Why is it so difficult to know if new variants of SARS-CoV-2 are more contagious?

The SARS-CoV-2 variant identified in the UK (B.1.1.7) was first identified in a virus isolated from a patient on September 20, 2020, but did not initially raise any suspicions. By mid-November it was already present in 26% of cases. In the week of December 9, in 60% of sequenced patient samples in London. Today it is dominant in the country and is present in another 70.

In late 2020, the South African Genomic Surveillance Network identified the 501Y.V2 variant. It seems that it can spread better between people compared to others, and it may also be able to partially evade the antibodies generated by a previous infection or the vaccine. Today it is present in more than 40 countries.

In January 2021, variant P.1 was identified for the first time in travelers from Brazil arriving in Japan. This has mutations that, like what happens with the one identified in South Africa, could affect the ability of the antibodies generated, either by natural infection or by vaccination, to recognize and neutralize the virus.

These data are worrying and make us suspect that these variants may have an important effect on the way the virus infects, either by increasing its transmission, infectivity or bypassing our immune system. However, why is it only about suspicions and it is not clearly stated whether these variants are dangerous or not? Why do they take so long to say something that seems so obvious?

The answer is that it is not said because it really is not clearly known. It is true that science does not always go as fast as we would like, but it is important to note that just because something may seem obvious does not mean that it is true. Before affirming something, you have to check it.

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So far the only thing we have is epidemiological data where the growth in the number of cases infected with each variant within the same population is compared. That’s where the headlines come from saying that “the UK variant could be up to 70% more contagious.”

However, although with these data we can very clearly suspect that some of these variants could be better transmitted, nothing can be concluded because they are only estimates. Those percentages could be due to other reasons. For example, to events of super spread Or that these variants simply grow a little better than the previous ones and that is why they have been imposed so clearly.

An example of a super spread event could be an individual infected with a new variant who goes to a party or a concert where he does not use preventive measures, or simply has a great social life and ignores the recommendations.

On the other hand, an example of a mutation that gives the virus a certain advantage but does not necessarily make it transmit better is the mutation. D614G. This appeared in Europe in February 2020 and ended up prevailing in the rest of the world in a few months. So far, there is some evidence in the laboratory that viruses with this mutation could be transmitted better, but it is not entirely clear.


Korber et al / Cell

How then is it explained that there are so many cases? It can happen that a virus grows better than others in cells, and that is why its sequence is imposed. However, this does not always mean that you have to increase your transmission.

Therefore, although everything indicates that these variants may be more transmissible than the previous ones, in order to really conclude something, controlled experiments must be carried out in the laboratory. This requires time and solving certain problems that appear.

The challenge of studying variants in the laboratory

The first thing to do is see how the new variants grow in cell culture compared to the old ones. However, this presents a big problem because the virus, in addition to mutating when it infects people, it also mutates in the laboratory.

The laboratories send us a tube with a little of these viruses. In order to study them, you must first grow them in cells until you have enough to do experiments. The problem is that when they multiply, they usually acquire mutations in certain regions of their genome.

In general, the part of the virus that mutates the most when replicating in the laboratory is protein S (the key that the virus uses to enter the cell), which is also the area where most of the new variants have incorporated the mutations more interesting.


@microbioblog

Therefore, it is not as easy as having the virus and doing experiments. First you have to grow it in sufficient quantities and make sure, at each step, that you keep the original mutations and that you have not incorporated new ones.

Once we have the virus and have seen how it grows, the next thing is to do experiments to study its transmission in comparison with other variants. For this, animal models are used, such as ferrets.

In these experiments, animals are infected and placed in cells with other uninfected animals to see if there is direct transmission or not. In addition, animals are placed in other cells to assess indirect transmission.


Wikipedia

In addition, it must be taken into account that the effect of the different mutations can go far beyond increasing the transmissibility of the virus or its lethality. For example, a recent and very preliminary (pending peer review) suggests that infection with the variant identified in the UK might last longer compared to previous variants and thus escape of quarantines. According to this hypothesis, which will require more studies to corroborate or discard it, a solution could be to lengthen these periods.

Lack time to experiment

In summary, to really conclude if these new variants are more contagious or not, a certain number of experiments must be carried out in the laboratory and solved certain problems that appear, which requires a certain time.

Finally, it is important to note that, although there is no conclusive evidence that these new variants are more transmissible or lethal than the previous ones, it is clear that something do. They represent a real problem to be faced.

Therefore, in cases like these, where the suspicion of further transmission is quite high, it is important to make decisions, even in a preventive way, and to reinforce measures to avoid greater evils.

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