New Omicron Subvariant Detected In 10 Indian States May Be 'Alarming' In Nature, Israeli Expert Says. What We Know So Far

An Israeli researcher wrote that it is “too soon” to say whether BA.2.75 will be the next dominant variant. However, he believes that BA.2.75 is "alarming" because it may imply a trend to come.

A new Omicron subvariant has been detected in about 10 states in India. The subvariant, called BA.2.75, may be "alarming" in nature, an Israeli expert said on July 3, news agency IANS reported. 

The Indian health ministry has not yet confirmed the detection of the subvariant in the country. Dr Shay Fleishon, with the Central Virology Laboratory at Sheba Medical Center in Tel Hashomer, wrote in a series of tweets that 85 sequences of BA.2.75 have been obtained so far, mainly from 10 states in India and seven countries. He said that no transmission could be tracked based on sequences outside India yet. 

Geographic Distribution Of BA.2.75

Fleishon posted a table depicting the geographic distribution of the cases. The capital of India, Delhi, was found to have one case of the new subvariant. The states of Haryana, Himachal Pradesh, Jammu and Kashmir, Karnataka, Madhya Pradesh, Maharashtra, Telangana, Uttar Pradesh and West Bengal have six, three, one, ten, five, twenty-seven, two, one, and thirteen cases respectively. 

Meanwhile, Japan, Germany, the United Kingdom, Canada, United States, Australia, and New Zealand have one, two, six, two, two, one, and two cases of new subvariant respectively.

“Too Soon” To Say Whether BA.2.75 Will Be Next Dominant Variant: Shay Fleishon

Fleishon further wrote that it is “too soon” to say whether BA.2.75 will be the next dominant variant. However, he believes that BA.2.75 is "alarming" because it may imply a trend to come.

He also wrote that in recent months, there has been a trend of second generation variants based on B.1.1.529 lineages, namely BA.1, BA.2, BA.3, BA.4, and BA.5. 

These second generation variants were based on Omicron lineages with mutations in the S1 section of the spike protein, specifically in the RBD. The receptor-binding domain or RBD is the part of the spike protein of SARS-CoV-2 where the virus attaches itself to host cells. 

Fleishon noted that the rise in these subvariants has been at a level not seen in second generation variants of other variants of concern (VOCs). 

He said the fact that such a divergent second generation variant can succeed inter-host is "alarming", which means that if BA.2.75 will not succeed, and even if it will, other second generation variants might grow better over time.

It Is Worth Keeping A “Close Eye” On BA.2.75: Tom Peacock

Tom Peacock, a virologist at the Imperial Department of Infectious Disease, London, wrote on Twitter that it is worth keeping a "close eye" on BA.2.75. This is because the new variant has lots of spike mutations, and is apparently growing rapidly and widely spreading across geographical regions, he explained.

More About BA.2.75, Its Mutations, And Comparison With Other VOCs

Bloom Lab, a Seattle-based lab studying molecular evolution of proteins and viruses and associated with Fred Hutch research institute in the United States, wrote in a tweet last week that the institute said the subvariant is flagged by Tom Peacock is "worth tracking", as it has appreciable antigenic change relative to its parent BA.2. According to the lab, the two key mutations are G446S and R493Q. 

The lab wrote on Twitter that G446S is at one of the most potent sites of escape from antibodies elicited by current vaccines that still neutralise BA.2. It added that for immunity from vaccines or early infections, adding G446S to BA.2 will decrease neutralisation.

The lab also wrote that G446S will have less effect on antibodies of people with prior BA.1 breakthrough infection. Therefore, BA.2.75's antigenic advantage relative to BA.2 will be most pronounced in people who have not had BA.1 exposure, the lab explained.

The Omicron subvariants BA.4 and BA.5, which are more infectious than past strains and can more easily escape antibodies from vaccines and previous infections, may soon become the dominant strains in Europe and the US, according to health experts. These strains, which were first spotted by scientists in South Africa in April, have been detected in dozens of countries worldwide. The subvariants are spiking globally because they can spread faster than other circulating variants, especially BA.2.

Bloom Lab wrote on Twitter that BA.4 and BA.5 show a three-fold drop in neutralisation relative to BA.2. The antibody-escape calculator for the lab suggests that BA.2.75 will have a drop in neutralisation similar to that for BA.4 and BA.5 in people without BA.1 breakthrough infection, but less of a drop in people with a prior BA.1 infection.

This is because BA.4 and BA.5 have F486V mutation, which escapes antibodies from both the current vaccine and BA.1 breakthrough. However, BA.2.75 lacks F486V but has G446S, which escapes antibodies from current vaccines. However, the antibody-escape is less in people with prior BA.1 breakthrough infection.

According to Bloom Lab, there is an evolutionary role for R493Q, which is seen in BA.2.75 as well as BA.4 and BA.5. Though R493Q is not a major antigenic mutation, it enables F486V mutation in BA.4 and BA.5, and G446S mutation in BA.2.75. 

R493Q increases the virus's affinity to ACE2, which is the receptor for the SARS-CoV-2 viral entry. 

The lab stated that BA.2.75 will have antibody-espace similar to that for BA.4 and BA.5 with respect to current vaccines.