Here's what we know about the BA.2 Omicron subvariant driving a new COVID-19 wave

BA.2 infections aren’t as mild as once thought and even newer versions of Omicron are circulating and spreading fast

After a brief two-month plateau, COVID-19 cases are rising again in the United States, propelled by the Omicron BA.2 subvariant and its more transmissible descendants. The uptick has experts worried, as more people are shedding their masks and returning to pre-pandemic activities.

Between April 1 and April 24, new COVID-19 cases have jumped by 75 percent, mostly due to BA.2; this subvariant now accounts for almost 75 percent of COVID-19 cases in the U.S. While hospitalizations are still at their lowest levels since the start of the pandemic, they are also trending upward nationally. And COVID-19 cases among nursing home residents and staff are rising again after falling for roughly three months.

“Ongoing transmission of BA.2 is probably related both to the increased transmissibility of the virus together with the reduction of pandemic restrictions,” says Dan Barouch, an immunologist at Harvard Medical School who directs the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center. “Clearly both are contributing to the current surge.”

At the same time, national vaccination rates have stalled out. Only 45.6 percent of the U.S. population has received a booster dose, and in at least 10 states, mostly in the South, more than a third of the population remains unvaccinated. This is especially troublesome because early data suggest BA.2 may cause more severe disease than the original form of Omicron.

The first Omicron wave arrived when many people in the U.S. were already vaccinated, so it seemed to cause less severe illness and got the reputation of being mild, says Ben Cowling, an epidemiologist at the University of Hong Kong. But “mild” was only relative to the very severe disease that previously dominant Delta variant had caused.

Melinda Maldonado, a communications strategist in Toronto, was triple vaccinated when she got a breakthrough infection in December 2021, during the peak of the Omicron wave in Canada. It left her bedridden for weeks, and three months later she still suffers with debilitating fatigue, brain fog, and cognitive disorientation.

“When people say ‘mild,’ they mean you're not dying, like you don't end up in the ICU,” Maldonado says. “For me, this was not mild.”

Now, evidence is building that the BA.2 subvariant is even more infectious than the first form of Omicron, produces more virus particles upon infection, and causes longer-lasting cases of COVID-19.

Why would BA.2 cause more severe disease?

The earlier form of Omicron, called BA.1, was more contagious than previous variants, but it caused less lung damage than Delta because it stayed mostly in the upper airways, says Guowei Wei, a mathematician and molecular biologist at Michigan State University, whose artificial intelligence model had predicted Omicron would be highly infectious. Still, the current crop of vaccines guarded against BA.1, which in most cases caused less severe disease than previous variants among the vaccinated and those who had some immunity from a previous infection.

Studies have shown that the overall risk of severe outcomes from an Omicron infection was lower than it was for Delta. But the risk of hospitalization among children younger than 10 did not significantly differ between Omicron and Delta, and Omicron infections led to a rise in hospital admissions of very young children.

Another study showed that in children, Omicron caused three times as many hospitalizations for respiratory infections compared with prior variants.

Now it seems BA.2 may be even more worrisome. In the U.K. the number of cases being recorded during the current BA.2 surge is much lower than what they saw during the Omicron wave in late December 2021—but the number of hospitalizations is almost equal.

One study that is yet to be peer reviewed suggests why BA.2 might be more severe. A team led by Kei Sato, a virologist at the University of Tokyo, created a synthetic version of BA.2 in the lab, and found that it grows faster in cells lining the nasal passage and has greater propensity to attack the lungs. This BA.2 look-alike virus also caused more severe disease in hamsters than its BA.1 counterpart.

The research suggests that mutations in BA.2’s spike protein—the part of the virus that binds to cells—enable it to dodge antibodies from a previous BA.1 infection.

Another study by Cowling and his team that has not yet been peer reviewed shows that in Hong Kong, the severity of a BA.2 infection is as bad as it was for the original SARS-CoV-2 variant for unvaccinated people of any age.

“In Hong Kong, and right now in Shanghai, I don't think [BA.2] is as mild as maybe people thought,” says Cowling.

Do vaccines still work for BA.2?

Available data show that the currently approved vaccines will prevent severe infection and hospitalization from COVID-19, more so in cases of BA.2 than BA.1.

Both Denmark and South Africa currently have high levels of immunity in their populations stemming from vaccination and infection, respectively. But data from both countries has shown there’s not much difference in severity between BA.2 and BA.1 infections. Reinfection with different subtypes of Omicron is possible, although in highly vaccinated Denmark, it was rare and mainly affected younger unvaccinated individuals.

Booster doses are also showing a lot of promise at protecting people from all forms of Omicron.

Various studies have shown that a third dose of a vaccine, or a breakthrough infection, can rekindle the immunity system’s memory to produce antibodies that work well against all variants, including Omicron. Harvard’s Barouch led a study showing that a third dose of the vaccine is a must for producing sufficient antibody levels against BA.2, just as is required for full protection against BA.1.

The Centers for Disease Control and Prevention (CDC) now recommends a fourth dose of vaccine for people age 50 and older, four months after the third dose; and additional dose for those with compromised immune systems, such as cancer patients. In a study not yet peer reviewed, a fourth dose substantially reduced breakthrough infection among healthcare workers with high exposure risk, even at the peak of the first Omicron wave. In addition, booster doses substantially reduce a person’s chances of transmitting the virus.

By contrast, the Hong Kong study revealed that the outcomes can be severe among unvaccinated people infected with any of the Omicron variants, including BA.2.

More variants on the horizon

As SARS-CoV-2 continues to spread and mutate globally, facilitated by pandemic fatigue, recombinants of variants keep forming; the recently discovered XE subvariant is a hybrid of BA.1 and BA.2 that is starting to spread; XE cases are relatively rare but have grown high enough that the U.K. Health Security Agency estimates it’s about 10 percent more contagious than BA.2.

Meanwhile, a new BA.2 descendent called BA.2.12.1 is spreading even more rapidly, causing 20 percent of all cases in the U.S. within a month of its discovery in early March. Earlier estimates show that BA.2.12.1 spreads faster than earlier strains and could be better at dodging the immune system’s antibodies.

“There are actually many new versions of Omicron, not just two. And in some cases, they do appear to be outcompeting even BA.2,” says Harvard’s Barouch.

This all means the U.S. “needs to recharge its vaccination program” to avoid a likely surge in the fall and winter, says Saad Omer, an epidemiologist who directs the Yale Institute for Global Health in Connecticut.

In addition to vaccines, masks have been shown to be effective in limiting the risk of COVID-19, both by reducing the spread of viral materials from an infected person and by reducing the chances of getting an infection. And avoiding an infection really should be the goal, experts stress: The aftereffects of COVID-19, including the array of symptoms collectively known as long COVID, can be debilitating.

“I thought if I got COVID, it would be the sniffles because that's the predominant narrative,” says Maldonado. “I want people to consider the risk when they think about things opening and not using a mask, because you don't know if it could be you.”

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