New Coronavirus News from 17 Feb 2022

Stealth Omicron BA.2 COVID Variant Could Be More Dangerous, Immune-Resistant Than BA.1—Study [Newsweek, 17 Feb 2022]

BY ED BROWNE

The Omicron COVID sub-variant BA.2 may be more dangerous than BA.1 and could pose a greater risk to public health, according to new research.

BA.2 has made headlines in recent weeks and is the subject of ongoing research after overtaking the previously dominant BA.1 Omicron type in countries like Denmark and South Africa.

Research has found that BA.2 has a significant transmission advantage over BA.1, meaning it has the potential to spread faster through populations. But other key characteristics about the variant, such as whether it leads to increased hospitalization or is more resistant to vaccines, have yet to be conclusively determined.

Early data from the U.K.'s Health Security Agency (HSA) has suggested that vaccines are as effective against BA.2 as BA.1 in terms of preventing symptomatic disease, based on people who had a booster shot.

However, on Tuesday, dozens of researchers from Japan released a study in which they said they found that BA.2 may in fact be more pathogenic—capable of causing disease—and more resistant to previous immunity than BA.1. It should be noted that the study hasn't yet gone through the peer review process in which its quality and validity will be assessed.

The researchers infected hamsters with BA.1 and then obtained convalescent sera—essentially blood samples—from them after their bodies had elicited an immune response, meaning their blood contained antibodies.

They then exposed samples of BA.1 and BA.2 to these antibodies to see what would happen.
The researchers found that BA.2 was 2.9 times more resistant to the hamster samples than BA.1 was.

They further tested this finding in mice by immunizing them with cells expressing the spike protein of BA.1 and once again tested their antibodies against BA.1 and BA.2. This time, they found that BA.2 was 6.4 times more resistant than BA.1.

In addition, the researchers infected hamsters with BA.2 and BA.1 and found that the BA.2 group exhibited more health disorders such as body weight loss than in those infected with BA.1. They also found that the amount of BA.2 virus was higher in the hamsters' lungs than that of BA.1.

Recognition as a Variant of Concern
The researchers say that based on their findings, BA.2 should be given its own Greek alphabet letter and be "recognized as a unique variant of concern."

There are limitations to bear in mind, however. As mentioned, the study hasn't yet been peer reviewed and so its findings must be taken with a grain of salt for now. In addition, animal and cell culture models don't always translate accurately to humans.

Jeremy Kamil, associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek that the study "looks highly credible and rigorous" and was from "an excellent research group", but noted: "I think it's always hard to translate differences in animal and cell culture models to what's going on with regards to human disease. That said, the differences do look real.

"I'd also stress that immunity to BA.1 will mitigate against, and in most cases fully protect people from, BA.2 infection in the near term."

Ian Jones, professor of virology at the University of Reading in the U.K., said that he "can't see any flaws" in the Japanese study, but noted that cell and animal models do not perfectly mimic the situation in humans.

He agreed with the conclusion that BA.2 is "deserving of variant of concern (VOC) status," but said that current monitoring is sufficient and added: "The real experiment is ongoing in the populations of the world and, evidently, disease severity is considerably less than previously."

Mark Harris, a professor at the School of Molecular and Cellular Biology at the University of Leeds in the U.K., told Newsweek the study looked "interesting," but doubted the possibility of extrapolating lab-based data to real-world human infections.

New Coronavirus News from 16 Feb 2022

Research identifies differences between Omicron lineages BA.1 and BA.2 [News-Medical.Net, 16 Feb 2022]

By Jocelyn Solis-Moreira

Early data posted to the preprint server bioRxiv* suggests another Omicron lineage, called BA.2, is more contagious than BA.1 — the Omicron lineage that sparked the winter surge of coronavirus disease 2019 (COVID-19) cases in January 2022.

The current study identified the characteristics of the BA.2 variant and found that compared to the original Omicron strain, BA.2 is more immune resistant and shows greater cell fusion than BA.1.

As of February 2022, the Omicron variant has mutated into three lineages: BA.1, BA.2, and BA.3. A sublineage of BA.1 with an R346K substitution in the spike protein is classified as BA.1.1.

Evolutionary descent of Omicron lineages
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.1 emerged first followed by BA.2 and BA.3. Similar to BA.1 the earlier strains of BA.2, BA.3 and BA1.1 were detected in the Gauteng Province in South Africa suggesting the diversification of Omicron occurred there.

While BA.1 spread across the world at a faster rate than BA.2, the BA.2 lineage became more prevalent than BA.1 since January 2022 in multiple countries, including the Phillippines, India, Denmark, Singapore, Austria, and South Africa.

The study researchers created a model to analyze the epidemic dynamics of different SARS-CoV-2 lineages and estimate the number of COVID-19 cases for each country by each viral lineage. The frequency of BA.2 lineage was 1.40-fold higher than BA.1, suggesting cases caused by BA.2 will expand and spread more rapidly around the world than BA.1.

BA.2 shows resistance to monoclonal antibodies
The genetic sequence in the spike protein of the BA.2 lineage differs considerably from the BA.1 lineage suggesting it may confer greater immune resistance against antibodies.

To study this, the researchers performed neutralization assays with pseudoviruses and neutralizing antibodies that would be produced after vaccination. Results showed that BA.2 was similar to BA.1 in resistant vaccine-induced antibodies. BA.1 has shown to be highly resistant against mRNA vaccines and the AstraZeneca vaccine.

The Omicron BA.2 lineage was also completely resistant to two monoclonal antibodies known as Casirivimab and Imdevimab. Additionally, there was a 35-fold greater resistance to a therapeutic antibody, called Sotrovimab, compared to the B.1.1 virus containing D614G. Both BA.1 and BA.2 were highly resistant to convalescent serum samples containing antibodies after recovery from the original SARS-CoV-2 virus, the Alpha virus, and the Delta virus.

These data suggest that, similar to BA.1, BA.2 is highly resistant to the antisera induced by vaccination and infection with other SARS-CoV-2 variants as well as three antiviral therapeutic antibodies,” wrote the research team.

The researchers also studied convalescent samples infected with BA.1. Thirteen convalescent samples came from fully vaccinated individuals, 1 convalescent sample came from a person with one vaccine dose, and 3 convalescent samples came from unvaccinated individuals. While the results were not statistically significant, BA.2 appeared 1.4-fold more resistant to BA.1-infected sera.

Another observation was that convalescent samples from fully vaccinated individuals showed stronger antiviral effects against all variants compared to the 1-dose or unvaccinated serum samples.

Further investigation showed that BA.1-induced humoral immunity is less effective against BA.2. Using convalescent serum samples from infected hamsters 16 days after infection, the team found both BA.1 and BA.2 showed high resistance against B.1.1 and Delta-infected serum samples. BA.2 showed a 2.9-fold resistance against BA.1-infected convalescent hamster sera compared to BA.1.

Virological characteristics of BA.2 lineage
BA.2 was more contagious than BA.1 when studying the replication process in human nasal epithelial cells. BA.2 also showed significantly more cell fusion than BA.1. There were 1.52-fold larger syncytia seen in BA.2 than BA.1.

The greater fusogenic properties of BA.2 were hypothesized to come from more efficient cleaving of the spike protein than BA.1. However, a Western blot analysis showed the BA.2 spike protein was cleaved less than BA.1’s spike protein, indicating fusogenicity occurred independently of cleavage.

Instead, BA.2 may be more fusogenic and replicative than BA.1 in a TMPRSS2-dependent manner. Cell-based fusion assays revealed the fusogenicity of the BA.2.spike protein and the B.1.1 spike protein was similar in cells containing TMPRSS2 compared to those without it.

*Important notice
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
• Yamasoba D, et al. (2022). Virological characteristics of SARS-CoV-2 BA.2 variant. bioRxiv. doi: https://doi.org/10.1101/2022.02.14.480335 https://www.biorxiv.org/content/10.1101/2022.02.14.480335v1