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Omicron coronavirus subvariants BA.4 and BA.5 now account for an estimated 35 percent of U.S. cases, according to the Centers for Disease Control and Prevention. The subvariants are on track to achieve dominance faster than the subvariants before them, including the currently reigning BA.2.12.1 subvariant, which is now in decline.
The pair – which share the same mutations in their SARS-CoV-2 spike proteins but have differences elsewhere in their genome – are expected to achieve dominance “in a matter of weeks,” says Dr. Shishi Luo to Ars. Luo is the chief of infectious diseases at Helix, a California-based population genomics and virus surveillance company that works with the CDC to track emerging coronavirus variants nationwide.
It is unclear what exactly lies ahead in this final phase of the pandemic. What we know so far about the two subvariants is mixed.
Bad news and good news
When BA.4 and BA.5 were first discovered in South Africa in April, it quickly became clear that the two immune responses could evade vaccination and previous infections, even infections from previous Omicron variants.
On Wednesday, researchers in Boston published data supporting these findings in the New England Journal of Medicine. The latest data revealed that individuals who had been vaccinated and boosted had 21-fold lower neutralizing antibody titers against BA.4 and BA.5 than levels against the original version of SARS-CoV-2. And these neutralizing antibody levels were also 3.3-fold lower compared to the levels against BA.1. Likewise, in individuals previously infected with BA.1 or BA.2 (most of whom had also been vaccinated), neutralizing antibody levels against BA.4 and BA.5 were still nearly 3-fold lower than levels against BA .1.
In addition, a recently published preprint study found that BA.4 and BA.5 appear to cause more severe disease in hamsters than BA.2 and BA.2.12.1.
So far, however, there is some good news: hospitalization data from other countries where BA.4 and BA.5 have already surged – including South Africa – suggest the variants are not causing more serious disease and hospitalization in humans.
With antivirals still effective and vaccinations still protecting against serious illness and death, Luo said it’s not the time to really worry. “I don’t think it’s necessary,” Luo said of the coming wave.
what’s ahead
But as BA.4 and BA.5 are nearing dominance in the US – making them the fourth and fifth omicron subvariants to dominate cases this year alone, after BA.1, BA.2 and BA.2.12.1 – the question arises: what comes next?
When BA.4 and BA.5 showed up in South Africa weeks ago, we had a chance to see this next wave coming. But “at the moment, there doesn’t seem to be any other variants that are going up,” Luo said. There are always some virus samples here and there that don’t yet have an assigned lineage – these may be new variants – but none seem to be picking up speed and infecting growing numbers of people, she said. This means that BA.4 and BA.5 could enjoy longer reigns than their predecessors in the absence of aspiring usurpers.
“But you know, that could change in the next few days,” Luo said. “I wouldn’t expect this virus to mutate again and have another wave.”
Federal agencies and vaccine manufacturers are gearing up for omicron subvariants to be with us at least through the fall and winter. The Food and Drug Administration is preparing to approve next-generation vaccines and booster vaccines for the fall that could thwart a seasonal surge. Expert advisers from the regulator will meet next week, June 28, to discuss the formulation of these next-generation vaccines. The top candidates are those targeting omicron.
Short and long term plans
On Wednesday, Moderna released interim top-line data it will submit to the FDA showing its combined (bivalent) vaccine targeting both the original version of SARS-CoV-2 and the original Omicron variant , which can increase protection against BA.4 and BA.5. According to Moderna, the bivalent booster, dubbed mRNA-1273.214, can increase neutralizing antibody levels against BA.4 and BA.5 by up to 6-fold.
“Given the continued evolution of SARS-CoV-2, we are very encouraged that mRNA-1273.214, our lead fall booster candidate, has demonstrated high neutralizing titers against subvariants BA.4 and BA.5, which pose an emerging threat to the global public health,” said Stéphane Bancel, CEO of Moderna, in a statement. “We are providing this data to regulators as a matter of urgency and are preparing to deliver our next-generation bivalent booster starting in August, ahead of a potential spike in the early fall SARS-CoV-2 infections due to omicron subvariants is possible.”
While Moderna’s near-term outlook is optimistic, Luo is concerned about ongoing viral development and our diminishing potential to spot new variants. As people try to get out of the acute phase of the pandemic, people are submitting fewer samples for testing. “Looking ahead, we need to find out if there will be one [enough samples]? … If not, will there be enough people presenting themselves in emergency care, health systems or hospitals where there is an opportunity to take a sample and send it for sequencing? I think a system that does this on a large scale doesn’t exist yet,” said Luo.
Though Helix is exploring ways to set up such surveillance systems, Luo says there needs to be a broader national strategy to stay ahead of variants. While we don’t think there’s another variant on the horizon right now, it seems we need a plan for how we’re going to respond as a country,” she said. “We can’t just hope it goes away on its own.” In a worst-case scenario, where another variant emerges that thwarts treatments and vaccines, “we don’t want to go back to the beginning, right? We need a plan.”
