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How Worried Should We Be About the BA.2 Omicron Subvariant?

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A subvariant of Omicron known as BA.2 has taken over as the dominant COVID strain in several countries, including the Netherlands and South Africa, and is expected to pass Omicron classic, known as BA.1, in the coming weeks in India and the Philippines. While the rise of another strain has some Americans stressed over the prospect of yet another wave of cases, it may not be time to panic just yet. Below is a conversation with Dr. Dan Barouch, a Harvard Medical School professor and the leading author on a preprint study on immune-system response to the BA.1 and BA.2 strains. Barouch, who led design efforts in the development of the Johnson & Johnson vaccine, says that while it’s “very likely” that BA.2 will gain momentum in the U.S., there’s no guarantee of a massive surge in cases like with its close cousin.

Simply put, how concerned should we be about the spread of BA.2 in the United States?
I guess it’s worth asking whether one of these Omicron subvariants is likely going to grow and become more common in the United States. I think that is very likely, that the Omicron subvariant BA.2 will continue to gain ground and possibly even replace the current virus population, though that remains to be determined.

It also remains to be seen whether this variant is fundamentally different in terms of what matters to patients, which is: Is it more transmissible, is it more severe, and does it escape vaccines?

Let’s look at those three, then.
For transmissibility, it does appear to be gaining ground in a population in which there’s a lot of Omicron virus circulating. So it does appear to be more transmissible. Does it result in a more severe illness? I think the jury’s out on that. I’m not aware of any clinical data that shows it’s more severe. Where it’s taken over as the dominant variant, like in South Africa, it doesn’t appear to be causing the same sort of hospitalization and death rate that Delta caused a number of months ago. So I would say that it’s not clear that it’s more severe and so far it looks like it’s clinically, relatively similar, but there’s very little information.

There was a preprint that came out this week in Japan suggesting that BA.2 could be more severe, but it was done in hamsters.
When I say clinical data I’m specifically referring to humans. Population studies of humans. I’m aware of the preprint from Japan and the laboratory model and animal models have some limitations to them. For example, Omicron BA.1 is actually very mild in hamsters. But I would argue that human clinical data is probably the most relevant here.

Fair enough. But how effective does BA.2 appear to be at escaping vaccines?
In our preprint, which is under review at a major journal, we looked at Pfizer-vaccinated individuals as well as a cohort of Omicron-infected individuals. Similar to with BA.1, there was very little neutralization prior to a third boost of Pfizer. But after a third boost, neutralizing antibody titers [a test that measures the level of antibodies in a blood sample] came up strongly to both BA.1 and BA.2, still at substantially lower levels than the vaccine-matched strain. The neutralization titers between BA.1 and BA.2 were relatively similar. In our hands, there’s a slight trend toward lowering antibody titers against BA.2 about 1.3-to-1.4-fold.

That’s a relatively minor difference; overall, we found that antibody responses to BA.2 were roughly comparable, trending slightly lower, but roughly comparable to BA.1. That was true in vaccinated individuals and in people who were infected with Omicron BA.1. Those two data sets suggest that Omicron BA.2 does evade vaccines but to a similar extent, not a greater extent as Omicron BA.1. Also it shows that people who are vaccinated and then infected with BA.1 have high neutralizing antibody titers against BA.2, suggesting there would be a substantial degree of cross-reactive natural immunity as well.

Could you explain what makes BA.2 more transmissible?
I can’t because I don’t know. There are a lot of mutations that are similar between BA.1 and BA.2, but each one has a lot of separate mutations and the biology of each one of those mutations is not yet fully known. So I don’t believe we know exactly why BA.2 appears to be more transmissible than BA.1. It does make sense that there’s so many mutations on BA.1 that it may not be optimized for human transmission. It makes sense that when something fundamentally different arrives, there might be further iterations that make it more adaptive to human populations. So I’m not surprised that there’s variants and subvariants of Omicron that are slightly or somewhat better in different regards. This one, according to our data, appears to have relatively similar immunological properties to BA.1.

So does that assuage any fears of another massive wave like with Omicron 1.0?
I can’t predict whether it will be a new surge or not, but it’s probably going to be driven more by increased transmissibility. It has similar, not fundamentally greater, ability to evade vaccines. The ability of BA.2 to become more dominant than BA.1 in certain populations appears to be more due to its increased transmissibility rather than some sort of brand-new immune escape from vaccines.

What do you think about the decision to drop mask mandates in New York and California just as BA.2 appears to be making inroads?
Overall, the Omicron surge is coming down. We’ll have to monitor very closely whether one of these subvariants will lead to an uptick in infections. I do agree that what’s most important is hospitalizations and deaths; the case numbers are not as important as the numbers of severally ill people. But I think that people are weary, people have pandemic fatigue, it’s definitely going in a better direction now than it was a couple months ago. But we have to be vigilant with testing and making sure that as we start to roll back pandemic restrictions, we don’t see a new surge in cases, particularly not severe cases.

It’s the next chapter of the pandemic. It’s probably not a completely different chapter; it’s probably a subsection of the Omicron chapter.

How Worried Should We Be About the BA.2 Omicron Subvariant?