Omicron represented a “leap” in the history of the virus, but in reality it came as no surprise to the experts. Perno (Child Jesus): “It is not excluded that a new variant may arise, but it should be more ‘perfect’ than the current one”
What will come after Omicron? The possibilities are many, the certainties few. Given that no one believes anymore in the hypothesis of the disappearance of the virus, the macro scenarios are two: Covid is reduced to something similar to seasonal flu, or a new variant, even more “perfect” than Omicron, appears. That is, with a greater ability to transmit and replicate, combined with a significant degree of immune escape.
If “Pi” (in theory it should be called that) also turns out to be a carrier of a more serious disease, this could be the worst option. Several experts around the world are wondering what will happen in the coming weeks or months. Second an analysis recently published in Nature
the pandemic has not slowed the pace, despite the relatively mild infections caused by Omicron and the very high levels of immunity of the population around the world.
The authors – from the University of Oxford and the European Joint Research Center of Ispra (Varese) – argue that the rapid evolution of the virus still underway can lead to the birth of new variants, potentially capable of escaping immunity and triggering a more serious disease than the previous ones. With a metaphor, we could say that Sars-Cov-2 is “armed to the teeth”: it has on its side the very high transmission capacity, the gradual decline of immunity given by vaccines or infection and a series of potential reservoirs animals.
In addition, the authors of the study point out Nature, the lower virulence of Omicron should not deceive: in a virus, while the immune escape and transmissibility are under strong evolutionary pressure, the ability to cause more or less serious disease derives from complex interactions between factors both in the host and in the pathogen. «Viruses evolve to maximize their transmissibility and at times this can be related to greater virulence – they write -. The prospect of future variants with the potentially disastrous combination of the ability to reinfect due to immune leak together with high virulence is unfortunately very real ». Sars-CoV-2 is characterized by a significant antigenic evolution, i.e. a continuous modification of the viral profile in response to the host’s immune pressures. Hence the immune leak, that is, a reduced ability of the immune system to prevent reinfection (exactly what is occurring with Omicron) and the consequent potentially serious illness.
Omicron – the scholars underline – has at least 50 amino acid mutations with respect to the ancestral reference strain (Wuhan) and is also very different from the previous variants. Its explosive spread in populations with high immunity shows how mutations make it possible to easily infect individuals with immunity due to previous infections or vaccinations. Not only. There are also considerable genetic divergences among Omicron’s sub-lineages, as BA.2 is demonstrating. The evolutionary capacity of a virus is quantified by its effective reproduction number (Rt), which is the total number of secondary infections that a case generates in the population. The first variants evolved in this way; Alpha and then Delta were each about 50% more infectious than the previous one. Today, with a high number of theoretically protected subjects (by vaccination or previous infection) Sars-CoV-2 could optimize its transmissibility (Rt) by further increasing the ability to reinfect immune individuals. Potentially – the authors of the study write – the prospect of a greater severity of the disease in reinfections is not excluded. In practice, any new variants, like Omicron, may not necessarily have a preference for the upper respiratory tract over lung tissue.
“Viruses mutate in all parts of their genome, Sars-CoV-2 has an RNA composed of 30 thousand bases – says Carlo Federico Perno, director of the Microbiology Unit at the Bambino Gesù Children’s Hospital in Rome -. In the beginning, the mutations happen by chance and all the new strains unable to transmit themselves disappear. There are millions of possible combinations, but only some give rise to viruses capable of “functioning”, that is, being transmitted from one man to another and replicating itself more and more efficiently. The pre Omicron variants had little difference from the previous ones, while Omicron had a massive variation. We cannot rule out the arrival of a new variant because Omicron infects tens of millions of people every day. According to a study recently published in Lancet, the population that came into contact with the virus in the world would be three times more than the official number (which takes into account only those subjected to swabs). The more the virus circulates, the more chances it will mutate. And we cannot exclude the formation of an even more “perfect” variant with 50 mutations of Omicron, at the level of transmissibility, replication and immune escape. Your vaccines will likely need to be updated, so don’t give everyone the fourth dose for now. Subsequent boosters will probably be done with different vaccines. With Omicron, the vaccines created protection at the bottom of the trachea, preventing the infection from reaching the lower respiratory tract, lungs and bronchi, as it did before vaccines were available. We hope that this protection will not disappear even with any new variants ».
In an article published on New York Times
, some scientists from the University of Chicago and the Fred Hutchinson Cancer Research Center in Seattle, point out that “there is no reason, at least from a biological point of view, that the virus does not continue to evolve.” According to an expert calculation, about 2 thousand mutations are still possible in the part of the virus that attacks human cells (RBD, receptor-binding domain, found on the Spike protein). And Sars-CoV-2’s response to evolutionary pressure has proven extraordinary, making it better and better at spreading – today it’s much more contagious than other human respiratory viruses. Will the virus further increase its transmissibility? It is possible, even if the process will have to come to an end sooner or later. Other viruses have achieved a plateau in their diffusion capacity and presumably Sars-CoV-2 will behave the same way.
A theme that will have to be evaluated is that of the immune leak which, in the case of Omicron, combined with a very high transmissibility, has created a “perfect storm”. Among the previous variants, some such as Beta and Gamma, had mutations linked to the immune flight, but fortunately they had limited diffusion and did not become dominant. This happened with Omicron. The idea of the experts is that now the virus could continue to “refine its weapons” to infect immune subjects and it is possible that in the future it could cause more serious forms of disease than those we see today with Omicron. “Immune runaway is a never-ending evolutionary race, because the immune system can always develop new antibodies and the virus has a vast array of mutations to explore in response,” the experts write in the New York Times. Omicron has only a small fraction of the many mutations that have been observed in Sars-CoV-2 or related bat viruses, which are themselves only a small fraction of what the virus could explore, according to laboratory experiments. ” .
“We expect that Sars-CoV-2 will continue to cause new epidemics, but will be increasingly driven by the ability to bypass the immune system – the experts conclude -. In this sense, the future could resemble seasonal flu, where new variants cause waves of cases every year. If this happens, vaccines may need to be updated regularly in a similar way to flu vaccines, unless broader variant-proof vaccines are developed. How much this all counts for public health depends on how sick the virus will make us. This is the most difficult prediction, because evolution selects viruses that spread well, and whether this causes disease severity to rise or fall is mostly a matter of luck. But we know that immunity reduces disease severity even when it doesn’t completely stop infections and spread, and the immunity gained from vaccination and previous infections helped to blunt the impact of the Omicron wave. Updated or improved vaccines and other measures that slow transmission remain our best strategies for managing an uncertain future ».
March 29, 2022 (change March 29, 2022 | 15:57)
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