Transmissibility, severity, reinfection of Omicron BA.2 subvariant

A more contagious subvariant of omicron, known as BA.2, is spreading across the globe and could soon become the dominant version of Covid-19.

It’s now the top variant in at least 18 countries and rapidly spreading, representing 35% of all new cases that have been genetically sequenced worldwide, up from ten countries and 21% of cases the week before, according to new data from the World Health Organization. In the U.S, BA.2 currently makes up 3.8% of genetically sequenced Covid cases, according to the Centers for Disease Control and Prevention.

A pandemic weary public wants to know two main things: Will BA.2 cause a second surge of omicron cases, and will it put even more people in the hospital with severe infections? So far, scientists say the answer to both questions is probably no.

However, Danish scientists confirmed this week that the new subvariant can reinfect people who’ve previously had omicron, although it doesn’t appear to be all that common. They also agree that it’s more contagious than the original version of omicron, BA.1, which is still widely circulating around the world.

But it’s surprisingly not driving a second wave of omicron infections. Globally, Covid cases have plunged 21% over the past week — subsiding in every region except the Western Pacific — while deaths have fallen 8% over the past week, according to data from the WHO.

Maria Van Kerkhove, the WHO’s Covid-19 technical lead, said the global health agency is closely monitoring countries that have detected BA.2, but so far the subvariant hasn’t caused a fresh surge in cases.

“As we’re seeing that decline in cases in countries, we’re not seeing an increase again with BA.2,” Van Kerkhove said during a question-and-answer session livestreamed on the WHO’s social media platforms Tuesday.

Here’s what’s known about the subvariant so far.

Danish researchers have found that BA.2 is about 30% more transmissible than BA.1. Denmark was one of the first countries where BA.2 became dominant, and public health authorities around the world have paid close attention to the situation there to gather insight on what the subvariant might mean for the future course of the pandemic.

“We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1,” a team of scientists affiliated with Danish public health authorities and the University of Copenhagen wrote in a study last month, which has not yet been peer reviewed.

The U.K. Health Security Agency found in late January that BA.2 had a substantial advantage over BA.1 in England. “We now know that BA.2 has an increased growth rate which can be seen in all regions in England,” said Dr. Susan Hopkins, the agency’s chief medical advisor.

“If what is being reported is true that BA.2 is slightly more transmissible, then my strong inclination is to say that BA.2 will likely take over wherever BA.1 was,” said Mehul Suthar, a virologist at Emory University.

However, Suthar said this doesn’t necessarily mean that BA.2 will cause a surge of infection. BA.2’s ability to cause another wave depends, in part, on whether it can reinfect people who have already caught and recovered from omicron, Suthar said.

Danish scientists confirmed on Tuesday that the BA.2 subvariant can reinfect people who previously had its omicron predecessor, BA.1, though the risk of catching the virus again appears low.

The Staten Serum Institute in Copenhagen analyzed a randomly selected sample of 263 reinfection cases. Forty-seven people caught BA.2 less than two months after infection with BA.1, according to the study. The majority of the people reinfected with BA.2 after BA.1 were younger than 20-years-old and unvaccinated.

“The reinfection rate appears to be low given the high number of positive SARS-CoV-2 tests during the study period but still highlights the need for continuous assessment of length of vaccine-induced and/or natural immunity,” the study’s authors wrote.

The people reinfected had mild symptoms and none of them were hospitalized or died. The study also found that people reinfected with BA.2 infection had a reduced viral load, indicating some crossover immunity from the first infection.

The U.K. Health Security Agency, in a separate study, found 69 cases of people reinfected with BA.2 no more than 90 days after their first infection with Covid. However, no instances of people reinfected by BA.2 after first catching BA.1 were found among the 51 cases where enough information was available. The timing of the first infections and sequencing indicated their original Covid cases were the delta variant.

Neither study has been peer reviewed, which is the gold standard in academic publishing. Scientists have been publishing their research as quickly as possible due to the urgency of the pandemic.

The WHO, in a statement Tuesday, said data from early studies of reinfection cases in the general population shows that one infection with BA.1 provides strong protection against reinfection with BA.2.

“It may be that BA.2 has, from its perspective, the unfortunate scenario of coming into a population that has a lot of preexisting immunity that targets it and that may be part of the reason why we’re not seeing it grow as quickly as the BA.1 omicron,” said Andrew Pekosz, a virologist at John Hopkins University.

A large, real-world study in South Africa that also hasn’t yet been peer reviewed found that BA.2 causes illness similar to BA.1 omicron, which generally doesn’t make people as sick as the delta variant. In other words, BA.2 generally does not cause more severe disease.

South Africa’s National Institute for Communicable Diseases found that 3.6% of people who had BA.2 were hospitalized compared with 3.4% of people who had BA.1. About 30% of the patients hospitalized with BA.2 were severely sick compared with 33% of patients hospitalized with BA.1. The study is based on more than 95,000 people who tested for Covid from December through January.

“BA.2 in terms of clinical severity is behaving very similar to BA.1 with a reduced clinical severity compared to previous variants and specifically the delta,” Cheryl Cohen, one of the study’s authors, told a press conference livestreamed on YouTube earlier this month.

WHO officials have repeatedly said there’s no indication BA.2 is more severe. Cohen said the South Africa data is reassuring, but she also cautioned against drawing conclusions about other countries based on the results.

“We should have caution in extrapolating to other places, particularly to other countries where most of the immunity is from vaccination, in contrast to South Africa where most of the immunity is from natural infection,” Cohen said. “Natural infection could potentially provide a more robust protection against BA.1 and BA.2 than vaccinated.”

At least one study found that mutations on the BA.2 spike protein caused more severe lung infection in hamsters than BA.1. The virus uses the spike to invade cells, and the vaccines target that protein to block infection. The team of Japanese scientists who ran the research said the WHO should consider designating BA.2 a separate variant of concern as a result.

Suthar, the virologist at Emory, urged caution when interpreting the results of the Japanese study because it doesn’t use the real version of BA.2. He said mutations on single component of the virus, such as the spike, don’t necessarily determine whether the virus is more severe.

The study hasn’t been peer reviewed and one of the scientists said the results may not hold up in the real world since they used an engineered version of BA.2 to test their theory. The team took BA.2’s spike protein, swapped it out and placed it on the original Wuhan virus, according to Takashi Irie, one of the authors on the study. Irie, in an email to CNBC, acknowledged more reports are showing no increase in severity in BA.2 compared with BA.1.

“Therefore, our study’s finding that BA.2 is more pathogenic than BA.1 may not reflect the actual results of the isolated virus,” Irie wrote. However, he said the study’s results do indicate that mutations on the BA.2 spike are capable of causing more severe infection.

A separate study from Japan, which isolated the BA.2 virus from a traveler who arrived in Japan from India, found that the subvariant had a similar level of severity to BA.1 in mice and hamsters. The study has also not been peer-reviewed.

The WHO’s Covid variant advisory group looked at both the South Africa and Japanese studies, among others, before determining BA.2 should remain classified as omicron rather than designating it a separate variant of concern. This suggests the WHO doesn’t currently view BA.2 as a greater threat to global health than omicron in general.

The original omicron BA.1 strain demonstrated a substantial ability to escape antibodies induced by the vaccines, leading to many breakthrough infections during the recent surge. Danish scientists found that BA.2 is better at evading vaccine protections than BA.1, according to a study published last month.

However, vaccinated people who get breakthrough infections don’t spread the virus as easily to others as the unvaccinated, according to the study. This likely because people who are vaccinated have a lower viral load than people who have not received their shots, the scientists said. In other words, vaccines still help reduce spread of the virus.

Scientists at Beth Israel Deaconess Medical Center in Boston found that BA.2 evades the antibodies from two-doses of Pfizer slightly more than BA.1. Neutralizing antibody levels were about 1.4 times lower against BA.2, according to a study published in early February.

“BA.2 evades antibodies from the Pfizer vaccines similarly to BA.1, maybe slightly more so but not dramatically more so,” said Dan Barouch, an author on the study and principal investigator at Harvard’s Center for Virology and Vaccine Research. Barouch also helped develop Johnson & Johnson’s Covid vaccine.

Barouch said vaccinated people infected with BA.1 also developed robust antibodies against BA.2. “It would suggest that since BA.1 omicron has been very widespread, those people probably have a substantial degree of immunity to BA.2,” he said.

The U.K. Health Security Agency, in a report published Feb. 24, also found the effectiveness of two vaccine doses against symptomatic disease declined to similar levels against BA.1 and BA.2. Booster shots increased protection to 69% against BA.1 and 74% against BA.2 two weeks after the third dose, according to the U.K. study.