As India Sees Two Cases of New Omicron Sub-Variants, How Worried Should We Be?

New Delhi: India’s genomics consortium announced on May 22 that cases of newer sub-variants of omicron – BA.4 and BA.5 – have been found in the country. The presence of BA.4 was confirmed in a 19-year-old female from Tamil Nadu and BA.5 was detected in an 80-year-old male from Telangana.

Both patients, notably, had no travel history. In other words, the sub-variants are now spreading locally among populations just like other past variants and sub-variants of the novel coronavirus did in India and elsewhere. But do we really need to be worried about them?

“I don’t think we need to be…There is not much evidence at the moment that we should be doing so,” eminent virologist Gangandeep Kang, a professor at the Christian Medical College, Vellore, told The Wire.

BA.4 and BA.5 continue the branching legacy of the omicron variant. The variant emerged as BA.1 in December 2021. Shortly after came BA.2. Now, we have BA.3, BA.4, BA.5 and BA.2.12.1.

Of all the variants that have come up thus far, omicron is the one which has had the most sub-variants.

BA.4 and BA.5 are currently driving uptick in COVID-19 cases in South Africa. According to the last weekly epidemiological update issued by the World Health Organisation (WHO) on May 18, BA.4 and BA.5 have been detected in 20 and 19 countries respectively. But the question is: can they put pressure on health systems to an extent that they may crack – something we saw with earlier variants, especially in the case of delta.

On the South African experience of BA.4 and BA.5, the WHO update says there has been a “a moderate increase in hospital admissions, although this rise has been significantly lower than that observed during the emergence of Omicron in late 2021.”

To put things in perspective, the original version of omicron itself led to a smaller number of hospitalisations compared to delta.

In an interview with The Wire earlier this month, Tulio de Oliveira, a professor of bioinformatics at the Universities of KwaZulu-Natal and Stellenbosch, said these new sub-variants were driving the surge in all nine provinces of the country.

The WHO update goes on to add that in Portugal, where BA.5 seems to be in the driver’s seat, hospital and ICU admissions remained stable as of May 13.

But that doesn’t seem to be the case with BA.2.12.1, which had led to a fresh wave of COVID in the US. It has resulted in somewhat a substantial increase in hospitalisations in the US – something that the WHO update also conceded when it said that admissions there had increased by 19% in the week starting May 9.

CNBC reported on May 20 that the hospitalisations had gone up by 25% as compared to the previous week, quoting the data from US Centres for Disease Control and Prevention. This sub-variant is now present in 38 countries, however, it has not been found in India so far.

The UN health body has also indicated that the proportion of new forms of omicron is increasing in the existing overall pie of all variants and sub-variants. So, the number of cases infected with sub-variants of omicron is only going to go up in the weeks to come.

But these facts only indicate the evolutionary process of SARS-CoV-2. At the end of the day, it is an RNA virus and is expected to undergo a large number of mutations as a consequence. Add to this the fact that the virus is, itself, under a lot of pressure to simply sustain its existence amid its fight with vaccines and thus, the only way the virus can survive is by mutating endlessly.

Like Kang, the WHO has also maintained that results from more studies are needed to ascertain the full impact of these new sub-variants. But one important study, which was posted on preprint server bioRxiv on May 2, made a few important claims.

What’s new in the sub-variants?

First, all these new sub-variants – BA.2.12.1, BA.2.13, BA.4 and BA.5 – contain the L452 mutation. Incidentally, this mutation was also present in the Delta variant and provided it with the ability to escape the immunity granted by a previous infection and also attach better with human cells.

In other words, delta was able to be transmitted efficiently because of this particular mutation, which has now been found by a bunch of Chinese scientists in the newer sub-variants of omicron as well.

Secondly, the paper also said that unlike BA.2, BA.4, BA.5 and BA.2.12.1 had a “stronger” capacity to evade immune protection granted by three doses of vaccines.

More strikingly, even those who had been infected with BA.1 – the first omicron sub-variant – were not spared from a reinfection with newer sub-variants, even if they had been jabbed. In other words, antibodies generated after an infection with an earlier sub-variant of omicron were not good enough to stand strong against subsequent sub-variants of the same variant.

“But why should one be surprised by reinfections,” Kang wondered. Since a large chunk of the world’s population has already been infected once or more, it is obvious that new infections are going to be reinfections only.

She also said it wouldn’t be prudent to make head-on comparisons as to whether one variant or sub-variant is more capable of causing reinfections than another. “The population that existed in the beginning of the pandemic is not the same now. Infections and vaccination have changed the profile of host populations,” Kang argued.

The WHO has, so far, refused to give separate variant of concern (VoC) classifications to BA.4 and BA.5, since omicron is already classified as a VoC. But the European Centre for Disease Prevention and Control (ECDC), on May 13, went ahead and classified them as separate VoCs, owing to their different “antigenic properties” (the capacity of a virus to trigger a response) as compared to BA.1 and BA.2.

This is the first time in the pandemic that an international public health agency has classified sub-variants of the same variants as separate VoCs. “Naming or not naming them [in a particular way] doesn’t make much of a difference in public health till a new sub-variant starts overwhelming health systems. Rest all of it is for agencies and individuals,” Kang said, though she sided with the WHO’s stand.

So, while the new sub-variants lead to an increase in hospitalisations and evade immune protection granted by previous infection and/or vaccination, the only respite is they don’t seem to cause a ‘severe disease’, yet, as the Global Alliance for Vaccines and Immunization (GAVI) noted in its explainer. There has not been sufficient evidence yet to say anything about the change in the severity of the disease caused by these new sub-variants.

What next?

The million dollar question right now is: what can we expect from hereon out? Can these new sub-variants lead to major global upsurges? Kang believes not, “until they acquire certain characteristics that they still don’t have,”; primarily the potential to spread more and spread faster.

All hopes are now pinned on variant-proof or pan-coronavirus vaccines. These vaccines are expected to provide protection against all existing and future variants of the virus. While some of them introduce multiple antigens in the body to ward off multiple variants, others introduce a single antigen which will kill all variants. Either way, the result is the same; only the mechanism differs. These vaccines are under various stages of pre-clinical trials [trials preceding human trials].

Till the time they see the light of the day, however, policymakers have to accept the fact that this virus may still spring up surprises in the form of new variants and sub-variants. Responsible countries are expected to have a broad approach against all such scenarios without slipping at all on genome sequencing, in order to understand what new variant is circulating.

“This is not rocket science, after all,” Kang said.