Virus World

The BA.2 virus -- a subvariant of the Omicron coronavirus variant -- isn't just spreading faster than its distant cousin, it may also cause more severe disease and appears capable of thwarting some of the key weapons we have against Covid-19, new research suggests.  New lab experiments from Japan show that BA.2 may have features that make it as capable of causing serious illness as older variants of Covid-19, including Delta. And like Omicron, it appears to largely escape the immunity created by vaccines. A booster shot restores protection, making illness after infection about 74% less likely. BA.2 is also resistant to some treatments, including sotrovimab, the monoclonal antibody that's currently being used against Omicron.  The findings were posted Wednesday as a preprint study on the bioRxiv server, before peer review. Normally, before a study is published in medical journal, it is scrutinized by independent experts. Preprints allow research to be shared more quickly, but they are posted before that additional layer of review. "It might be, from a human's perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease," says Dr. Daniel Rhoads, section head of microbiology at the Cleveland Clinic in Ohio. Rhoads reviewed the study but was not involved in the research.  The US Centers for Disease Control and Prevention is keeping close watch on BA.2, said its director, Dr. Rochelle Walensky. "There is no evidence that the BA.2 lineage is more severe than the BA.1 lineage. CDC continues to monitor variants that are circulating both domestically and internationally," she said Friday. "We will continue to monitor emerging data on disease severity in humans and findings from papers like this conducted in laboratory settings."

BA.2 is highly mutated compared with the original Covid-causing virus that emerged in Wuhan, China. It also has dozens of gene changes that are different from the original Omicron strain, making it as distinct from the most recent pandemic virus as the Alpha, Beta, Gamma and Delta variants were from each other. Kei Sato, a researcher at the University of Tokyo who conducted the study, argues that these findings prove that BA.2 should not be considered a type of Omicron and that it needs to be more closely monitored.  "As you may know, BA.2 is called 'stealth Omicron,' " Sato told CNN. That's because it doesn't show up on PCR tests as an S-gene target failure, the way Omicron does. Labs therefore have to take an extra step and sequence the virus to find this variant. "Establishing a method to detect BA.2 specifically would be the first thing" many countries need to do, he says. "It looks like we might be looking at a new Greek letter here," agreed Deborah Fuller, a virologist at the University of Washington School of Medicine, who reviewed the study but was not part of the research.

CRISPR gene editing has created chickens that resist a common virus. It may be possible to use the same technique to make poultry resistant to bird flu too. The altered chickens showed no signs of disease even when exposed to high doses of the avian leukosis virus (ALV). The virus is a problem for poultry farmers around the world, says Jiri Hejnar at the Czech Academy of Sciences. Infected birds become ill, emaciated and depressed, and often develop tumours. The virus gets into cells by binding to a protein called chicken NHE-1 (chNHE-1). Hejnar’s team has previously shown that deleting three DNA letters from the chNHE-1 gene that makes this protein prevents ALV from infecting chicken cells.

The challenge was to make this change in entire animals rather than just in a few cells. No strains of chickens naturally have this mutation, so it can’t be done by breeding alone. But genetically modifying chickens is more difficult than modifying other animals such as pigs. The conventional method is to extract so-called primordial germ cells, alter them outside the body and then add the modified cells to embryos inside freshly laid eggs. This approach was used to create CRISPR chickens in 2016, but the success rate is extremely low. In 2017, Hejnar developed a better method: using altered germ cells to restore semen production in sterilised cockerels. His team then went on to create a cockerel with sperm that have the precise deletion in the chNHE-1 gene. By crossing its offspring, they have produced a flock of white leghorn chickens that have this deletion in both copies of the gene.

A company called Biopharm is now in discussion with poultry producers in Vietnam and China about introducing this change into commercial breeds. “It’s quite simple to do,” says Hejnar. Hejnar also plans to use CRISPR to make chickens resistant to other viruses, such as bird flu. This would make us all safer: bird flu viruses sometime kill people and there are fears a mutant strain could cause a deadly global pandemic. However, there is still opposition to GM foods in many countries. It remains to be seen whether consumers will find CRISPR chickens to their taste.

Published in PNAS:

https://doi.org/10.1073/pnas.1913827117