How dangerous is Omicron? – What we know so far about the new coronavirus variant and its mutations –

Mutated pathogen: The new Coronavirus variant Omikron is spreading, it has also been detected several times in Germany. With 50 mutations, 30 of which are in the spike protein, it is the most strongly mutated form of SARS-CoV-2 to date. It combines some mutations already known from other variants with many whose effects are still completely unknown. It is therefore not yet clear how well the vaccines protect and how much more contagious it is.

It was to be expected: like most viruses, the SARS-CoV-2 coronavirus continues to adapt to its hosts – it mutates. Many of these changes in its RNA are useless or even harmful, but there are always some mutations that benefit the virus and that therefore spread. About a year ago, the alpha variant was created, which spreads from Great Britain across Europe, followed a little later by the even more contagious delta variant, which now dominates in most regions.

Where does Omicron come from?

Now the next worrying variant of SARS-CoV-2 has emerged. The variant B.1.1.529, now called “Omikron”, was first detected on November 9th in the Gauteng Province in South Africa. Within a week, the proportion of this mutant rose from one to seven percent, at the same time as there was a sharp increase in Covid 19 cases. So far, in South Africa, as with us, the delta variant has dominated.

The rapid increase in the Omikron variant suggests that it can prevail over Delta. This is one of the reasons why the World Health Organization (WHO) officially declared it a “Variant of Concern” (VOC) on November 26th. Another reason: “Omicron is the most strongly mutated form of this virus of all known variants,” says Lawrence Young, virologist at the University of Warwick. “This variant of SARS-CoV-2 is very worrying.”

Preliminary mapping of the omicron (B.1.1.529) mutations on the spike protein. © Coronavirus Antiviral & Resistance Database/ Stanford University,CC-by-sa 4.0

New combination of mutations

In total, the omicron variant carries changes in its RNA in 50 places – more than any other. 30 of these mutations affect the spike protein, of which around 15 are in the receptor binding domain, the protein segment with which the coronavirus docks to the ACE2 receptor of our cells. This domain plays a crucial role in how well the virus can infect.

Some of these mutations are already known from other virus variants. “Omikron carries some changes that we have seen before in other variants, but never all together in one virus,” says Young. These include six mutations that the alpha variant already has and three that the delta variant has developed.

Among these changes are three mutations in what is known as the furin cleft of the spike protein. One of these mutations, an amino acid swap at position 681 of the protein, is already known to increase the transferability. A combination of two other mutations, Q498R and N501Y, strengthens the binding of the virus to the cells and thereby also increases the infectivity.

Evidence of higher infectivity

Taken together, Omikron carries a number of mutations that are known to increase transmissibility and viral load. This fits in with the assumption derived from the epidemiological data that this new variant could be even more contagious than Delta. There were also initial reports from Hong Kong that the viral load of two people infected with the Omicron variant was significantly higher than normal.

Whether the transferability of the variants is actually significantly higher and by how much higher the R value of the Omikron variants is, however, must first be clarified through laboratory tests. Because even if this form of coronavirus carries many of the known more infectious changes, among the previously unseen mutations in its genome there may be some that weaken this effect again. “The meaning of many of these new mutations and their combinations is still unknown,” emphasizes Sharon Peacock from the British Genome Consortium and the University of Cambridge.

Potential escape mutations

So far there are no clear data on whether and to what extent the Omikron variant can evade the immune system, which has been armed with vaccinations or previous infections. Both Moderna and BioNTech are already in the process of checking the effectiveness of their vaccines against this variant in cell culture tests. “The combination of the mutations represents a significant risk that this variant can accelerate the decline in the natural immunity indicated by vaccination,” says Moderna.

This assumption is based on several mutations that have long been considered potential escape mutations. They change important identifying features on the spike protein to such an extent that some antibodies formed against SARS-CoV-2 no longer recognize the virus. Specifically, this includes a mutation at position E484, which already occurred in a similar form in the gamma variant widespread in Brazil and the beta variant previously circulated in South Africa.

In addition, the omicron variant carries three amino acid deletions in the ORF-1a section of the viral RNA, which also make it difficult for the immune system to attack the virus.

How well do the vaccinations protect?

But what does this mean for vaccination protection? Most experts believe that there is still no reason to panic. “It is very likely that the current vaccines will also protect Omikron against severe courses of Covid-19,” says Young. The virologist Peter Openshaw from Imperial College London sees it similarly: “It is extremely unlikely that this variant can completely elude the vaccine effect.”

One of the reasons: Because the vaccines use all of the spike protein as the basis for the immune response, the body produces antibodies that attach to different parts of the viral protein. Even if some attachment sites are now mutated, there are still antibodies that attach to the unchanged sites of the spike protein.

The same applies to the second pillar of immune protection, the cells: “The T cell response in particular should be robust to the changes. However, it is quite conceivable that there will be more breakthrough infections, so that a third dose will be all the more important, ”says Roman Wölfel from the Bundeswehr Institute for Microbiology in Munich. Other virologists also emphasize that a fresh vaccination protection and thus a booster vaccination is now all the more important.

Quelle: Covariants, GISAID, WHO, Science Media Centre

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