Is the COVID surge more predictable?New Omicron variants provide hints

here we go again. Approximately six months after South African researchers identified a variant of the Omicron coronavirus, two game-altering strains have again surged cases of COVID-19.

Several studies published last week show that the variants known as BA.4 and BA.5 are slightly more contagious than their previous forms of Omicron.¹And some of the immune protection provided by previous infections and vaccinations can be evaded^2,3..

“We are definitely making a comeback in South Africa, which seems to be entirely driven by BA.4 and BA.5,” said Penny Moore, a virologist at the University of the Witwatersland in Johannesburg, South Africa. increase. Subspecies research. “We are seeing a crazy number of infectious diseases. There are six sick people in my lab.”

However, scientists say it is not yet clear whether BA.4 and BA.5 will cause a surge in hospitalizations in South Africa and elsewhere. The waves of previous Omicron infections and the high levels of herd immunity provided by vaccination can blunt many of the injuries previously associated with the new SARS-CoV-2 variant.

In addition, the rise in BA.4 and BA.5, and the rise in another Omicron sect in North America, began to settle the SARS-CoV-2 wave into a predictable pattern, with regular new waves emerging from the circulating stock. May mean that (see “Omicron’s New Identity”). “These are the first signs that the virus is evolving differently,” said Stellenbosch University in South Africa, compared to the first two years of the pandemic, where variants seemed to emerge out of nowhere. Says Tuliode Oliveira, a bioinformatician at the University of Tokyo. the study.

Transmission benefits

By analyzing the viral genome from clinical samples, de Oliveira and his colleagues¹ BA.4 and BA.5 appeared in mid-December 2021 and early January 2022, respectively. Since then, the prevalence of strains has risen and now accounts for 60-75% of COVID-19 cases in South Africa. Researchers have also identified variants in more than 12 other countries, primarily in Europe.

Based on the increase in the number of BA.4 and BA.5 cases in South Africa (from a low of about 1,200 in March to now an average of nearly 5,000 per day), the de Oliveira team has variants. Omicron’s BA.2 Sublineage (In itself, it was a little more contagious than BA.1, the first variant of Omicron). The study has been posted to the medRxiv preprint server and has not yet been peer-reviewed.

The increased transmissibility is a “significant advantage”, and the Belgian Ruben Catholic says that other rapidly prevailing SARS-CoV-2 variants are as large as the advantages that were superior to their predecessors. Tom Wenserias, an evolutionary biologist at the university, said. .. “Looking at all the data together, it seems certain that a significant number of new waves of infection will come.”

Jesse Bloom, a virus evolution biologist at Fred Hutch’s research center in Seattle, Washington, agrees that BA.4 and BA.5 are spreading faster than other Omicron strains. “What’s not clear yet is why they are more contagious,” he says. “One possibility is that they are inherently better at transmitting.” The other is that mutants are better at avoiding immune responses such as antibodies, and people with previous immunity. Is to be able to infect.

Both are closely related to BA.2 — although not exactly clear, Bloom adds (see Pathogen Progression). Both BA.4 and BA.5 have an important mutation in the pesplomer called F486V. It is the viral protein that causes infection and is the primary target of the immune response. Bloom’s team previously discovered that this mutation could help the mutant dodge virus-blocking antibodies.

Further studies suggest that BA.4 and BA.5 are at least partially growing due to their ability to evade the immune response. A team led by Alex Sigal, a virologist at the African Institute of Health in Durban, South Africa, analyzed blood samples of 39 people infected during the first Omicron wave, 15 of whom were vaccinated.²..

In laboratory experiments, the antibodies in these samples were several times less effective in preventing cells from becoming infected with BA.4 or BA.5 than when eliminating the original Omicron strain. However, the antibodies produced by vaccinated people were more potent against new mutants than those from people whose immunity was solely due to BA.1 infection. The study was posted on medRxiv.

Another study³Posted on the ResearchSquare preprint server and led by virologist Xiaoliang Xie of Peking University in Beijing, the antibody caused by the BA.1 infection was also found to be less effective against BA.4 and BA.5. Moore says the results are chimes in her unpublished experiments.

The antigenic escape capabilities of BA.4 and BA.5 are not dramatic, but “enough to cause problems and lead to a wave of infection” — but the mutants are much more than seen in the previous wave. Can not cause serious illness.Sigal, especially in vaccinated people Twitter post.. “They clearly have the benefits of antibody escape, which is one factor that makes them so widespread,” Bloom says.

In South Africa, hospitalizations are gradually increasing from just under 2,000 in COVID-19 in early April, but researchers say that BA.4 and BA.5 put a lot of pressure on health. He says it’s too early to judge. Care system. “Hospitals are open in South Africa and have a strong immunity to the population,” says de Oliveira.

Next wave

BA.4 and BA.5 have been detected in some European countries and North America, where at least soon the variants may not cause the new COVID-19 wave. .. Wenseleers said the immunity of the population may still be high, as closely related variants of BA.2 have just swept Europe. “It probably gives hope in Europe that it will have smaller advantages and cause smaller waves.”

In some parts of North America, we also see the rise of other Omicron substrains with peplomer mutations in some of the same locations as BA.4 and BA.5. Studies show that one such variant (called BA.2.12.1) also has the ability to evade antibodies caused by previous Omicron infections and vaccinations.³ Led by Xie, virologist David Ho is doing another job at Columbia University in New York City. (Ho has not yet reported the team’s data in the preprint, but has shared it with US government officials.)

The emergence of these strains suggests that the Omicron line continues to be profitable by eroding immunity, Ho says. “It’s pretty clear that there are some holes in Omicron that are gradually being filled by these new subvariants.”

As SARS-CoV-2 continues this path, its evolution may resemble that of other respiratory infections such as influenza. In this scenario, the antigenic escape mutations of circulating variants such as Omicron, combined with the weakening of the immune system of the entire population, can be a major driver of the periodic wave of infection. “It’s probably something we should expect to see more and more in the future,” Moore says.

Previous subspecies such as alpha, delta, and omicron differed significantly from their previous subspecies and instead emerged from distant branches of the SARS-CoV-2 family tree.

Venceria and other scientists say that such surprises should no longer be ruled out from SARS-CoV-2. For example, Delta has not completely disappeared, and as global immunity to Omicron and its expanding family grows, Delta’s offspring may resurrect. Whatever their source, new variants appear to emerge approximately every six months, Wenseleers points out and wonders if this is the structure by which the COVID-19 epidemic takes hold.

“This is one way to read the patterns that have been observed so far,” says Bloom. “But I think you need to be careful when estimating general rules from a fairly short observation time frame.”