovered in South Africa.
  • BA.2 + L245X – Omicron variant subtype of unknown origin.

Downgraded virus variants

As dynamically as the infection process in the current corona pandemic is developing, so is the scientific knowledge and assessment of the virus variants predominant in the different phases of the pandemic.

It is therefore not surprising that some variants are newly appearing – but others are gradually disappearing again and are therefore no longer considered to be of concern according to expert opinion. The European disease control authority is therefore giving the all-clear for the following coronavirus variants:

Alpha: The B.1.1.7 line

According to official bodies, the coronavirus variant Alpha (B.1.1.7) is hardly circulating in Europe anymore. Alpha was first detected in Great Britain and has been spreading increasingly across the European continent since autumn 2020, starting from south-east England.

With 17 mutations, the B 1.1.7 line had a conspicuously large number of gene changes. Several of these mutations affected the spike protein – the N501Y mutation, among others, being very important.

It is assumed that B.1.1.7 was around 35 percent more contagious than the wild type of Sars-CoV-2. The observed mortality rate from infection (without prior vaccination) was also increased. However, available vaccines provided solid protection.

According to official bodies (ECDC, CDC and WHO), alpha is declining sharply.

Beta: The B.1.351 line

The B.1.351 lineage (501Y.V2) – also called beta according to WHO nomenclature – first spread in South Africa. In addition to N501Y, there are other mutations (E484K, K417N) of the spike protein.

The mutant most likely developed as a result of a high rate of infection of the South African population with the virus. South Africa already recorded large-scale corona outbreaks in the summer months of 2020. In the townships in particular, the virus probably found ideal conditions for rapid spread.

This means that a lot of people were already immune to the original form of Sars-CoV-2 – the virus had to change. Researchers refer to such a situation as evolutionary pressure. Therefore, a new virus variant has prevailed, which was superior to the original form because, among other things, it is more contagious.

The additional mutation E484K is considered by experts to be a possible escape mutation: ie an “escape adaptation” of the corona virus to the human immune system. This could mean that antibodies that the immune system developed against the original form of Sars-CoV- 2 could no longer fully recognize B.1.351. Those affected could therefore become infected a second time.

Preliminary data indicate that the Comirnaty vaccine also has high efficacy against the B.1351 line. On the other hand, according to a preliminary statement by the authors Madhi et al. have reduced effectiveness.

According to official bodies (ECDC, CDC and WHO), beta is declining sharply.

Gamma: The P.1 line

Another VOC called P.1 — previously known as B., now called Gamma — was first detected in Brazil in December 2020. P.1 also has the important N501Y mutation in its genome. The P.1 virus strain is therefore considered to be highly contagious.

Gamma originally developed and spread in the Amazon region. The spread of the variant coincides with the spike in Covid-19-related hospitalizations in this region in mid-December 2020.

The virus was also able to multiply ideally in Brazil for a long time. This resulted in a high degree of infestation among the population. As in South Africa, this could have been the reason for the correspondingly high pressure to adapt to the virus. Here, too, the virus had to “compete” against the human immune system over a longer period of time. A unique combination of specific mutations favorable to the virus has thus prevailed.

Gamma is in sharp decline, according to ECDC, CDC and WHO experts.

More de-escalated variants

Although many new virus variants have become known in the meantime, this does not automatically mean a greater threat. The influence of such variants on the (global) infection process was small, or they were suppressed. These also include:

  • Epsilon: B.1.427 and B.1.429 – first discovered in California.
  • Eta: Proven in many countries (B.1.525).
  • Theta: Previously designated P.3, now downgraded, first discovered in the Philippines.
  • Kappa: First discovered in India (B.1.617.1).
  • Lambda: First discovered in Peru in December 2020 (C.37)
  • Mu: Discovered destroyed in Colombia in January 2021 (B.1.621).
  • Iota: First discovered in the United States in the New York area (B.1.526).
  • Zeta: Previously designated P.2, now downgraded, first discovered in Brazil.

As well as a large number of other variants of different origins: B.1.620, A.27, A.28, C.16, B.1.616, B.1.351+E516Q, B.1.351+P384L, B.1.1.7 +L452R, B.1.1.7+S494P, B.1.526.1, B.1.526.2, B.1.1.519, AT.1, B.1.214.2, AY.4.2 – and many more.

How fast does Sars-CoV-2 mutate?

In the future, too, Sars-CoV-2 will continue to adapt to the human immune system and a (partially) vaccinated population through mutations. How quickly this happens depends largely on the size of the actively infected population.

The more cases of infection – regional, national and international – occur, the more the coronavirus multiplies – and the more frequently mutations occur.

However, the coronavirus mutates relatively slowly compared to other viruses. With a total length of the Sars-CoV-2 genome of around 30,000 base pairs, experts assume one to two mutations per month. For comparison: Flu viruses (influenza) mutate two to four times as often in the same period.

How can I protect myself from coronavirus mutations?

You cannot protect yourself against individual coronavirus mutations themselves – the only possibility is not to become infected.

In general, follow hygiene rules, keep your distance and wear your FFP2 mask in public. If you get vaccinated, you will also enjoy good basic immunity against severe courses.

How are coronavirus mutations detected?

Germany has a close-meshed reporting system to monitor circulating Sars-CoV-2 viruses – it’s called an “integrated molecular surveillance system”. The relevant health authorities, the Robert Koch Institute (RKI) and specialized diagnostic laboratories work closely together.

How does the reporting system work if mutations are suspected?

First of all, every positive coronavirus test carried out professionally must be reported to the responsible health authority. This includes coronavirus tests carried out in a test center, at your doctor’s, in your pharmacy or at government institutions such as schools. However, private self-tests are excluded from this.

Further information on rapid coronavirus tests for self-use can be found in our special topic on corona self-tests .

If the result is positive, doctors send the corresponding patient sample to a specialized diagnostics laboratory, which confirms the result using a PCR test . If the PCR test is also positive, the sample can also be sent to a sequencing laboratory for further examination there (sequencing genome analysis).

The RKI then compares the reporting data and the result of the sequence analysis in pseudonymised form. Pseudonymised means that it is not possible to draw conclusions about an individual person. However, this information forms the data basis for scientists and healthcare professionals to get an accurate overview of the existing pandemic situation. This enables the best possible assessment of the situation in order to (if necessary) derive political measures.

What is sequencing genome analysis?

A sequencing genome analysis is a detailed genetic analysis. She examines the exact sequence of the individual RNA building blocks within the viral genome. This means that the Sars-CoV-2 genome, which has around 30,000 base pairs, is decoded and can then be compared with that of the wild type coronavirus.

Only in this way can the individual mutations be recognized at the molecular level – and an assignment within the “coronavirus family tree” possible.

Genome sequencing is a time-consuming and costly process with (very) limited capacities. Not every positive sample can therefore be routinely sequenced. Experts make a pre-selection – they collect a sample.

This also makes it clear that not every country in the world is able to track the exact spread of certain coronavirus variants in detail. A certain degree of imprecision in the available reporting data is therefore likely.

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