BA.4/BA.5 will soon be dominant in the United States. Here’s what that means

Enlarge / A COVID-19 testing tent stands in Times Square on April 27, 2022 in New York City.

The BA.4 and BA.5 subvariants of the Omicron coronavirus now account for about 35% of cases in the United States, according to the Centers for Disease Control and Prevention. The sub-variants are on track to achieve dominance at a faster rate than the sub-variants before them, including the current sub-variant, BA.2.12.1, which is now in decline.

The pair – who share the same mutations in their SARS-CoV-2 spike proteins but have differences elsewhere in their genomes – are expected to achieve dominance “within weeks,” Dr. Shishi Luo told Ars. Luo is the infectious disease manager at Helix, a California-based population genomics and viral surveillance company that works with the CDC to help track emerging coronavirus variants nationwide.

It is unclear exactly what awaits us in this final phase of the pandemic. What we know about the two subvariants so far is mixed.

Bad and good news

When BA.4 and BA.5 were first detected in South Africa in April, it quickly became clear that both can evade immune responses from vaccination and past infection, even infection with previous variants of the omicron.

On Wednesday, Boston researchers published data in the New England Journal of Medicine that reinforced those findings. The latest data revealed that people who had been vaccinated and boosted had 21 times lower neutralizing antibody titers against BA.4 and BA.5 compared to levels against the original version of SARS-CoV-2. And these levels of neutralizing antibodies were also 3.3 times lower than the levels against BA.1. Similarly, in people who had previously been infected with BA.1 or BA.2 (most of whom had also been vaccinated), the levels of neutralizing antibodies against BA.4 and BA.5 were still almost 3 times lower at levels against BA. .1.

Additionally, 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 is good news so far: hospitalization data from other countries where BA.4 and BA.5 have already increased, including South Africa, suggest that the variants are not causing more serious illnesses and hospitalizations in men.

So, with antivirals still working and vaccination still protecting against serious illness and death, Luo says now is not the time to really worry. “I don’t think it’s necessary,” Luo said of the upcoming wave.

What awaits us

But, as BA.4 and BA.5 approach dominance in the US – making them the fourth and fifth omicron sub-variants to dominate cases this year alone after BA.1, BA.2 and BA.2.12.1 – the question arises: And after?

With BA.4 and BA.5 appearing in South Africa a few weeks ago, we had the opportunity to see this next wave coming. But “at the moment, there doesn’t seem to be any other variants on the rise,” Luo said. There are still virus samples here and there that don’t yet have an assigned lineage – they may be new variants – but none seem to be accelerating, infecting increasing numbers of people, she said. declared. This means that BA.4 and BA.5 could enjoy a longer reign than their predecessors in the absence of promising usurpers.

“But you know, that might change in the next few days,” Luo said. “I wouldn’t let this virus through to mutate again and there be yet another wave.”

Federal regulators and vaccine makers are preparing for the omicron subvariants to be with us at least through the fall and winter. The Food and Drug Administration is preparing to authorize next-generation vaccines and boosters for the fall that could thwart a seasonal surge. The regulator’s expert advisers will meet next week, June 28, to discuss the formulation of these next-generation vaccines. The best candidates are those targeting omicron.

Short and long term plans

On Wednesday, Moderna released preliminary preliminary data that it will present to the FDA, showing that its combination (bivalent) vaccine targeting both the original version of SARS-CoV-2 and the original omicron variant can boost protection against BA.4 and BA.5. Moderna says the bivalent booster, dubbed mRNA-1273.214, can increase levels of neutralizing antibodies against BA.4 and BA.5 up to 6 times.

“As SARS-CoV-2 continues to evolve, we are very encouraged that mRNA-1273.214, our lead knockdown candidate, showed high neutralizing titers against BA subvariants. 4 and BA.5, which represent an emerging threat to global public health,” Moderna CEO Stephane Bancel said in a statement. “We will submit this data to regulators as a matter of urgency and are preparing to provide our reminder next-generation bivalent starting in August, before a potential increase in SARS-CoV-2 infections due to omicron subvariants in early fall.”

While Moderna’s near-term outlook is optimistic, Luo worries about continued viral evolution and our diminishing potential to detect new variants. As people try to get out of the acute phase of the pandemic, people are submitting fewer samples for testing. “Looking forward, we need to determine, will there be [enough samples]? … If not, will there be enough people presenting to emergency care, health systems or hospitals where a sample can be taken and sent for sequencing? I think a system that does this on a large scale doesn’t exist yet,” Luo said.

Although Helix is ​​looking for ways to set up such surveillance systems, Luo says there needs to be a broader national strategy to stay ahead of the variants. While at this time we don’t believe there is another variant on the horizon, it looks like we need a plan for how we as a country will respond to it,” she said. “We can’t keep hoping he’ll go away on his own. In the worst-case scenario where another variant arises that thwarts treatments and vaccines, “we don’t want to go back to square one, do we?” We need a plan.”

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