“There is no room for the emergence of so many other mutations capable of worrying us”, ponders the physician and researcher Jorge Kalil Filho, professor of clinical immunology and allergy at the USP School of Medicine (University of São Paulo) and director of the Laboratory of Immunology from InCor (Heart Institute), in São Paulo.
And he is still referring to space literally. “Perhaps, and it is very likely, we will see the appearance of two or three of these variants that deserve attention, not much more”, predicts the professor, who is highly respected in the international academic world.
Hearing this from your mouth does not mean that things are easy, nor that “two or three” new, more worrying variants ahead cannot do a damn thing. The graphics that Professor Kalil himself showed last week during his class at an event about covid-19 at CAAT – platform online scientific update for health professionals, where it remains recorded – make it clear to anyone that a variant spreads like a fire in a haystack.
In Brazilian regions where most infections had to do with the original virus before, the arrival of one of the new Brazilian strains quickly changed things. The Sars-CoV 2 variants came to dominate the piece, almost with fury. However, to think that it will not be like this indefinitely, if it is not yet to see light at the end of the tunnel, at least it means that, one day, that tunnel may end. Until then…
The antibodies that matter
A virus free and loose in your body is nothing. Every virus, and Sars-CoV 2 is no exception, must be inside a cell. Point. It is there that it reproduces itself and thus its nefarious cycle continues.
Outside, until it gets this den, it can even be stopped by some white blood cells that make up our innate immunity, such as macrophages and monocytes. That, in this case, they only hold the wave of the invader a little, without the slightest chance of stopping him once and for all. They buy time, so to speak. What could stop it before invading a new cell would be neutralizing antibodies. Please keep this adjective – neutralizing.
Now, to enter a cell, by now you must be bald to read and hear, the cause of covid-19 uses a protein, called spike, or simply S. It is the one that gives it a spiky appearance, comparable to a key. The closed cell, in turn, is the ECA 2 receptor.
“But, looking closely, it’s not that protein spike whole that binds to the receiver and, yes, a piece of it, a small place that we call RBD, from English receptor-binding domain or domain of connection to the receiver “, explains the teacher to me, after the event, by phone.
So, moral of the story, the antibodies that matter to us must block exactly that little bit – these, yes, are such neutralizers. “During the infection, even antibodies are produced that bind to other parts of the virus, including other regions of the same S protein, but they are useless. That is, they will not neutralize”, completes the immunologist. If it was a naval battle, it would be a shot in the water. It is the RBD that matters.
The mutations that concern
In the same way, as Professor Kalil tells me, the variants that arouse the interest of scientists always – always, always! – present changes in the RDB. “They are dangerous,” he sums up. “All other variants, in which the virus has changed something here and there outside that piece – and, believe me, hundreds or thousands of them have already happened – are not a concern,” he guarantees.
Now, it is in the RDB that, if the virus exchanges any protein, this may cause it to bind to the receptor faster, unlocking a lighter cell, for example. And that is what, unfortunately, has been happening.
The three variants that matter most
The first to emerge was the British variant around the end of last year. “We are already sure that it is more infectious and, even, that it is much more capable of causing the disease in children”, says Professor Kalil. “The British variant has a change in an amino acid in the RBD and this already causes it to bind even more or has greater affinity with the cell receptor”.
Well, a single different amino acid there in the middle makes the key fit even better in the lock, opening it in a backwards slot. That is why, sometimes, children do not escape. Before, they mostly relied on clinging innate immunity. The virus is now more agile than this defense strategy.
The South African and Brazilian variants also have this change that appeared in the British. But they went further. They have two more very important changes. To complicate matters, the South African variant still took another modified sugar molecule to this altered molecule – and sugar, meddling in this story, interferes a bit with the recognition of antibodies. Everything just seems to get worse.
Our weapons become less efficient
Now imagine – perhaps somewhat simplistically, but validly – that there are several neutralizing antibodies, each fitting into a point on the RDB, preventing it from binding to the receptor on the wall of our cells. “If there is a mutation, however, we have lost a place or two where these antibodies could fit in making the block and perhaps what is over them is not enough to hold the virus,” describes Professor Kalil.
Therefore, antibodies that someone produced because they were infected with the original virus or because they took a vaccine developed before variants appeared may not be as effective. It is, more than ever, expected to have people reinfected. Or that she takes covid-19 after being vaccinated.
Likewise, there are many monoclonal antibodies, created in laboratories from cells of infected individuals – such as what former President Donald Trump received when he was ill – who have lost their role. “Small changes in RDB amino acids already make these antibodies no longer recognize this site”, informs Professor Kalil. “This means that several monoclonals have stopped working.”
The effectiveness of vaccines
There is a correlation between the presence of neutralizing antibodies in the blood and the effectiveness of any vaccine. You may wonder why just a correlation. Simple: because the organism also has another strategy, cellular immunity, which seems to be more important and does not target the virus itself, but destroys the cells infected by it.
However, such cellular immunity is difficult to measure. So, scientists assume that if there are antibodies – something they can test – there is possibly good cellular immunity as well.
And, well, judging only by the antibodies, there is a decrease in the effectiveness of the vaccines in face of the new variants. The virus simply often escapes. In fact, this is how scientists speak: viral escape.
“Studies show that the antibodies produced by vaccines in infections with the original virus managed to neutralize it well”, notes the immunologist. “But in general, they neutralize Brazilian variants up to ten times less. And, if we look at the South African variant, they even neutralize 90% less.”
“Pfizer’s own vaccine efficacy, which in principle offered very high protection, fell considerably with the British variant,” recalls the professor. Say, it seems to plummet even more with the Brazilian variant and terribly more with the South African variant. In fact, this is the sad pattern of all vaccines that have already been tested using samples from patients infected with new strains.
But the doctor makes a point of stressing the following: even with reduced efficiency, vaccines help a lot. “They can stop spreading the disease, but avoid serious conditions, which is already excellent.”
The end of bad surprises
That’s what I heard from the teacher. When asked why, he explained: “Easy to understand: RDB is finite”. In other words, this virus has already changed in three places, in completely different places on the planet, because it brought it a competitive advantage. But they don’t have much more to change in the tiny RDB.
In the same way, scientists can create – indeed, they must create – what they call bridges in current vaccines, just as they do every year with the flu vaccine. It is as if the current version walks up to the changed version. An adaptation. No, immunizations that have proven effective for the original virus should not be returned to square one.
Even so, the main thing is for people to take care of themselves, respect the isolation because each new infection is an opportunity for these bullets that Sars-CoV 2 still has in the cartridge to be used against us, which we are not even aware of the variants that unfortunately are among we. They need less virus to infect someone, infect faster, cause more serious illnesses and kill more as well. One day it ends. When? It depends a lot on us.
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