Three sub-variants of the Omicron variant are currently circulating in Europe: BA1, which arrived at the end of November and was responsible for the first Omicron wave; BA2, which has become dominant in Denmark and may be responsible for the recent explosion of cases; and BA3, which is less infectious and is far from prevalant.
BA2 is the focus of concern. While information on its characteristics is lacking at the moment, the impression is that it could, because of its potential for greater contagiousness, surpass BA1 and become dominant in Europe. That is the opinion of researcher Danielle Perez-Bercoff, a virologist at the Luxembourg Institute of Health (LIH).
But it is difficult to say for the moment whether BA2 is more pathogenic than BA1 and therefore whether it can have an impact on the number of hospitalizations. It seems it will take another 10 to 15 days to gather sufficient information. It is also likely that the protection provided by current vaccines will continue to be effective against possible severe forms. In any case, the medical community seems to be betting that it is not more virulent, with European governments gradually lifting health measures despite the unknown.
The sub-variants of the Omicron variant seem to be the focus of concern. Which ones are circulating in Europe?
Danielle Perez-Bercoff: There are three sub-variants, named BA1, BA2 and BA3. BA1 arrived in Europe at the end of November. At the time, we neglected to look at BA2, which arrived in Europe at about the same time in some countries.
How do these sub-variants differ from each other?
BA1, BA2 and BA3 have several mutations in common. BA1 and BA2 have, in addition, their specific mutations. And BA3 is in between: it takes mutations from BA1 and BA2, but it has no mutations of its own.
BA3, for some reason, is not very transmissible. It is dwarfed by the others and accounts for a tiny proportion - 0.013% - of infectious cases. BA1 and BA2 are much more infectious than Delta. That's why they dominate in Europe, but also in the US, India, Africa, etc.
The impression is that the BA2 sub-variant will take over from BA1.
The BA1 sub-variant dominated the first wave of Omicron in Europe. But since then, BA2 has taken over in some countries, like Denmark, where it has become dominant. Is this likely to become more widespread in Europe?
The impression is that BA2 will overtake BA1. Why didn't it do so in the first place? Probably because BA1 was introduced first in some countries and, because it is more infectious than Delta, it has replaced it.
In other countries, where both were probably introduced at almost the same time, BA2 has taken over. We have the impression that this is what will happen all over Europe.
Does BA2 cause more severe forms than BA1?
It is very difficult to say. At the moment, we don't know if BA2 is as pathogenic as BA1 or how sensitive it is to antibodies. These answers will come in 10 or 15 days.
The virus is evolving faster than we are developing vaccines. So we are running behind.
Regarding BA1, which we have worked on the most so far, we tend to say that it is less pathogenic than Delta. This is probably true. One of the reasons is that it doesn't infect the lower lung tract, but the upper respiratory tract, which changes a lot in terms of respiratory distress.
But the general population is also much more immune, either through vaccination or by infection, than in the Delta wave. So the immune response already pre-exists in a large majority of cases.
Is BA2 resistant to vaccines?
At the moment we don't know for sure. What we are seeing is that the virus is evolving faster than we are developing vaccines. So we're running behind.
But giving booster doses with the original virus, while not 100% protective, is effective against severe forms of the disease, although not optimal against transmission.
So will BA2 be totally resistant to the vaccines we have today? I'm not sure. But even if you are moderately protected against transmission, I think the vaccine will still be effective against the severe forms.
I think the vaccine will remain effective against the severe forms.
Why is that?
Antibodies, which protect against infections, are the most sensitive to mutations. But Omicron is full of mutations that allow it to escape the antibodies. So even if you have a high level of antibodies, these mutations allow it to hide from them.
In contrast, the cellular response, which will kill the infected cells and thus prevent the virus from multiplying, is much more effective against a large number of variants because it recognises parts of the virus that are not affected by the mutations. This form of immune response takes longer and is difficult to measure, but it is much more effective against variants.
There seem to be difficulties in detecting BA2...
When the Omicron BA1 wave arrived, we were able to distinguish between the Omicron and Delta variants very quickly, because one of the mutations in BA1 is a deletion that does not allow the spike gene to be caught in diagnostic tests. We were thus able to follow the implantation of Omicron without having to sequence everything.
All countries are lifting their health measures. It's a gamble.
But BA2 does not have this deletion. Distinguishing between Delta and BA2 is therefore more complicated because you have to sequence everything or look for other points of mutations to find out whether it's Delta, BA2 or something else.
Why is detecting BA2 so important?
We need to be able to detect and distinguish this virus, especially if we find that it differs slightly in terms of pathogenicity or sensitivity to treatment. If that's the case, we need to know what we're dealing with so that we can adjust treatment in the hospital accordingly.
Denmark, where BA2 is dominant, is experiencing an explosion of cases. But the intensive care units are emptying. So they have lifted the last restrictions. Is this political decision premature?
It's the same everywhere, all countries are lifting their health measures. It's a gamble. Two aspects are important. On the one hand, people are vaccinated. On the other hand, Omicron is intrinsically a little less pathogenic than Delta. So having global immunity at the population level, either through Omicron or through vaccination, solves a lot of problems for the next few months. Immunity doesn't last forever, but some of it stays in memory. So it's a matter of getting to the summer.
We have no guarantee that the next variants will be derivatives of Omicron.
Should we be worried about the BA2 sub-variant?
As much as with BA1. My impression is that doctors are no more worried about BA2 than BA1. There was a lot of concern when BA1 exploded: it was going so fast, it was so infectious and we didn't know if it was less pathogenic. But in the end the hospitals did not fill up. For BA2, I think the medical community is betting that it's similar to BA1. But the data is not there yet.
We hear a lot that the less pathogenic Omicron variant is a turning point in the pandemic, because the next variants will now be less pathogenic in general. What do you think?
It's very possible, but there are no guarantees. The point of a virus is to transmit itself as well as possible, not to kill the host, because then it will just die out with the host.
But we have no guarantee that the next variants will be derivatives of Omicron. Before Omicron, we thought the next variants would be a derivative of a variant we knew, and Omicron came out of nowhere, from another branch. So there's no guarantee that there isn't another variant brewing somewhere whose pathogenicity we do not yet know.
The epidemic is difficult to predict because you don't know where the next variant is going to emerge from.
In addition, there are several variants circulating: BA1, BA2, BA3, Delta, as well as old variants such as Alpha or Beta... Now, if a person gets infected with two variants simultaneously, you don't know what comes out. It could be a non-viable virus that won't spread, or it could be a so-called recombinant variant with the same pathogenicity as Omicron, but better transmissibility. Or, and this is the worst case scenario, it is as transmissible as Omicron and as pathogenic as Delta.
So the epidemic is difficult to predict because you don't know where the next variant is going to emerge from. Other variants will emerge anyway. The question is whether they will be derivatives of Omicron or new variants.