CYCLICALLY the variants are making headlines again. In Japan it is the turn of E484K, a mutation found in about 70% of Covid patients hospitalized in Tokyo last month and already present in the South African and Brazilian variants. A high percentage in the midst of a rise in infections in the country that again make fear for the Olympics scheduled in a few months since Japan seems to be at the beginning of a fourth wave. The E484K figure has been released in the media but there are no official statements yet. The good news, however, is that some variants, such as the South African one which contains E484K, appear to be neutralized by mRNA vaccines.
The Japanese variant has not yet been discovered outside the country, but it is certainly the different variants that are taking over the world today.
Eric Topol, one of the most authoritative American scientists, has renamed them “scariants”. A fusion of the words “scare” – which means fear – and “variants”, which means variants. A play on words to point out the excessive alarmism on the viral variants of Sars-Cov-2 in putting out the vaccines against Covid-19. But beware of easy interpretations: the variants must be monitored and how. The English one, for example, increases contagiousness and lethality but is still effectively neutralized by all vaccines in use. And about the evolution of the virus, as he writes on Scientific American Vaughn Cooper – evolutionary biologist from the University of Pittsburgh – the different variants that are emerging would seem to share the same mutations. One more reason to believe in the goodness of the vaccines available.
What is a viral variant?
Any virus, when it multiplies, brings with it “copying” errors in its genetic code. Sars-Cov-2 is no exception. From the first known sequence filed at the beginning of January 2020 to date, there are many mutations that have been created. This is a completely natural phenomenon. The more the virus multiplies, the more it is prone to errors. An example is the flu virus, so changeable in some portions that it has to require an annual update for the success of a vaccine.
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On the Sars-Cov-2 front when these mutations – which occur at a slower rate than the flu virus due to the presence of an enzyme capable of correcting – accumulate over time or in any case when certain particular conditions occur (such as infection in immunocompromised people) it may happen that the virus changes its characteristics to the point of giving rise to a viral variant compared to the original virus. Here because a single mutation, in itself, cannot generate a new variant.
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From the first Sars-Cov-2 sequence to date, hundreds of mutations have accumulated. Being able to sequence the entire genome of the virus – that is to know its “identity card” – it is possible to establish the evolution and geographic spread of the virus. Although most mutations do not have a significant impact, some may give the virus some characteristics such as a selective advantage over others through greater transmissibility, greater pathogenicity with more severe forms of the disease, or the ability to bypass earlier immunity. acquired by an individual either by natural infection or by vaccination.
The role of the English variant
To date, the variants followed with particular interest are the English (B.1.1.7), Brazilian (P.1) and South African (B.1.351) variants. A cause for concern in recent months is the English one, identified at the end of the summer and now predominant in many countries such as, for example, our country. Unfortunately, the English variant has the characteristic of being more contagious due to mutations in the spike protein that improve the link with the ACE2 receptor, which is a way of entry into our body. A considerable problem considering that one of the main problems of the pandemic was the collapse of the health system.
The role of the South African and Brazilian variants
As for the other two more “famous” variants, the South African has been monitored for some time for its ability to evade – at least partially – the immune system response. In this case some modifications in the spike protein would allow the virus not to be best recognized by the presence of antibodies generated after meeting the original virus. The Brazilian one, very similar in composition to the South African, is worrying for the same reasons.
The effectiveness of vaccines
And it is precisely on the effectiveness of vaccinations that research is focusing. A loss of effectiveness would mean making room for the virus again. At the moment, however, this does not seem to be happening. This is primarily due to the “polyclonal” response of our immune system. When the body comes into contact with SARS-Cov-2 – or with a portion of the spike protein in case of vaccination – the defense cells begin to produce different antibodies, each capable of recognizing different portions of the spike protein. According to the most recent studies, at least 5-6 areas of the spike protein could be attacked by the various antibodies. And it is for this reason that some mutations would not be able to modify the characteristics of the protein to such an extent that it is no longer recognized.
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It is no coincidence that the studies carried out to date on Pfizer-BioNTech and Moderna vaccines have confirmed the efficacy, albeit with some differences, against the N501Y and E484K mutations. But the most comforting data is that relating to Israel where the English variant is predominant. In this State, despite the presence of the variant in over 75% of infections, the efficacy of the Pfizer-BioNTech vaccine on the population is completely comparable to that obtained in the trials carried out to get the vaccine approved. But even if other variants were born, the great advantage of mRNA technology is that of being able to produce new vaccines containing the information to neutralize the new mutations.
But be careful to think of the variants as entities in their own right. In reality, for a purely evolutionary matter, the same mutations can be present in different variants. And this is the case with the D614G, N501Y and E484K mutations involving the spike protein.
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The first to be identified is D614G, now present in all B.1 variants of the virus. Discovered already in the first months of the pandemic, this mutation probably confers an advantage in terms of infectivity to the viruses that possess it.
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N501Y has been identified in all three variants that are currently under discussion. This mutation, modifying the conformational characteristics of the spike protein, would make the virus capable of binding with greater affinity to human ACE2 receptors. It is no coincidence that this mutation developed independently in the three variants precisely because it provides the virus with an evolutionary advantage.
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The same goes for E484K too. It emerged independently in different variants, South African and Brazilian in particular, and has recently been isolated also in the English variant. But unlike the previous mutations, which confer greater affinity of the virus to the ACE2 receptor, E484K positioning itself in the most apical part of the spike protein would modify the shape of the protein to the point of reducing its recognition by antibodies both generated by the disease and by vaccination.
Track variants
But to get to update the vaccines against the variants and understand the enemy in front of us, we cannot ignore the sequencing of the virus. Never as in this case is the saying “he who seeks, finds” true. This is why insiders are clamoring for a virological surveillance system to be set up – very similar to that for the flu virus – aimed at tracing the evolution of the virus by characterizing any new acquired characteristics. Useful information both for updating vaccines and for making decisions about containing the virus. It is no coincidence that in the last few hours, in England and Naples, thanks to sequencing, another variant was discovered (B.1.525) which, in addition to containing the E484K mutation of the Brazilian and South African variants, possesses the Q677H mutation. Even if everything will have to be studied in detail, the fear is the possible reduction of the effectiveness of vaccinations.
Precisely because in recent months we have learned that the virus must be anticipated and not chased, it is essential that we invest more in research. To date, it is possible, through a bioinformatics approach, to evaluate the impact on the spike protein of possible new mutations that could arise. Useful information also in this case to better understand the interaction between viruses and humans and to update existing vaccines. And it is always with a view to anticipating the virus that the question of containing the replication of the virus arises. The less Sars-Cov-2 spreads, the less chance it will have of accumulating mutations that could compromise immunity acquired from both natural and vaccine infection. This is why, at present, even those who have received the vaccine must still comply with the rules to prevent any infection. Only by doing scorched earth around the virus will we be able to reduce the risk of new variants. And it is for this reason that the vaccination strategy today more than ever must be global. The virus knows no boundaries.
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