Explained: What are BA.4 and BA.5 sub-variants of Omicron, and can they lead to a Covid surge in India?

The Indian Express takes a look at what we know about BA.4 and BA.5 sub-variants of Omicron so far:

How are the two new Omicron sub-variants different from the ones that caused the third wave of Covid-19 in India?

Firstly, the new sub-variants are not all that new. They were first identified in South Africa in January this year, while India was witnessing the third wave of Covid-19. Over the next four months, BA.4 and BA.5 became the dominant variants in circulation in that country – collectively replacing 55 per cent of the other Covid-19 variants, according to the National Institute of Communicable Disease-South Africa.

The two sub-variants have since been detected in several European countries and the United States. The European CDC has declared the two as ‘variants of concern’, anticipating “a significant overall increase in Covid-19 cases in the coming weeks and months.”

What concerned scientists the most were two mutations that both the sub-variants carried on their receptor binding domain – the part of the virus’ spike that attaches to the human cells and enters the body.

The F486V mutation, previous lab studies show, is one of the biggest escape mutations for other Omicron sub-variants, meaning it makes the virus better able to evade the antibodies from previous infection or vaccination.

Dr Anurag Agarwal, former head of INSACOG and the chair of WHO’s Technical Advisory Group on Virus Evolution, in a tweet said, “Antigenically – quite dissimilar to BA.1, so humoral cross-protection will decline. (Antibodies will be less effective).”

This, coupled with the waning immunity from vaccines, is likely to lead to the two sub-variants propagating, the European CDC said.

The other L452R mutation, which was previously found in the Delta variant, is known to enhance the virus’ ability to enter human cells. A laboratory study from China also shows that Omicron variants with the L452R mutations are better able to infect lung cells in mice. The Omicron variant led to less severe disease in most places, including India, because it mainly affected the upper respiratory tract, unlike Delta that severely affected the lungs leading to higher hospitalisations, requirement for oxygen, and deaths.

Are the two sub-variants likely to cause more severe disease, hospitalisations?

The good news, however, is that on-ground, BA.4 and BA.5 don’t seem to be causing an increase in hospitalisations and deaths in South Africa. “Wave of infections in SA has peaked with, so far, low hospitalisations and deaths,” said director of Centre for Epidemic Response and Innovation-South Africa Tulio de Oliveria in a tweet. He is also a member of the WHO group tracking the evolution of Covid-19. He added, “Interesting that, so far, in countries with a large BA.2 wave, the BA.4 and BA.5 seem to be increasing slowly.”

BA.2 was the dominant sub-variant in India during the third wave. In fact, an analysis of the global database of Covid-19 genome sequences shows that BA.2 accounted for 62 per cent of the sequences from India over the last two months.

The European CDC also said, “There is currently no indication of any change in severity for BA.4/BA.5 compared to previous Omicron lineages.”

Dr Sudhanshu Vrati, the current head of India’s genomic sequencing consortium INSACOG, agreed.

So, are the variants likely to cause another surge in cases in India?

Dr Vrati said, “We already have a four-month experience from other countries on the two sub-variants; the initial concern was because of the L452 mutation seen in the Delta variant. However, so far, there has been no co-relation of these with an increase in the severity of disease, hospitalisations or deaths. And, that is likely to be the case in India as well.”

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As for the increase in the number of cases – as seen during the January Omicron-variant driven wave when cases shot up but hospitalisations did not increase proportionally – he said, “A significant proportion of our population has had the infection and been vaccinated. The sub-variants are unlikely to cause havoc. As for increase in the number of cases, we saw that even now with the standard Omicron variant in Delhi-NCR, the virus will always find the ones with lower immunity.”

He added that there was no need for people to be worried, but that genomic sequencing must continue to watch out for new variants that might lead to more cases or severe disease.