What We Know About Fast-Spreading Omicron Subvariant BA.2

(Bloomberg Opinion) -- Viruses mutate. So it came as little surprise that the fast-spreading omicron variant (known as BA.1) has a faster-spreading subvariant, BA.2. The latter is becoming dominant in Denmark, increasing in the U.K. and quickly spreading elsewhere. New studies show that getting a mild omicron infection may not give a robust enough immune response to protect against another omicron infection, of either BA.1 or BA.2.

Bloomberg Opinion columnist Therese Raphael speaks to Bloomberg Intelligence Pharmaceutical analyst Sam Fazeli about what BA.2 means for living with the virus.

Therese Raphael: If BA.2 is taking over from the original omicron, does that mean it’s more transmissible? And does that suggest it can better evade our immune responses?

Sam Fazeli: What is interesting is that BA.2 (and another subvariant, BA.3) was discovered early on in South Africa when omicron was first described. But, as viral spread is not just about how infectious a virus is, BA.1 became dominant. Now it’s clear that BA.2 has a fitness advantage over BA.1, with household transmission data from Denmark suggesting one-third higher transmissibility vs. BA.1, in line with U.K. data showing about 30%. Why it is taking over BA.1 is not clear, but you are seeing a similar trend in other countries. This won’t be helped by booster shots given three or four months ago, given that both subvariants are adept at escaping immunity.

As such, the decline in cases in countries where BA.2 is taking over may be slower than it could have been, potentially creating a smoldering background of infections at relatively high levels. This could in turn lead to higher hospitalizations, especially in countries with lower vaccination rates.

TR: We know viruses change so they can survive. How exactly is BA.2 different from the original omicron?

SF: BA.2 differs by about 40 mutations compared with BA.1. The spike protein of BA.2 — the rod-like protrusion the virus uses to attach to and infect human cells — has fewer amino-acid changes, with 27 vs. 31 for BA.1. These have the potential to change the function of its proteins. So while BA.2 is related to BA.1, there are enough differences to drive a change in the behavior of the virus.

The other key differences as regards the spike protein are that BA.2 has regained some deletions of certain amino-acids. These may actually make the virus more susceptible to neutralization by antibodies, but this has not been studied in the context of omicron.

TR: I think the main question people wonder with a new variant is whether there is any compromise in the effectiveness of vaccines. What are we seeing with BA.2?

SF: What has not changed about omicron, whether BA.1 or 2 or some other subvariant, is its ability to evade the immunity induced by vaccines in terms of preventing an infection. U.K. data shows that the vaccine effectiveness of a third shot of the vaccine is about 70% against BA.2 vs. 63% against BA.1, two weeks after the booster shot. This level will likely fall over time. But protection against an infection 25 weeks after the second shot was a dismal 9% to 13%. Still, this apparent fall in vaccine effectiveness is likely to be at least partly the effect of rising immunity in the unvaccinated population due to natural infection.

Also, the critical thing about vaccines is protection against severe disease, which is still maintained at a much higher level than against omicron.

A key question for me is whether a BA.1 infection provides protection against BA.2 and vice versa. I expect this to be the case, but getting some data would be good. It would suggest that the omicron-specific vaccine being developed by Pfizer Inc.-BioNTech SE and Moderna Inc. should have utility even if BA.2 has taken over.

TR: Are we seeing any greater severity in the BA.2 infections? And is there any difference between natural and vaccine-given immunity in fighting off BA.2 infections?

SF: I think the best way to assess this is by comparing what is going on in Denmark to the U.K. The two countries have similarly high levels of vaccinations as well as booster doses. The characteristics of their respective populations are also relatively similar. So looking at the rate of hospitalization and ICU admissions in Denmark should help in assessing the severity of BA.2 — which accounted for 57% of cases in Denmark as of Jan. 24. We find very little difference compared with the U.K., where BA.1 is still most prominent, in terms of ICU admissions relative to the number of cases.

TR: How are we tracking new variants and subvariants?

SF: Because BA.2 regained some of the genetic deletions that BA.1 carried, it is not distinguishable from delta by simple PCR analysis. As such, the only way to properly track which omicron sub-variants are predominant is to use full genomic sequencing, something that Denmark, the U.K. and South Africa, just to name a few, excel at, but which the U.S. does much less.

TR: We have now seen a number of different variants and subvariants through this pandemic. Does the direction of travel and virology generally tell us anything about what we might expect in the future, assuming that BA.2 isn’t the end of the road for SARS-CoV-2?

SF: I am wondering the same thing. Is it possible that an infection by, say, delta followed by omicron a few months later, or vaccination with one of the current vaccines followed by an omicron-specific shot, provides broad enough immunity to protect against most current and potential future variants? Is it possible that the virus has now tried and tested the main mutations that help it infect better and/or escape immunity without compromising its fitness? Or does it still have a lot of “evolutionary space” left to explore? These are the questions we can’t yet answer.

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• Why An Omicron-Specific Vaccine Is Worth Testing: Therese Raphael and Sam Fazeli

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Therese Raphael is a columnist for Bloomberg Opinion. She was editorial page editor of the Wall Street Journal Europe.

Sam Fazeli is senior pharmaceuticals analyst for Bloomberg Intelligence and director of research for EMEA.

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