What do we know about the new sub-variants BA.4 and BA.5

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Two new Omicron variants, BA.4 and BA.5, which have appeared in South Africa and have begun to spread to Europe and other countries, raise questions and questions among scientists as to whether they could trigger a new outbreak. Covid-19. On the other hand, some prefer to look at the more optimistic side: that the two variants are signs that the coronavirus is becoming more predictable.

Nearly six months after locating the original Omicron in South Africa, researchers there found two new “sprouts” that have caused a new wave of infections in the country (about 5,000 a day compared to 1,200 in March). Several studies in recent days have shown that BA.4 and BA.5 are slightly more contagious than “normal” Omicron (BA.1) and Omicron 2 (BA.2) and that they may be somewhat superior to immune protection caused by a previous Covid-19 infection (natural immunity) or vaccination.

“We are clearly entering a new upsurge in South Africa that seems to be caused entirely by NE.4 and NE.5. “We are seeing insane numbers of infections,” Penny Moore, a professor of virology at Witwatersrand University in Johannesburg, told Nature.

However, scientists are still unsure whether BA.4 and BA.5 will cause a new wave of hospitalizations in South Africa or elsewhere, as large sections of the population are now either already vaccinated or infected with previous Omicron variants.

On the other hand, the emergence of the two new subtypes probably signals that the SARS-CoV-2 virus has entered a more predictable period, with new smaller waves appearing periodically from its strains already in circulation. “These are the first signs that the virus is evolving differently now than it did in the first two years of the pandemic, when variants seemed to be popping up out of nowhere,” said Tulio de Oliveira, a bioinformatics specialist at Stellenbosch University in South Africa.

Analyzing viral genomes from clinical specimens, Oliveira and his colleagues, who made the relevant pre-post on medRxiv, found that BA.4 and BA.5 first appeared in mid-December 2021 and early January 2022, respectively, but only recently in their presence. Today they together account for 60% to 75% of new cases in South Africa, and have already been identified in several European countries.

Oliveira estimated that BA.4 and BA.5 spread slightly faster than Omicron 2, which in turn was slightly more contagious than the original Omicron. Evolutionary biologist Tom Wenceleers of the Belgian Catholic University of Leuven said that “given all the data, it looks like a significant wave of new infections is sure to come.”

Antiviral biologist Jesse Bloom of the Fred Hutch Research Center in Seattle agrees that NE.4 and NE.5 are spreading faster than previous Omicrons. As he says, “what is unclear is why they are more contagious. One possibility is that inherently they are simply better at transmitting. ” Another possibility is that they are better at escaping natural and vaccine immunity.

The two new subtypes are closely related to Omicron 2, and both carry a key mutation (F486V) in their spike protein, which is mainly targeted by vaccines, which may affect the effectiveness of vaccines.

A study by South African virologist Alex Seagal, also pre-published on medRxiv and analyzed blood samples from 39 people infected with the first Omicron wave and 15 also vaccinated, showed that their antibodies were several times less effective than protecting with BA.4 or BA.5, than with BA.1 infection. The antibodies of the vaccinated, however, were stronger against BA.4 and BA.5 than the natural antibodies after BA.1 infection.

Another study by Chinese virologist Xiaoliang Xie of Peking University, pre-published in ResearchSquare, also found that antibodies after BA.1 infection were less potent against BA.4 and BA.5.

According to Seagal, this increased ability of new variants to escape immunity, while not dramatic, “is enough to cause problems and create a wave of infections.” However, he estimated that BA.4 and BA.5 are not considered likely to cause more serious disease than the previous Omicron wave. At the moment, hospitalizations are slowly rising in South Africa, but scientists say it is too early to say for sure whether BA.4 and BA.5 can put particular strain on health systems.

Although new subtypes have been detected in several European countries and in North America, they are not believed to immediately cause a new wave of infections, as Omicron 2 has just “scanned” European countries and their population immunity is still high. According to Wenzellers, “this gives hope that in Europe the BA.4 and BA.5 may have a smaller advantage and will cause a smaller wave.”

The previous variants Alpha, Delta, Omicron etc. differed from the new sub-variants, as they had sprung from distant “branches” of the coronavirus family tree, while NE.4 and NE.5 are the most anticipated evolutionary adaptations. On the other hand, many scientists can not rule out new surprises of the Delta type, which incidentally has not completely disappeared and some “branch” of it may emerge at some point. Regardless of their source, new variants of the coronavirus appear to come to the fore every six months or so.

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