• An Omicron variant, known as BA.2 or “stealth” Omicron, is spreading rapidly in some countries, including the United States, United Kingdom, and Denmark.
• A survey of SARS-CoV-2 infections in Danish households has found that BA.2 is more transmissible than the previously dominant Omicron variant, known as BA.1.
• Vaccination provided less protection against BA.2 compared with BA.1, but unvaccinated individuals remained the most vulnerable to infection.
• Compared with BA.1, vaccinated individuals with a BA.2 infection were less likely to pass it on.

Scientists first identified the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, in South Africa in late November 2021.

Mutations in Omicron’s genome have allowed the variant to evade some of the immunity that vaccination or a previous SARS-CoV-2 infection has offered.

Omicron is also more transmissible than previous variants, including Delta, which has allowed it to become the most widespread variant worldwide.

So the news that a more contagious subvariant of Omicron, called BA.2, is spreading rapidly in several countries, including the U.S., the U.K., and Denmark, has raised concerns.

Omicron comprises three distinct evolutionary lineages, called BA.1, BA.2, and BA.3, that split from a common ancestor.

An initial survey of contact tracing data by the UK Health Security Agency, published on January 24, 2022, found that BA.2 appears to be spreading more rapidly in England than BA.1.

This preliminary analysis suggested that vaccines are more effective against BA.2 than against BA.1.

Research in Denmark has now confirmed that BA.2 is more transmissible than BA.1 and that vaccination still protects against infection and onward transmission of the virus.

However, this study found that the degree of protection that vaccines conferred was lower against BA.2 than BA.1.

The research did not provide any evidence about the severity of illness that BA.2 causes.

The study, which has not yet been peer-reviewed, has been published as a preprint on the medRxiv server.

‘Stealth’ variant

By a happy accident, standard polymerase chain reaction (PCR) tests can identify whether someone has an infection with the BA.1 version of Omicron.

The tests work by detecting three of the virus’s genes, including the gene that makes its spike protein.

But the BA.1 version of Omicron has a mutation in its spike gene, so PCR tests only detect two out of their three gene targets. This makes it easy to tell whether someone has an infection with this variant.

BA.2 lacks this particular mutation, meaning PCR tests cannot distinguish it from other common variants.

This has led to health experts dubbing BA.2 the “stealth” Omicron variant because scientists must sequence its genome in order to identify it.

Sequencing samples from people with the infection reveals that BA.2 has been spreading rapidly in Denmark, despite the country’s high vaccination rates.

In the final week of 2021, BA.2 appeared to account for around 20% of all cases of SARS-CoV-2 infections in the country. But by the second week of 2022, around 45% of cases were due to BA.2. This indicates that this subvariant carries an advantage over BA.1 within the vaccinated population of Denmark.

Efficacy of vaccines

Researchers led by the University of Copenhagen wanted to find out whether vaccines still protect people against this subvariant.

Between December 20, 2021, and January 18, 2022, the team monitored 8,541 households in Denmark with a total of 17,945 household members.

Out of a total of 8,541 initial cases of infection in these households during this period, 2,122 were due to BA.2.

During a 1–7 day follow-up period, all the “primary” infections led to a total of 5,702 secondary cases among the 17,945 other individuals who were living in the same households. Secondary cases referred to infections that individuals contracted from the first, or “primary” infections in the household.

The researchers estimate that in households where the primary infection was BA.1, 29% of other household members acquired the virus, while the secondary case rate was 39% for BA.2.

Regardless of whether the initial case was BA.1 or BA.2, unvaccinated housemates were the most susceptible to infection.

However, BA.2 had associations with an increased rate of secondary cases in vaccinated individuals compared with BA.1, meaning that BA.2 caused more infections in vaccinated people than BA.1.

The increase in susceptibility of BA.2 relative to BA.1 was greatest in those who had received a third “booster” vaccination and least in those who had not been vaccinated.

This suggests that BA.2 is better at evading the immune protection that vaccines provide than BA.1. However, as the authors mentioned, “It is likely that this change came with an evolutionary cost for BA.2. To our surprise, we found a decreased transmissibility of BA.2 relative to BA.1 among fully vaccinated and booster vaccinated.”

Compared with BA.1, unvaccinated individuals with a BA.2 infection were more likely to pass on the virus to their housemates.

However, vaccinated individuals with a BA.2 infection were less likely to pass it to their housemates than those with BA.1.

In their paper, the authors write:

“We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1 and that it also possesses immune-evasive properties that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections.”

The biologist and author Carl Zimmer tweeted: “A preprint on BA.2 from Denmark posted on Sunday is in line with Friday’s U.K. findings: it spreads more easily than the BA.1 branch of Omicron, but full vaccination and boosters make it less likely to spread onward.”

Does evolution favor milder variants?

A recent report by the Centers for Disease Control and Prevention (CDC) concludes that while case numbers have surged in the U.S. as a result of Omicron, infections are milder than during previous pandemic peaks.

The Delta variant was also more transmissible but caused less severe disease than previous variants.

This has led many people to conclude that as SARS-CoV-2 evolves to become more transmissible in humans, natural selection will inevitably favor variants that cause less severe or “pathogenic” infection.

However, infectious disease experts say this reasoning is flawed.

“I think the two aren’t necessarily connected,” said Ravindra Gupta, Ph.D., professor of clinical microbiology at the University of Cambridge in the U.K.

Prof. Gupta recently published a study in Nature, which investigated changes in how Omicron BA.1 infects cells compared with the Delta variant.

“There’s no evolutionary reason for a virus to become less pathogenic, at least for this virus, because it’s already transmitted way before it’s made you ill,” Prof. Gupta told MNT.

“It’s an important thing to clarify — people are still not getting it, even scientists and clever doctors,” he added.

Limitations of the study

The authors of the new research from Denmark note some limitations of their study.

In particular, the research period included Christmas 2021 and New Year’s Eve 2021/22, which are public holidays in Denmark.

“Despite government advice to limit social activity, it is likely that there has been considerable social mixing with family and friends outside the households during this period,” they write.

So some of the cases that they labeled secondary cases may, in fact, have been acquired outside household bubbles.

However, they write that this potential bias would apply equally to both BA.1 and BA.2.

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