Mutations are normal
The emergence of new viral variants is nothing unusual: viruses – including the Sars-CoV-2 pathogen – repeatedly change their genetic material at random during replication. Most of these mutations are meaningless. Some, however, are advantageous for the virus and become established.
In this way, viruses are able to adapt quickly to the environment and their host. This is part of their evolutionary strategy.
The WHO classifies new variants according to the following categories:
- Variants under monitoring (VBM) – Variants with genetic changes that could mean a higher risk, but with effects that are still unclear.
- Variant of interest (VOI): Variants that have genetic features that are predictive of higher transmissibility, bypassing immunity or diagnostic tests, or more severe disease compared to previous forms.
- Variant of high consequence (VOHC) – Variant with high consequence: Variant against which current vaccines offer no protection. To date, there have been no SARS-CoV-2 variants in this category.
Virus variations are grouped into so-called clades or lineages – researchers thus systematically record and document the “family tree of the coronavirus”. Each variant is characterized according to its hereditary properties and assigned a letter-number combination. However, this designation does not indicate whether a particular strain of the virus is more dangerous than another.
How does the coronavirus change?
There are two ways for the coronavirus to “successfully” evolve: It changes in such a way that it can better enter the human cell, thus becoming more infectious, or it tries to “escape” our immune system by adapting:
Escape mutation: These are changes that enable the coronavirus to “escape” from the immune system. The virus then changes its external shape in such a way that the antibodies (already formed) of an initial infection or vaccination are now less able to “recognize” and neutralize it. This is also referred to as “escape mutations” or “immune escape”. Second infections could thus become more likely.
How do the virus variants develop?
The longer the pandemic lasts, the more infections, the more variations and mutations of the coronavirus.
The Corona pandemic has now been ongoing for a good two years: As of January 05, 2022, the Johns Hopkins Coronavirus Resource Center (CRC) now reports about 296 million cases of infection worldwide.
Opportunity enough for the coronavirus to accumulate multiple changes (variations) in the genetic material.
These enormous numbers of cases – and the accompanying genetic changes in Sars-CoV-2 – are reflected in the now extensive spread of a large number of new virus variants:
Delta: The B.1.617.2 lineage
The delta variant (B.1.617.2) of Sars-CoV-2 also spread rapidly in Germany in recent months (fall 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 exhibits changes that are discussed as a (possible) escape mutation.
Specifically, B.1.617 combines the following relevant mutations, among others:
Mutation D614G: It can make the coronavirus more contagious. Initial modeling suggests that this makes B.1.617 at least as easily transmitted as the highly contagious alpha variant (B.1.1.7).
Mutation P681R: Also associated by researchers with possibly increased virulence.
Mutation E484K: Has also been found in the beta variant (B.1.351) and the gamma variant (P.1). It is suspected to make the virus less sensitive to neutralizing antibodies already formed.
Mutation L452R: It is also discussed as a possible escape mutation. Coronavirus strains with the L452R mutation were partially resistant to certain antibodies in laboratory experiments.
The delta variant, which has been predominant in Europe up to now, also seems to be displaced in large steps by the highly contagious omicron variant.
Omikron: The B.1.1.529 lineage
The Omikron variant is the most recent coronavirus mutation, first discovered in Botswana in November 2021. It is now officially classified as a novel variant-of-concern by the World Health Organization (WHO).
Eris: The EG.5 lineage
The EG.5 variant of coronavirus is from the Omikron lineage. It was first detected in February 2023. Since then, it has been spreading in various countries around the world and dominating the infection scene in many places. It is also called Eris, after the Greek goddess of discord and strife.
EG.5 descends from the omicron variants XBB.1.9.2. and XBB.1.5, but also has a novel mutation in the spike protein (F456L). The EG.5.1 subline also carries yet another Q52H mutation.
Is EG.5 more dangerous than the previous variants?
With the emergence of EG.5, the number of cases of corona infection is rising again, and with it, hospitalizations. So far, no changes in the severity of the disease have been reported, according to WHO. WHO has therefore classified EG.5 as a variant of interest (VOI), but not a variant of concern (VOC).
The matched booster vaccines for the fall are not precisely targeted to EG.5, but to a closely related viral lineage (XBB.1.5 ). Early clinical studies indicate that booster vaccination is also effective against EG.5.
Pirola: The BA.2.86 lineage
The BA.2.86 virus variant is also an omicron derivative. It differs from its putative predecessor variant BA.2 by 34 new mutations in the spike protein, making it similarly divergent from earlier forms as Omicron was most recently.
How common is BA.2.86?
So far, the variant has been found in only a few people. However, little testing is now done overall. In particular, elaborate tests that determine the particular viral variant are rare. The fact that the known cases come from three continents (North America, Asia and Europe) and are not directly related suggests that Pirola has already spread unnoticed.
Is BA.2.86 more dangerous than the previous variants?
Are the adapted vaccines effective against BA.2.86?
The vaccines available from September are optimized for the XBB.1.5 variant. Its spike protein differs from that of Pirola in 36 sections. Protection against infection is therefore likely to be reduced. However, experts believe that protection against severe courses still remains.
Other known virus variants
Additional Sars-CoV-2 virus variants have also developed that differ from the wild type – but experts do not currently classify them as VOCs. These virus strains are referred to as “Variants of Interest” (VOI).
It is not yet clear what impact these emerging VOIs might have on the pandemic. Should they assert and prevail against already circulating virus strains, they too could be upgraded to corresponding VOCs.
Variants of particular interest
- BA.4: Omicron subtype, first discovered in South Africa.
- BA.5: Omicron subtype, first discovered in South Africa.
Variants under monitoring
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 evidence of their mere existence is available. They include sporadically occurring variants as well as “modified” descendants of already known mutations.
According to the ECDC, these rare VUMs currently include:
- XD – variant first detected in France.
- BA.3 – subtype of the Omikron variant, first detected in South Africa.
- BA.2 + L245X – subtype of the omicron variant of unknown origin.
Downgraded virus variants
As dynamically as the infection events in the ongoing Corona pandemic are evolving, so too is the scientific understanding and assessment of the virus variants prevalent in different phases of the pandemic.
Alpha: The B.1.1.7 lineage
Coronavirus variant Alpha (B.1.1.7) is barely circulating in Europe anymore, according to officials. Alpha was first detected in the United Kingdom and, starting in southeastern England, has been increasingly spreading across the European continent since the fall of 2020.
The B 1.1.7 lineage had a strikingly high number of gene alterations, with 17 mutations. Several of these mutations affected the spike protein – very significantly including the N501Y mutation.
B.1.1.7 is thought to have been about 35 percent more contagious than wild-type Sars-CoV-2, and the observed mortality rate from infection (without prior vaccination) was also increased. However, available vaccines conferred robust protection.
Alpha is strongly declining in agreement with official agencies (ECDC, CDC as well as WHO).
Beta: The B.1.351 lineage
The mutant most likely developed as a result of a high infestation 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 to spread by leaps and bounds.
This means that very many 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. As a result, a new virus variant prevailed that was superior to the original form because, among other things, it is more contagious.
Preliminary data suggest that the Comirnaty vaccine also has high efficacy against the B.1351 lineage. VaxZevria, on the other hand, may have reduced efficacy, according to a preliminary statement by authors Madhi et al.
Beta is in strong decline in agreement with official agencies (ECDC, CDC as well as WHO).
Gamma: The P.1 line
Another VOC called P.1 – previously known as B.1.1.28.1, now called Gamma – was first discovered in Brazil in December 2020. P.1 also has the important N501Y mutation in its genome. Thus, the P.1 virus strain is considered highly contagious.
Gamma originally evolved and spread in the Amazon region. The spread of the variant coincides with the surge in Covid-19-related hospitalizations in this region in mid-December 2020.
Gamma is declining sharply in agreement with experts from ECDC, CDC, and WHO.
Further de-escalated variants
Although a large number of novel virus variants have now become known, this did not automatically mean a greater threat. The influence of such variants on the (global) infection incidence was small, or they were suppressed. These include:
- Epsilon: B.1.427 as well as B.1.429 – first discovered in California.
- Eta: Detected in many countries (B.1.525).
- Theta: Previously designated P.3, now downgraded, first discovered in the Philippines.
- Kappa: First detected in India (B.1.617.1).
- Lambda: First discovered in Peru in December 2020 (C.37).
- Mu: First discovered in Colombia in January 2021 (B.1.621).
- Iota: First discovered in the USA in the New York metropolitan area (B.1.526).
- Zeta: Previously designated P.2, now downgraded, first discovered in Brazil.
How quickly does Sars-CoV-2 mutate?
In the future, Sars-CoV-2 will continue to adapt to the human immune system and to 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 there are – regionally, nationally and internationally – the more the coronavirus multiplies – and the more frequently mutations occur.
Compared to other viruses, however, the coronavirus mutates relatively slowly. With a total length of the Sars-CoV-2 genome of about 30,000 base pairs, experts assume one to two mutations per month. By comparison, flu viruses (influenza) mutate two to four times as frequently in the same period.
How can I protect myself from coronavirus mutations?
You cannot specifically protect yourself from individual coronavirus mutations – the only possibility is not to become infected.
How are coronavirus mutations detected?
Germany has a close-meshed reporting system to monitor circulating Sars-CoV-2 viruses – it is called “integrated molecular surveillance system”. To this end, the relevant health authorities, the Robert Koch Institute (RKI) and specialized diagnostic laboratories work closely together.
How does the reporting system work in the case of suspected mutations?
First of all, every professionally performed positive coronavirus test is subject to mandatory reporting to the relevant public health department. This includes coronavirus tests performed at a testing center, at your doctor’s office, at your pharmacy, or even at government facilities – such as schools. However, private self-tests are excluded from this.
For more information on rapid coronavirus tests for self-testing, see our Corona self-testing topic special.
The RKI then compares the reported data and the result of the sequence analysis in pseudonymized form. Pseudonymized means that it is not possible to draw conclusions about an individual person. However, this information forms the data basis for scientists and actors in the health care system to obtain an accurate overview of the existing pandemic situation. This enables the best possible assessment of the situation in order to derive policy measures (if necessary).
What is a sequencing genome analysis?
A sequencing genome analysis is a detailed genetic analysis. It examines the exact sequence of the individual RNA building blocks within the viral genome. This means that the Sars-CoV-2 genome, which comprises 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 identified at the molecular level – and an assignment within the “coronavirus family tree” is possible.
This also makes it clear that not every country in the world is able to track the exact spread of specific coronavirus variants in detail. Some uncertainty in the available reporting data is therefore likely.
