Omicron coronavirus subvariants BA.4 and BA.5 are now responsible for an estimated 35 percent of U.S. cases, according to the Centers for Disease Control and Prevention. The subvariants are on their way to achieve dominance faster than the subvariants before them, including the current prevailing subvariant, BA.2.12.1, 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 genomes — are expected to achieve dominance “within a few weeks,” says Dr. Shishi Luo vs Ars. Luo is the head of infectious diseases at Helix, a California-based population genomics and viral surveillance company that partners with the CDC to track emerging coronavirus variants across the country.
It is unclear what exactly awaits us in this final phase of the pandemic. What we know so far about the two sub-variants is mixed.
Bad and good news
When BA.4 and BA.5 were first discovered in South Africa in April, it quickly became apparent that the two can evade immune responses from vaccination and previous infections, even infections from previous omicron variants.
On Wednesday, researchers in Boston published data in the New England Journal of Medicine that bolstered those findings. The latest data showed that people who had been vaccinated and boosted had 21-fold lower neutralizing antibody titres against BA.4 and BA.5 compared to levels against the original version of SARS-CoV-2. And those neutralizing antibody levels were also 3.3 times lower compared to levels against BA.1. Similarly, in people previously infected with BA.1 or BA.2 (most of whom had also been vaccinated), the levels of neutralizing antibodies to BA.4 and BA.5 were still nearly three times lower than those to BA. .1.
In addition, a recently published preprint study found that BA.4 and BA.5 appeared to cause more severe disease in hamsters than BA.2 and BA.2.12.1.
But there’s good news so far: hospitalization data from other countries where BA.4 and BA.5 have already skyrocketed, including South Africa, suggest the variants don’t cause more serious illness and hospitalizations in humans.
So with antivirals still effective and vaccination still protecting against serious illness and death, Luo says it’s not time to really worry. “I don’t think that’s necessary,” Luo said of the coming wave.
What awaits us?
But as BA.4 and BA.5 approach 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 looming question on: What’s next?
With BA.4 and BA.5 emerging in South Africa weeks ago, we had a chance to see this next wave coming. But “at the moment there don’t seem to be other variants that are increasing,” Luo said. There are always some virus samples here and there that don’t yet have an assigned lineage — those could be new variants — but none seem to be moving faster and infecting a growing number of people, she said. That means BA.4 and BA.5 could have longer reigns than their predecessors in the absence of emerging usurpers.
“But you know, that could change in the next few days,” Luo said. “I wouldn’t make it past this virus to mutate one more time and another wave to come.”
Federal regulators and vaccine makers are gearing up for omicron subvariants to be with us at least through the fall and winter. The Food and Drug Administration is gearing up to approve next-generation fall vaccines and boosters that could thwart a seasonal surge. Expert advisors to the regulator will meet next week, June 28, to discuss the formulation of those next-generation vaccines. The top candidates are those targeting ommicron.
Planning for the short and long term
On Wednesday, Moderna released preliminary top data that it will present to the FDA showing that the combination vaccine (bivalent) targeting both the original version of SARS-CoV-2 and the original omicron variant provides protection against BA.4 and BA. 5. Moderna says the bivalent booster, called mRNA-1273,214, can increase neutralizing antibody levels against BA.4 and BA.5 up to 6-fold.
“In light of the continued evolution of SARS-CoV-2, we are very encouraged that mRNA-1273,214, our fall lead booster candidate, has shown high neutralizing titers against the BA.4 and BA.5 subvariants , which is an emerging threat to global public health,” Moderna CEO Stéphane Bancel said in a statement. “We will urgently submit this data to regulators and are preparing to deliver our next-generation bivalent booster from August, pending a potential increase in SARS-CoV-2 infections due to ommicron subvariants in early fall. “
While Moderna’s near-term outlook is optimistic, Luo is concerned about ongoing viral evolution and our diminishing potential to detect new variants. As people try to transition from the acute phase of the pandemic, people are submitting fewer samples for testing. “Looking ahead, we have to find out, will there be? [enough samples]† … If not, will there be enough people in the emergency room, health care facilities or hospitals, where there is an opportunity to take a sample and send it in for sequencing? I don’t think a system that does that on a large scale yet exists,” Luo said.
While 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. Even if at this point we don’t think there’s another variant on the horizon, it seems we need a plan for how we as a country are going to respond to it,” she said. In the worst case scenario, another variant emerges that thwarts treatments and vaccines, “We don’t want to go back to square one, do we? We need a plan.”
