Is the Omicron BA.2 variant really more infectious and destructive?

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BA2 is indeed likely to become the mainstream mutant strain and the main virus strain of the Hong Kong epidemic, but it is unlikely to change the overall epidemic situation from a global perspective

BA.2 mutants have been found in more than 40 countries around the world, and the proportion of BA.2 in all genome sequencing is also rising, showing that BA.2 has the potential to become a mainstream mutant in different countries and regions.
In terms of propagation speed, BA.2 is indeed faster than BA.1. However, whether BA.2 is more pathogenic, based on real-world tracking, has not seen a significant difference between the two.
At present, BA.2 may not trigger a new wave of global epidemics. However, due to the stronger contagion, the emergence of BA.2 may slow down the rate of decline in this wave of Omicron cases, and we must remain vigilant about BA.2.

At a time when the number of new cases in Omicron is starting to decline globally, another mutant strain is starting to attract attention – Omicron’s offshoot BA.2. There have also been recent reports of BA.2 spreading faster or causing more severe disease. So, what impact will BA.2 have on the epidemic?

1. Has the potential to occupy the mainstream

BA.2 is getting a lot of attention now because it has been discovered in more than 40 countries around the world, which can be said to have international influence.

In addition, the proportion of BA.2 is on the rise in all genome sequencing, which means that it seems to have a competitive advantage over other mutants and is leaning in the direction of mainstream mutants.

As of February 14, in the proportion of sequences submitted to the new coronavirus genome sequencing database GISAID, BA.2 accounted for the majority (>50%) of new cases in 10 countries [1], including several Asian Countries such as China, India, the Philippines. Now the epidemic situation in Hong Kong is mainly BA.2.

The whole genome sequence of the virus submitted to the COVID-19 genome sequence library is affected by the sequencing capacity and sampling number of different countries, and may not accurately reflect the actual prevalence of mutant strains.

If looking at the individual countries’ own tracking, in South Africa, the proportion of BA.2 increased from 27% on February 4 to 86% on February 11. Denmark will rise from 20% at the end of 2021 to 45% in early January 2022 [1].

It should be noted that among the countries where the proportion of BA.2 has increased, there are both countries where the Omicron peak has passed and the overall number of cases has declined, and there are also areas where the Omicron outbreak has just broken out.

This shows that this substrain has become mainstream in different countries and regions. Potential of mutant strains.

2. The speed of spread is faster

The mainstream mutant strain in the world today is Omicron’s BA.1, so the characteristics of BA.2 are generally compared with BA.1.

A very clear feature now is that the spread of BA.2 is faster than that of BA.1, which is why the proportion of BA.2 in many countries is rising and even occupying the mainstream.

For example, Denmark compared the local growth rate of BA.1 and BA.2, and found that the spread of BA.2 was 30% higher than that of BA.1 [2].

The United Kingdom and Denmark have also compared the secondary attack rate of BA.2 and BA.1 in the family, and both found that the risk of further transmission of BA.2 in the family is higher, such as the British study showed The second-generation incidence of BA.2 in families is 13.4%, while that of BA.1 is 10.3% [1].

Why does BA.2 spread faster than BA.1? This aspect still needs further research. In terms of specific mutations, BA.2 and BA.1 have many differences (see the figure below) [3]:

Is the Omicron BA.2 variant really more infectious and destructive?

Figure: Schematic diagram of the overlap of mutation sites in each variant of Omicron

Humans can mount an immune response to both mutants, and a Danish comparison of family transmission of the two mutants found that BA.2 also spreads faster than BA.1 in unvaccinated people, these preliminary findings.

Research is pointing to the fact that BA.2 is more self-transmissible than BA.1, rather than more serious immune escape [1].

3. Pathogenicity may not be more serious

Could BA.2, which spreads faster than BA.1, cause more severe disease? A recent study in Japan has attracted a lot of attention.

This study shows that the disease severity of hamsters infected with BA.2 is greater than that of BA.1, that is, BA.2 may be more pathogenic than BA.1 [4].

This study has caused some panic, but this is only a preliminary study. In the real world, BA.2 and BA.1 showed no difference in pathogenicity from tracking in the United Kingdom, Denmark and South Africa. 【1】.

For example, in a study in South Africa, researchers analyzed 95,000 COVID-19-positive infections and found that 3.6% of people with BA.2 infections required hospitalization, and BA.1 was 3.4%, no significant difference [5].

However, it should be noted that the United Kingdom, South Africa and Denmark are all countries with a relatively high basis for COVID-19 immunity.

The United Kingdom and Denmark have very high vaccination rates. South Africa has a lot of natural infections in the past, and the population structure is also younger.

Therefore, these countries observe The results should also be interpreted with caution. For example, BA.2 in Hong Kong has caused a large-scale epidemic now, and the vaccination rate among the local elderly is low, so it is necessary to be alert to whether there will be more severe diseases.

4. The impact on the epidemic may be limited

Most importantly, from the current data, the impact of BA.2 on the overall global epidemic may be limited.

Although the proportion of BA.2 in new global cases has been increasing recently, the overall number of COVID-19 infections is still declining [1]. This shows that BA.2 may not trigger a new wave of global outbreaks.

Why did Omicron cause such a big outbreak when BA.1 was dominant, while BA.2 spreads faster and is less likely to cause a new wave?

This is because BA.2 is similar to BA.1 in terms of immune escape. From the serum neutralization experiments, the serum neutralization ability of the two sub-strains of the three-dose mRNA vaccine was similar.

The British study also found that the effectiveness of BA.2 and BA.1 after booster shot was similar (BA.1 effectiveness was 63%, BA.2 effectiveness was 70%) [1].

Moreover, the natural immunity formed by infection with BA.1 also has a protective effect on BA.2. A Danish study examined the sequencing results of 140,000 viruses after Omicron dominated for secondary infections. Only 263 secondary infections were found within 1-2 months of infection.

Among them, 190 were secondary infections caused by BA.2, but only 47 cases were first infected with BA.1 and then infected with BA.2, and the rest were first infected with Delta [6]. Young people who were not vaccinated in the secondary infection group had mild symptoms.

This shows that although BA.2 can break through the natural immunity brought about by Omicron BA.1 infection in the past, breakthrough infection is relatively rare, and the symptoms are mainly mild.

Now the vaccination rate in many parts of the world is relatively high, and there have been a large number of BA.1 infections recently.

In this case, the population immunity barrier that BA.2 has to face is very high, so it is difficult to trigger a new wave of epidemics globally.

However, due to the stronger contagion, globally, the emergence of BA.2 may slow down the rate of decline in this wave of Omicron cases, forming a long tail effect.

Moreover, studies have shown that some monoclonal antibody drugs that are effective against BA.1 may have decreased effectiveness against BA.2 [7]. All these require us to remain vigilant about BA.2.

References:：
[1]https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19—15-february-2022
[2]https://en.ssi.dk/-/media/arkiv/subsites/covid19/risikovurderinger/2022/risk-assesment-of-omicron-ba2.pdf?la=en
[3]https://www.forbes.com/sites/williamhaseltine/2022/02/23/whither-the-omicron-family-ba1-ba11-ba2-ba2h78y-ba3/?sh=65ce350d862e
[4]https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1
[5]https://www.medrxiv.org/content/10.1101/2022.02.17.22271030v1.full
[6]https://www.medrxiv.org/content/10.1101/2022.02.19.22271112v1
[7]https://endpts.com/astrazenecas-evusheld-and-gsks-sotrovimab-lose-efficacy-against-omicrons-subvariants/

Is the Omicron BA.2 variant really more infectious and destructive?

(source:internet, reference only)

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