What do we know about this new variant?

Very little so far. On the one hand, it accumulates a large number of mutations in the spicule, including some that we believe are associated with increased transmissibility and others associated with reduced antibody efficacy. However, as they have never been seen together, we cannot know whether this is really the case or not. Experiments are already being carried out to tell us whether the response to antibodies is similar or not, and in parallel we are looking at its epidemiological growth rate, which will allow us to know whether it has greater or lesser transmissibility than Delta. The fact that for the moment it has been seen growing rapidly in South Africa, displacing Delta, does not necessarily indicate an advantage in transmissibility. We have to wait to see what course it follows in South Africa and, above all, compare with other countries, to see if it makes a niche for itself or not.

For example, Beta was one that we were very concerned about at the time but it never took off beyond South Africa. Therefore, we need to see what trajectory it follows in countries with different epidemiological situations (vaccination, growing or declining cases, etc.). It is true that in South Africa a rapid identification test is being used (genomic sequencing takes some time) and it does seem to be growing at a very fast rate.

Does it deserve special attention in your opinion?

Yes, it does. Not so much because of what we know, which at the moment is little, but because of the potential of the combination of mutations we see. Many of them we have seen in other variants of concern. We must follow it and see whether we are in a scenario like with Delta a few months ago, or it is a false alarm. We must have the ability to identify these potential threats, follow them and assess them. The vast majority come to nothing but some, like Delta, have displaced earlier variants making epidemiological control a little more difficult. In any case, now more than ever, it should be remembered that prevention is based on multiple layers, all of them imperfect but together very good. The best layer we have is vaccines but with Delta we have seen that they do not stop transmission sufficiently. However that does happen when we add masks, distance and ventilation. And that lesson applies to any variant past, present and future.

In light of what is known, could it affect the effectiveness of vaccines?

We don't know yet, we have seen some of the more worrisome mutations in that regard in other variants before, but we also know that it is the combination of all the mutations, how they combine in a particular variant, that determines its behavior. Some mutations in this variant we know that reduce antibody neutralization because we have seen them before. It is not good news, but the immune response also includes the cellular response, which we all have but it is rarely measured because it is not easy. What we do know is that variants carrying some of the mutations reduced effectiveness a little bit but not greatly and there was still good protection against hospitalization and death.

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What is known about this new variant?

The variant has been detected in Botswana this month and is particularly relevant due to the large number of changes in its spicule. It is related to the increase of cases in South Africa, estimating that 90% of the cases detected by PCR in the province of Gauteng may be due to this variant. According to Tulio de Oliveira, director of the Epidemic Response and Innovation Centre in Durban, in less than two weeks it has become the dominant circulating lineage, displacing the Delta variant, which had been the dominant variant in that province until now.

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Does it deserve special attention in your opinion?

The phenotypic characterization of this set of changes in the spicule is very important, since some of them can improve the affinity for the receptor, such as the N440K and S477N changes. Others can have an impact on the activity of neutralizing antibodies, such as the E484A, T478K and Q493K changes. Other can affect the processing of the protein and consequently its transmission, such as the N679K and P681H changes. Therefore, the phenotypic study of this combination of changes is very relevant to know their real impact. Until we have a better set of data, both epidemiological and virological, it would not be very rigorous to make statements about transmission or protection of vaccines, although for those of us who work in surveillance systems, each appearance of a new variant deserves all our attention and work.

In the light of what is known, could it affect the effectiveness of vaccines?

Serological studies are needed to show the impact of this variant on vaccinated persons. Theoretically, this set of changes has the potential to affect the protection conferred by vaccines. In addition, infection with this variant has been described in people vaccinated with a complete regimen by Pfizer, Janssen and Astra Zeneca. The fact is that for the moment the sample studied is small, so we do not have complete information on the matter.

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What is known about this new variant?

It is a variant that appears linked to an outbreak in an area where there was very little virus circulation and with a large unvaccinated population. This variant immediately seems to be growing disproportionately, especially because, being associated with an outbreak, almost all positive cases are related to it and its relative frequency is immediately very high. This apparently makes its growth rate spectacular. On the other hand, and this should not be forgotten, it is true that it has many more mutations than the variants we have seen so far. In the S protein alone, in the spicule, there are already 32 mutations with respect to the original Wuhan virus. Many of these mutations in the spicule, moreover, have been seen in variants of concern and variants of interest previously, but this is the first one that, let's put it this way, brings many, many of them together in a single genome. What is not yet clear, and it will take time to know with reliable and trustworthy data, is whether the accumulation of all these mutations really has the effect of increasing transmissibility, the possible escape to vaccine immunity or to that of the previous infection, or whether it is more virulent and has a worse progress in infected persons. We don't have any data on all that and all we can do at the moment is speculate about it.

Does it deserve special attention in your opinion?

Yes, it deserves attention, but just that: attention. We have to see what happens with it in other environments, and what happens if it reaches other countries. For that we have to be vigilant, but it is one thing to be vigilant and another thing to alarm. It does not seem that the situation requires an alarm, but a similar vigilance to that which was previously carried out with the rest of the variants. Vaccines continue to have the high effectiveness they have. We have seen that over time the effectiveness of the vaccines decreases, hence the booster doses, and it is not expected that this variant will be any different.

In the light of what is known, could it affect the effectiveness of the vaccines?

With what we know, we have no evidence that it could affect it. We know that it has some mutations that decrease the neutralizing capacity of specific antibodies, but vaccines trigger the production not of a single antibody, but of many antibodies (possibly dozens of them). It does not appear that this virus has the ability to simultaneously evade all the antibodies that are produced when a person is vaccinated. Decrease, yes, but not such that we have to think that there will be an increase in persons infected with this variant despite being vaccinated, and getting critically ill. We should be vigilant to take the necessary measures if this occurs, such as revaccination or make a new vaccine formulation to correct this undesirable deviation.

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It is still too early to make any assessment of this new variant of the B.1.1.529 lineage. It is true that it has many mutations in the spicule protein that have been found in other variants of interest and concern, such as the Alpha and Delta variants, associated in some studies with a possible increased transmission capacity and a possible different response to neutralizing antibodies, but we must await surveillance and more data. The ECDC already recognizes this variant as a variant of interest while waiting to assess its designation as a variant of concern based on its epidemiological impact in the European Union.

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