News

What is known about the Omicron sub-variant BA.2? 

By Prof. Suranjith L Seneviratne and Buddhika Samaraweera

On 26 November 2021, the World Health Organisation (WHO) named the newest SARS-CoV-2 variant at the time, as Omicron. Currently, this variant has spread to over 160 countries. The Omicron variant has 60 changes (mutations) when compared to the original Wuhan SARS-CoV-2 strain. Thirty-two of the changes are in the gene that codes for the spike protein. Three of the changes are at the furin cleavage site and this contributes to the observed increase in infectivity. Subsequently, the WHO designated four lineages to the Omicron SARS-CoV-2 variant. These are B.1.1.529, BA.1, BA.2, and BA.3, respectively. BA.2 has been in the news recently and this article would outline what is known so far about this sub-variant.

What is BA.2? 

BA.2 is a sub-variant of the original Omicron strain and was first classified in the Pangolin database on 6 December 2021. The two Omicron sub-lineages BA.1 and BA.2 are sister clades. They split from each other several months ago and one is not derived from the other. BA.2 has 32 of the same changes as seen in BA.1, and has 28 changes that are different. BA.2 has been designated as a variant under investigation (VUI) by the UK Health Security Agency (UKHSA). The WHO has so far not given any special variant designation to it. 

BA.2 has been referred to by some as the “stealth” Omicron variant. Some SARS-CoV-2 variants of concern (such as Alpha and Omicron – B.1.1.529) produce a negative S-gene result in some multiplex real time polymerase chain reaction (RT-PCR) assays (such as the Thermo Fisher TaqPath assay). This phenomenon is called S-gene target failure (SGTF). This characteristic has been used as a screening method to identify the BA.1 and Alpha variants of SARS-CoV-2. The failure of the S-gene target is caused by a deletion of amino acids 69 and 70 within the spike (S) gene of SARS-CoV-2. The BA.2 sub-variant does not carry the 69-70 deletion and would thus not be identified by SGTF assays. Although there is SGTF in BA.1 (and also in BA.3), this is not seen with BA.2. Thus, the SGTF shortcut cannot be used with BA.2. However, one needs to remember that BA.2 samples would still test positive on SARS-CoV-2 PCR and lateral flow testing, but would need genetic sequencing to be further identified as the BA.2 sub-variant. In addition, as the Delta variant is increasingly disappearing from many countries, a falling proportion of SGTF’s would give us an idea of the spread of BA.2 compared to BA.1.    

Where is it found?

The first sequence of the BA.2 sub-variant was submitted to a global coronavirus data sharing platform by the Philippines in November 2021. Since then, over 15,000 sequences of BA.2 have been uploaded and currently it has been detected in over 50 countries. Denmark has so far recorded the highest number of infections. We need to remember that Denmark has a high rate of viral genome sequencing and this may account for the high numbers noted here. Presently, BA.2 has become the dominant SARS-CoV-2 stain in Denmark. Some of the other countries with BA.2 includes: India, Norway, Sweden, Singapore, the UK, and the US. In the UK, between 8 and 15 January 2022, the proportion of BA.2 cases increased from 0.2% to 0.8% and the majority of cases were from London and the South East. The BA.2 sub-variant may prolong the current Omicron wave in many countries, but a reassuring finding from South Africa is that although a high proportion of cases are due to BA.2, it is not leading to another wave of cases. 

What are its effects?

There are many ongoing studies comparing the characteristics of BA.2 and BA.1 with regard to its transmissibility, virulence, and immune escape. There is some indication that it is more transmissible and this is especially so for unvaccinated individuals. The UK Health Security Agency (UKHSA) has found BA.2 to be able to spread faster than BA.1. They found BA.2 to have a comparatively higher growth rate in all observed areas of England and that BA.2 was 50% more transmissible than BA.1. The amount of virus in the upper airway is similar in BA.1 and BA.2-infected individuals. According to the UKHSA, there is a higher secondary attack rate amongst contacts of BA.2 cases in households than for contacts of other Omicron cases. According to initial reports coming out from Denmark, there is no difference in the rates of hospitalisation between BA.2 and BA.1. Similarly, early data from India did not find a difference in infection severity between BA.2 and BA.1. 

It is still expected that vaccines have a protective effect against severe illness from BA.2. A recent study from the University of Oxford, found similar levels of neutralisation of BA.2 and BA.1 pseudoviruses, by serum obtained from vaccinated individuals. Antibodies elicited by BA.1 will likely react reasonably well against BA.2. Thus those infected with one of the Omicron sub-lineages should have good immunity against the others. According to recent data released by the UKHSA, three vaccine doses were 70% effective at preventing symptomatic BA.2 infection, two weeks after a booster dose. The corresponding effectiveness against BA.1 was 63%. In those who had only received two vaccine doses, the effectiveness 25 weeks later was low, at 13% and 9% against BA.2 and BA.1, respectively. This highlights the importance of persons receiving a booster vaccine dose, especially in the context of the rapid spread of both BA.1 and BA.2 in many countries.     

Conclusions

It is a characteristic of viruses to evolve and mutate. Thus, the expectation is that new variants would continue to emerge. The detection of SARS-CoV-2 sub-variants is not new. The Delta variant also had several sub-variants, but all of them were referred to as Delta. BA.2 earned its own designation due to the detection of high numbers across several countries. At the present time, it remains unclear if BA.2 would behave differently to BA.1. However, early indicators point to many similarities. Further clarity would be possible as more cases are reported from the affected countries.