Tuesday, July 27

What will happen to the coronavirus if we let it roam?

The UK is about to start an experiment with just over 50% of its population fully vaccinated. As of July 19, the only official restrictions against COVID-19 will be isolations from infected people. The rest will be left to individual responsibility. More or less peaceful coexistence seems the only strategy against a virus that will not disappear, although some British researchers consider hasty a decision that, according to health secretary Sajid Javid, could cause the number of daily cases to exceed 100,000 throughout the summer.

The COVID-19 vaccines have brought optimism, but also new uncertainties. “Many people ask me what is going to happen [tras la apertura de Reino Unido en pleno aumento de casos]. I have no idea. And you neither”, assured on Twitter the infectologist of the Hospital of Tropical Diseases of London Neil Stone. The rest are models, theories, opinions, hopes and, also, something of catastrophism. All this seasoned with a good dose of social fatigue and concern about a post-pandemic whose effects will go beyond the economic.

Right now all eyes are on the UK case and hospitalization figures, both on the rise, although infections are showing signs of slowing down. The big question is whether he will hold out shed in a country where half the population has not yet been vaccinated, despite the fact that most vulnerable people have received both doses.

The worst of the pandemic is behind us, vaccines will make sure of it. However, uncomfortable saturation situations can still be experienced. One of the largest hospitals in England you had to cancel your cancer surgeries. In Scotland, one of the most important centers has activated the “black code” due to lack of staff due to isolations and vacations. The waiting in the emergency room they reach nine hours in some places.

The director of Health Emergencies of the WHO Michael Ryan assured that allowing more people to become infected is something that, throughout the pandemic, has been demonstrated as a “moral vacuum” and “epidemiological stupidity”. But, apart from contagions and hospital saturations, how will SARS-CoV-2 take this new freedom from an evolutionary point of view?

“Continued high levels of transmission will offer more opportunities for new variants to emerge or for existing ones to acquire new mutations,” Stephen Goldstein, an expert virologist in the evolution of coronavirus from the University of Utah (USA), explains to elDiario.es. “It is not a question of whether this will happen or not, it is something that will happen for sure.”

The Carlos III Health Institute researcher María Iglesias agrees: “The more transmission, the more possibilities there are for changes to appear that generate new variants that may be of concern.” Goldstein, for his part, clarifies that it is inevitable that SARS-CoV-2 will continue to evolve and that new variants will appear over time “no matter what we do.” However, “this process will take place more quickly” if infections increase.

Iglesias says it is important to keep in mind that the vaccinated population is growing. “I don’t know if there will be such an uncontrolled transmission [como se teme]. In Spain, for example, we are already vaccinating those under 30. “He does think that changes may appear if infections continue among people who are not yet immunized.

The researcher at the University of Valencia Rafael Toledo agrees that the chances of a virus mutation increase with its multiplication, but he remembers that the possible changes are limited because SARS-CoV-2 must seek a balance between infecting the virus. cell and escape the antibodies.

In this sense, Iglesias defines the appearance of the delta as “a small milestone” at the spicule level. “You can see how the virus begins to close in order not to be so exposed and that means that the pressure of the antibodies and the protection of the population is being noticed,” he says. This is a substantial change compared to other variants such as the British one, with a much more open spike that “went all-out” to bind to the receptor at the cost of being more exposed to neutralizing antibodies.

“The delta spike is more closed but, even so, it is very efficient in fusion with the cell,” he adds. In other words, “it protects itself from antibodies and, at the same time, is efficient infecting”. Iglesias thinks that this variant opens a new scenario in which “interesting” changes may appear that further modulate the position of the spicule to the point of “closing it more and affecting the transmission and escape of neutralizing antibodies.” Delta will not be the last variant we see, but its current dominance will determine the evolutionary future of SARS-CoV-2.

The number of vaccinated people who become infected will increase by pure statistics, since they will increasingly represent a greater percentage of the population. Even if these people do not have symptoms or these are mild, could SARS-CoV-2 learn to avoid vaccines if it is transmitted in this group?

Goldstein considers “difficult to predict” the effect that the inevitable infections of vaccinated people will have due to the balance between two factors. “When someone fully vaccinated becomes infected, there is, on average, less replication of the virus and, therefore, fewer opportunities for mutations to arise,” he clarifies. However, he also believes that the selective pressure is “stronger” for escape mutations to appear if the virus replicates in the presence of antibodies.

The founder of the biomedical company Nference, Venky Soundararajan, has tried to shed some light on that difficult question. His team this month shared a pre-publication pending peer review in which they looked at how vaccines affected the genomic diversity of SARS-CoV-2.

The results, according to Soundararajan, showed that the diversity of mutations “is greater in sequenced viruses from unvaccinated patients than in vaccinated ones.” That is why he believes that “the most dangerous thing” is that transmission takes place between groups of unimmunized people, and that it is this that “increases the chances” that better adapted variants will emerge.

Soundararajan is confident that vaccines can evolutionarily corner the coronavirus. “If immunization campaigns are truly global and include low- and middle-income countries, this will push the evolution of SARS-CoV-2 into a dead end.” It emphasizes the importance of speed in protecting the planet, including the most vulnerable and neglected populations: “The faster we move towards mass vaccination, the lower the chances that there will be variants that escape the great vaccines we have today. “.

At the moment, Soundararajan’s wishes are far from being fulfilled. While 80% of the available doses have ended up in the arms of people in high-income countries, only 1% of the poorest people on the planet have at least one dose. If the panorama does not change, This could extend the immunization campaign until 2023.

Iglesias doesn’t think booster doses will be needed, but she’s used to vaccine leaks from her work with the flu. “It is something that we study every season in the respiratory virus surveillance networks and it would not be dramatic [que ocurriera] if it does not lead to a severe form of the disease, “he explains.

“Right now it is difficult for the virus to avoid the protection of the vaccine in most of the population,” he reassures. “If it happens, there are surveillance networks in all countries and the pertinent measures would be taken, without alarm and as is already the case with other respiratory viruses for which we have vaccines such as the flu.” In the case of SARS-CoV-2, RNA technology would allow updating in a matter of weeks if “a reminder dose each winter were to be given to the population at risk.”

Cirad researcher Serafín Gutiérrez affirms that the probability of emergence of new variants is a complex process based on many factors. These include the number of infected and the mutational capacity of the virus. “SARS-CoV-2 has already shown that its mutation rate is high enough to produce new variants when many people are infected. Much of the world’s population remains unimmunized, so it is easy to imagine what could happen. happen if there are many infections again, “he explains.

Gutiérrez adds that there is another important factor to consider: the competition between the variants themselves by the hosts. “There are fewer and fewer people with an immunity that allows infections, so new variants will have little chance of being transmitted on a large scale if existing ones are already better transmitted.” It is something that has been seen often throughout the pandemic and that has caused variants like epsilon are today on the brink of extinction.

What variants can emerge in the midst of this fierce struggle? Those that are transmitted better than the previous ones and that are capable of infecting people immunized against those that already exist. “There is a scenario that maximizes the probability of emergency: a population with immune and non-immune people in similar proportions, half and half,” explains Gutiérrez. In this scenario, “if the virus circulates on a large scale among the non-immunized, many variants will be generated. Some of the new variants may be capable of infecting vaccinated or previously infected people.”

With 50% of people not vaccinated, the United Kingdom is the ideal example set by Gutiérrez. For this reason, the researcher concludes that “as long as a high group immunity is not reached, it is not necessary to allow the high circulation of the virus”. As he warned in a previous article: “Evolution is largely a game of chance. Hopefully certain cards won’t come out.”

In biology the hypothesis of the Red Queen is well known, which takes its name from the character of Alice through the mirror that he kept running to stay where he was. In a similar way, species must continually adapt just to maintain status quo. The immune system does something similar when faced with a parasite, and in this arms race it is not only SARS-CoV-2: our body has a lot to say.

Toledo says that it is important to understand that our immune system is dynamic: “It first interacts with the virus and then evolves with it to adapt to its modifications.” The interaction between parasite and host is not all or nothing, 0 or 100. That is why we can live with the flu, colds and respiratory syncytial virus.

“The immune system gradually adapts and modulates the pathogenesis.” The problem, he says, is when our body faces a new pathogen. This is what happened with SARS-CoV-2, but also with the flu in the indigenous communities of America or with the bronchiolitis of the little ones. “They say that the flu is not fatal when compared to COVID-19, but of course it is if the immune system is not prepared,” adds Toledo. The best example was the 1918 pandemic: “It continues to exist like one more flu because it was self-modulating when a significant number of people passed it.”

“The pandemic will end and natural infections and vaccines will accelerate its end and even reduce infections,” concludes Toledo. “If we did not have so much diagnostic pressure and we analyzed according to clinical data instead of looking asymptomatic, the profile that we would have of the pandemic would already be different.” As the coronavirus moves into its next phase, the world holds its breath awaiting the outcome of the British bet.


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