A week ago a study was published in Nature in which the researchers described how they closely followed the evolution of the virus in the body of a cancer patient whose immune system was destroyed and discovered mutations that are also able to deal with a large number of antibodies produced against the virus
One of the most important questions these days is whether the corona virus can develop resistance against vaccines. There is no definitive answer yet (and there won't be until it happens), but there are hints. One of them is the case of patient X - a person whose virus ran rampant in his body for 102 days until it killed him. A little over a week ago, an article was published in one of the most respected journals in the scientific community - Nature - about Patient X. The researchers described how they closely followed the evolution of the virus in the body of Patient X, and discovered mutations that are also able to deal with a large number of antibodies produced against the virus.
Or according to the lesson I draw: it is absolutely possible that the virus can develop resistance to vaccines[1].
And an act that was so was.
The patient who never recovered
Before the man at the center of our story became Patient X, he was a man in his seventies. He had cancer in 2012, which along with the drugs he was taking caused his immune system to falter and wane (if the exact terms are of interest to you, he had a severe deficiency of B and T cells).
This situation, in which the immune system does not function, is very dangerous for health. The immune system is supposed to protect us from every tiny invader, and if it is unable to do so, then we can die from any virus, bacteria and fungus - even from diseases that healthy people would recover from within a day or two. It is understandable why there were concerns about Patient X's chances of survival, when he contracted the corona virus and was taken to the hospital.
Then a strange thing happened.
In healthy humans, the immune system fights the corona virus. It may take her a while, but eventually she produces antibodies that paralyze him and sends white blood cells to engulf him. In most people, this is enough to stop the virus. But Patient X's immune system was unable to do any of these, and so the virus ran amok in his body day after day, infecting cell after cell. New cells emerged to replace their predecessors - and these were also infected, destroyed, and in turn replaced by additional cells. It was a battlefield where millions of warriors died every day, and the next day returned to fight again.
The virus had one big advantage: it was able to evolve. Every time the virus infects a cell, it causes the machinery inside the cell to produce large numbers of new viruses. However, from time to time, malfunctions arise in the replication of the genetic code of the virus, and thus new viruses with some mutation are produced.
In normal patients, the virus does not have enough time to undergo significant evolution. The immune system pursues it to the bone and eliminates it within a week or two. The virus has a very difficult time developing mutations that will help it deal with all the different ways in which the body can kill it. But patient X, as mentioned, did not have a functioning immune system, so the virus got its own perfect playground: it could continue to infect cells and mutate. And he did exactly that for 102 long days, during which the patient lay in the hospital on the line between life and death.
The doctors, for their part, did not say desperate. They treated patient X with remdesivir - a drug that has been shown to be useful in the fight against the corona virus[2]. The virus doesn't even blink. And so, having no choice, the doctors provided a plasma donation to the patient.
The miraculous plasma
Plasma is part of the blood fluid - in fact, more than half of the blood volume consists of plasma. It contains various proteins, and perhaps the most important: it contains antibodies that the body has produced.
The plasma that patient X received was taken from people who had recovered from the corona virus, and therefore contained plenty of antibodies against the virus. To clarify: it is not just one type of antibodies, directed against one or two sites to which they can connect on the surface of the virus. That plasma contained a large variety of antibodies that must have attached to the virus in many different ways. This was a real threat to the virus in Patient X's body. If his immune system was still functioning, there is a significant chance that, together with the boost it received from the new antibodies, it could have overcome the virus.
And so, the virus did the only thing it could do. He has evolved.
Evolution against the antibodies
Of course, the virus did not evolve on purpose. This is just figurative language. He didn't get up in the morning and decide to change. It just kept infecting more cells and making offspring of itself. Many of them were captured by the antibodies and failed to infect new cells. Very few - those who underwent mutations that helped them evade the antibodies - managed to continue their harmful activity. They infected new cells, and made more copies of themselves, each of which included the mutations that had helped them so far. And so, in a short time - about 16 days - almost all the viruses in the body contained the beneficial mutation. Then, when the external antibodies wore out and stopped functioning in the patient's body, the frequency of the mutation decreased because it no longer had an advantage.
And what happened when the patient received a new dose of plasma with effective antibodies? True - the frequency of viruses with the mutation jumped again to almost one hundred percent of all viruses in the body.
What is the mutation that helped the viruses to deal with the antibodies? In fact, these are two different mutations. The researchers extracted the mutant viruses from Patient X and grew them in the lab, and thus learned how they benefit the virus. They discovered that the first mutation - named D796H - helped the virus evade antibodies, but impaired its ability to infect. She was not very successful.
The second mutation - delta-H69 / delta-V70 - was almost the opposite in nature: it improved the infectivity of the virus twofold, but did not help it evade antibodies.
Then the two mutants found each other, and the celebration began. When the virus contained both mutations together, it was able to evade the antibodies -=and still=- was endowed with normal infectivity.
It was, in fact, the combination of mutations that doctors all over the world fear: one that is able to deal with all the antibodies in the body better than the original virus, and still be contagious. Most likely, such a mutant virus is also better able to cope with any vaccine, because the vaccines currently accepted against the virus only encourage the creation of some types of antibodies that connect to only one site on the surface of the virus. But the double mutation allowed the virus to effectively deal with all the antibodies that were created against the virus - each and every site - in the bodies of patients who recovered.
And in the end, after 102 days and when the frequency of the double mutation reached almost one hundred percent in the body of patient X, his organs failed and he died.
What are the lessons?
The main lesson the researchers drew from following the evolution of the virus is that one must be careful when donating plasma to patients with a dysfunctional immune system. In these patients, the virus can evolve rapidly, thus creating new and dangerous strains.
The lesson I derive from this study - and it is important to clarify that I am not an immunologist or an epidemiologist - is that the virus is able to undergo mutations that allow it to more easily evade antibodies coming from patients who have acquired immunity against it. It is not able to escape the antibodies completely, but the same combination of mutations described in the article was certainly enough to allow the virus to thrive even under the attack of the antibodies it received.
If this lesson is correct, then we have a big business ahead of us in the coming year. The virus may have undergone a rapid evolution in the body of patient X, but even a slower evolution in the bodies of millions of patients may produce the same dangerous combination of mutations - or perhaps even one that will be even more successful in evading the immune system. From the moment this mutant virus is released to the vaccinated crowd - it will succeed in infecting them.
But - and this is an important but - there is still no certainty that the combination of mutations is really dangerous for ordinary people. Patient X was immunocompromised to begin with. It is possible that normal patients who become infected with the virus with the double mutation will be able to rely on their complete immune system - which does not rely only on antibodies but also on an abundance of white blood cells - to stop the mutant virus.
or not. We just don't know. And yet, it is impossible to ignore the fact that the aforementioned combination of mutations gave the virus resistance to all the antibodies produced by patients, at least in the body of patient X.
As always in biology - and especially in everything that concerns the evolution of viruses and bacteria - we will have to wait and see if the virus will succeed, in billions of different experiments in the bodies of millions of patients, to develop the ability to deal with the immune system and the vaccines effectively.
And in the meantime, one last important point: you should not avoid getting vaccinated just because a mutation may develop that will also deal with the vaccine in the end. In fact, the more people who are vaccinated, the more protected they will be from the variants of the virus that are common today. As a result, the virus will have fewer opportunities to infect them and evolve in their bodies.
Even if that double mutation, or others that give the virus resistance to antibodies, develop somewhere in the world, we will probably be able to prevent its entry into the Holy Land through extremely strict screening of those who land in Israel.
So yes - don't give up on the vaccines. The research currently only provides a hint that someday we may encounter mutant viruses that will also be able to cope with the vaccines, but the cards are still open, the roulette wheel has not yet finished spinning, and nothing is yet certain.
Let's hope for the best, and in the meantime - only health.
[1] https://www.nature.com/articles/s41586-021-03291-y
[2] https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19
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