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Surge of 300 COVID variants with increased immune escape properties

Omicron sub-variants are showing signs of “increased transmissibility and properties of immune escape”, the World Health Organisation has warned, but reduced surveillance has limited efforts to understand the ramifications.

Dr Maria Van Kerkhove, head of the UN agency’s technical team for COVID, said that more than 300 versions of Omicron are now circulating globally – not causing more severe disease, but developing some qualities “of concern”, reports The Telegraph.

“They are all showing increased transmissibility and properties of immune escape,” she said. “We don’t see a change in severity yet and our vaccines remain effective, but we must remain vigilant.”

Although no single variant is currently dominant, three are spreading quickly: XBB, which has driven a new wave of infections in Singapore, and BQ.1 and BQ.1.1, spreading in Europe and responsible for around 11% of cases in the United States.

Available data suggest XBB, spotted in 26 countries, may be the best at evading immunity. In one study by researchers in China, the variant partially evaded antibodies generated by a previous infection with BA.5, an older Omicon sub-variant.

XBB hasn’t yet been detected in the US. But its child has.

XBB.1 was first detected in the US on 15 September, and made up 0.26% of cases genetically sequenced over the past 15 days, Raj Rajnarayanan, assistant dean of research and associate professor at the New York Institute of Technology campus in Jonesboro, Arkansas, told Fortune. He cited data from GISAID, an international research organisation that tracks changes in COVID and the flu virus.

Only 16 XBB.1 cases have been detected in America so far, and most have been found in New York – considered a bellwether state because of its volume of incoming international travellers and robust genetic sequencing capabilities, Rajnarayanan said.

XBB is a combination of two different Omicron spawns. It, along with BQ.1.1, is considered to be the most immune-evasive COVID variant so far, surpassing the immune-evasiveness of shared ancestor BA.5, dominant around the globe this summer.

Scientists, including top US infectious disease expert Dr Anthony Fauci, expect an autumn and winter wave of cases in the US that begins to surge in October and peaks in January. It’s still unclear which COVID variant may fuel that wave.

Last week the US Centres for Disease Control and Prevention (CDC) announced that heavyweight Omicron spawn BQ.1 and BQ.1.1 are in the US, and quickly rising. With XBB present as well, the scene has been set for a potential battle royal between two formidable variants.

Compared to XBB, XBB.1 features just “one small change” to the spike protein, which the virus uses to attach to and infect cells.

The impact of the alteration is unknown, according to Rajnarayanan.

It’s one of multiple XBB offspring being eyed by variant trackers globally that are helping fuel Singapore’s wave, despite a significantly vaccinated and boosted population.

Dr Jesse Bloom, an expert on viral evolution at the Fred Hutchinson Cancer Research Centre in Seattle, said variants were evolving “strikingly rapidly” and it is “too early to predict” which will have the biggest impact over winter.

But the WHO warned that reduced global surveillance networks means it is harder to track and understand this swarm of new sub-variants.

“There are millions of cases being recorded weekly. But surveillance has declined, testing has declined, sequencing has declined – in turn limiting our ability as an organisation, with our expert networks worldwide, to assess these (variants),” Van Kerkove said.

New restrictions unlikely

In Singapore, the Health Minister has said the new wave triggered by XBB has seen cases leaping from around 3 000 a day in late September to 8 500 on 18 October, although the number of people in intensive care has remained steady.

Dr Amesh Adalja of the Johns Hopkins University Centre for Health Security, said: “It’s important to remember immunity is not an on or off switch. It’s a spectrum of protection.

“Even if XBB can get around some immunity provided by prior infections, it will still be unable to cause severe disease because other aspects of immunity like T-cells are really good … we’re shifting COVID-19 to the outpatient side – to something that doesn’t require hospitalisation.”

Professor Ravi Gupta, a professor of clinical microbiology at the University of Cambridge, said they new variants still have a “very common set” of characteristics and appear to be evolving in the same direction.

“That variants are picking up similar sets of mutations is a sign there’s quite a lot of population level immunity out there that the virus is trying to overcome,” he said. “It would take a 'super hot' variant to take over the world.”

He said the increased immune evasion is not comparable to previous jumps.

However, Rajnarayanan isn’t worried about one variant in particular right now, as current Omicron spawn are all picking up similar mutations that confer advantages like increased transmissibility and additional ability to evade immune systems.

He’s keeping a close eye on XBB. But he’s keeping a closer eye on BQ.1.1, and parent BQ.1, with both variants having broken out into their own categories from ancestor BA.5.

BQ.1.1 is surging in New York and also rising in European countries like Germany, where Oktoberfest celebrations may have served as super-spreader events.

Its extreme immune evasiveness “sets it up to be the principal driver of the next US wave in the weeks ahead”, said Dr Eric Topol, a professor of molecular medicine at Scripps Research and founder and director of the Scripps Research Translational Institute.

He told Fortune that scientists won’t know to what extent it evades vaccine protection, if it does, until it reaches 30% to 50% of cases somewhere. “It’s not going to wipe out vaccine efficacy, but it could put a dent in protection against hospitalisations and death,” he said.

A dwindling toolbox and an upcoming fight

Both XBB and BQ.1.1 are known to escape antibody immunity, rendering useless monoclonal antibody treatments used in high-risk individuals with COVID. According to a study last month out of Peking University’s Biomedical Pioneering Innovation Centre in China, both escape immunity from Bebtelovimab, the last monoclonal antibody drug that is effective on all variants, as well as Evusheld, which works on some. And both could lead to more severe symptoms, the authors wrote.

The ability of XBB to evade immunity is “extreme” approaching the level of immune evasion shown by SARS, a coronavirus that infected thousands and caused nearly 800 deaths in the early 2000s, the authors added.

BQ.1.1 and XBB are so distinct from other Omicron strains that they should be granted new Greek letter names, like Pi or Rho, by the WHO, Topol said.

Whether BQ.1.1 and XBB eventually battle for dominance in the US or anywhere else remains to be seen. They may even find themselves sparring in one host, and the result could be a strain that combines the two, Ryan Gregory, a professor of evolutionary biology at the University of Guelph in Ontario, Canada, told Fortune. Or descendants of the two might find themselves battling it out instead.

With the virus’ record rate of evolution, the possibilities are seemingly endless.

“If people aren’t boosted and haven’t been infected in a little while, you’re going to see lots of transmission, you’re going to see direct competition,” Gregory said. “We’re basically going to see them both move into whatever hosts are available.”

New COVID variants gaining ground

BA.4.6
Parental strain: BA.4
Prevalence: An estimated 12.2% of new cases this week
What to know: The share of BA.4.6 infections has been increasing for “several months”, said William Hanage, an infectious disease epidemiologist at the Harvard TH Chan School of Public Health.
Mutations: The strain is a descendent of the BA.4 omicron subvariant, but contains a couple of key mutations to the spike protein that health experts speculate may give it an advantage. One such mutation, R346T, has been seen in previous variants and is thought to be associated with immune evasion. Initial data suggest BA.4.6 has been able to evade immunity, “but not to a high extent”.

BQ.1 and BQ.1.1
Parental strain: BA.5
Prevalence: Combined, an estimated 11.4% of new cases this week
What to know: BQ.1 and BQ.1.1, the newest strains, have gained the attention of top health experts due to its rate of increase since it was first identified in early September.
Dr Peter Hotez, a paediatrician and dean of the National School of Tropical Medicine at Baylor College of Medicine Houston, called BQ.1.1 the “most likely candidate” to drive a new COVID-19 wave, if that were to happen in the coming months.
Mutation: The strains also contain the R346T mutation, been linked to immune evasion.

BF.7
Parental strain: BA.5
Prevalence: An estimated 5.3% of new cases in past week
What to know: Also picked up a few mutations that will evade vaccine induced immunity.
Mutation: BF.7 is another descendent of BA.5 with the R346T mutation.

The good news

USA Today reports that although most of the emerging variants contain a mutation that may be able to evade vaccine-induced and natural immunity, health experts say the new bivalent booster should provide some protection against the newest strains. The boosters combine the original COVID-19 vaccine with a reformulation that targets the BA.4 and BA.5 versions of the omicron variant.

 

The Telegraph article – Swarm of Covid sub-variants show ‘increased transmissibility and immune escape’ (Open access)

 

Fortune article – The XBB family of Omicron has landed in the U.S. Here’s what it means for this fall’s COVID wave (Open access)

 

USA Today article – Move aside, BA.5: These new COVID variants are gaining ground in the US (Open access)

 

See more from MedicalBrief archives:

 

Gauteng reports 10 cases of Omicron sublineage XAY

 

COVID sub-variant spreads and new symptoms emerge

 

NICD statistics: COVID cases rise as two Omicron sub-lineages spread across SA

 

Omicron sub-variant BA.2 warning for US as European cases surge

 

 

 

 

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