Possible options for the evolution of coronavirus studied: prospects are bleak

Recently, experts are increasingly talking about the imminent end of the pandemic. WHO representatives even express confidence that this will happen right in the coming year, and the well-known Russian sanitary doctor Gennady Onishchenko recently said that it was all over.

However, the international scientific team is unlikely to agree with these statements, having published an article in the authoritative journal Nature, which contains a complete analysis of what has already happened and various scenarios for the development of the future, which can hardly be called optimistic.

Scientists believe that SARS-CoV-2 will not get rid of us so easily. So what’s in store for us? What will be the further evolution of the virus that turned the planet upside down?

It is hard to forget that the SARS-CoV-2 coronavirus, which appeared in 2019, caused millions of deaths and a surge in infections worldwide. And today it has acquired the status of perhaps the most studied virus: during the pandemic, an unprecedented amount of genomic data on this pathogen was obtained, which made it possible not only to look for ways to combat it, but also to understand its biology. Each new genovariant of the “crown” has been studied and continues to be studied under a microscope; the names of the strains are familiar to almost every schoolchild in the world. At the same time, if initially almost everyone was sure that with the accumulation of mutations the virus would become, though more infectious, but still less vicious, in fact we do not observe this. New lines of SARS-CoV-2 throw us more and more surprises, rapidly learning to bypass any kind of immunity, it is easier to penetrate the cells of the body – and still cause serious damage in it.

“Tracking the evolution of this pathogen in real time offers hope for understanding the processes that give rise to this diversity, potentially predicting possible future evolutionary trajectories of the virus, and also opens up opportunities for prevention and treatment. To facilitate the realization of these possibilities, it is necessary to critically analyze the main factors of the evolution of SARS-CoV-2 and explain the processes that give rise to the diversity and novelty of the virus, ”the authors of the new work write in Nature.

In their review, the scientists examined the mechanisms that generate genetic variation in SARS-CoV-2. We tried to understand why the virus evolved towards higher transmissibility and, in some cases, higher severity. Scientists have studied how new lines arise, why problematic variants of the virus (VOC) appear that can cause chronic infection, what role our smaller brothers play in the evolution of SARS-CoV-2.

And after analyzing the data, they developed scenarios for possible future evolutionary trajectories of SARS-CoV-2.

From Alpha to Omicron

Recall how the virus that fell on our heads at the end of 2019 evolved. First there was the Wuhan strain, which no one really called it that. But at the end of December 2020, a new lineage of SARS-CoV-2 was identified, which WHO designated as of concern (VOC) – “Alpha”.

And then it started. In the weeks that followed, South Africa and Brazil reported two additional rapidly growing lines, Beta and Gamma. The Delta line, recognized by the VOC in May 2021, quickly supplanted the previous ones and led to a sharp surge in cases around the world.

In November 2021, Omicron initiated new global waves of infection. Although all of these VOCs originated in different parts of the world, they shared common sets of mutations. And each new variant had a growth advantage over its predecessor variants.

…Mechanisms of the evolutionary origin of VOC are still the subject of debate. Several hypotheses have been put forward to explain their occurrence: persistent occult circulation of SARS-CoV-2 among humans in areas with weak genomic surveillance; zoonotic circulation of SARS-CoV-2 in animal reservoirs; chronic SARS-CoV-2 infections in immunocompromised people.

In the first hypothesis, genomic surveillance has been highly uneven around the world, with less than 0.5% of sequencing in many low- and middle-income countries. This extreme undersampling results in some viral lineages circulating undetected, allowing for long-term latent viral evolution.

If we talk about the possible circulation and mutation of viruses in the body of animals, then today only three possible applicants are known that effectively transmit SARS-CoV-2: Syrian hamsters, minks and white-tailed deer. But. No specific viral genetic adaptations have been found in the Syrian hamster. Mutations in SARS-CoV-2 found in mink and white-tailed deer are host specific. And although the SARS-CoV-2 genetic sequences in mink in the Netherlands and white-tailed deer in Canada suggest accelerated evolution and potential for transmission from animals to humans, the combination of mutations in these viruses is very different from those found in viruses in humans, which suggests a different path of evolution. “At present, there are no convincing arguments confirming the origin of dangerous variants of coronavirus in animal reservoirs,” the scientists conclude, but still suggest keeping these reservoirs on a pencil.

And finally, the third hypothesis: mutations as a result of long-term carriage of SARS-CoV-2 in people with weakened immune systems (cancer patients undergoing immunosuppressive therapy, HIV-infected, etc.). In such people, due to an inferior immune system, the virus can remain in the body for a long time, which leads to its long-term persistence (that is, constant reproduction). It has been hypothesized that in the course of such persistence, the virus can mutate, thus creating new lines. It is also believed that the selection of new virus genovariants in chronically infected people occurs under the influence of treatment (plasma, monoclonal antibodies). Facts of direct transmission of mutations from patients who are chronically infected have been recorded. “Locations with high levels of monoclonal antibody use may have created an environment that breeds viral diversity that can be rapidly transmitted between people,” the review says.

… And yet there is no complete clarity on this issue. There is no understanding of a clear pattern of SARS-CoV-2 evolution in all chronic infections, nor of how common the emergence of variants that enhance transmission of the virus in these infections is. It is also unclear which forms of immunosuppression are associated with chronic infection, and their prevalence in the population has not been determined. But researchers believe that some lines of SARS-CoV-2 arose in this way.

His future is either empty or dark

Until the end of 2021, scientists hoped that the coronavirus would give those who had been ill and immunized strong immunity. However, the subsequent emergence of new options that bypass any kind of protection forced to dismiss this scenario. So, “Omicron” was able to force out “Delta”, because it easily bypassed the immunity that it gave to those who had been ill; and the different sub-variants of Omicron that have appeared have learned to overcome each other’s immunity.

Therefore, it is now easy for scientists to imagine future scenarios in which two or more lines of the virus circulate together, or where one of them leads the others to extinction. “Such an interaction could have profound consequences for public health, because it does not rule out new large-scale waves of infection,” the scientists said.

The authors of the work predict that with further circulation of variants of the Omicron family, immunity caused by a combination of vaccination and previous infection will protect against severe disease upon reinfection. At the same time, they predict outbreaks of new waves of infection every 4 months of the circulation of the virus. And assuming that the mortality rate from SARS-CoV-2 in people with prior immunity is similar to that from seasonal influenza, the annual influenza burden can be expected to be two to three times greater. With the proviso that this forecast does not take into account patients with post-COVID.

Corona is expected to become a seasonal virus someday. Although recently biologists are increasingly doubting this. In addition, the summer outbreaks of 2022, caused by lines originating from Omicron, indicate that a regular seasonal pattern may not come soon.

But there is an alternative to the optimistic scenarios described: a new variant will appear with a completely different set of mutations and properties, which will allow the virus to bypass the immunity created by the previous infection or vaccines. This may occur as a result of the accelerated evolution of the virus during long-term persistence in immunocompromised individuals. At the same time, it is difficult to predict the virulence of new strains: it is quite possible that variants will appear that cause severe illness in more people than Omicron.

Unexpected but significant changes in the genetic structure of the virus and in its properties are also not excluded. Most of all, in this regard, researchers are afraid of recombinations – when different strains with unpleasant properties give rise to one that “inherits” all these properties. Such examples are already known.

Unlikely, but, alas, very sad scenarios are also possible: that SARS-CoV-2 will take and cross with another virus altogether. Then, the authors of the work believe, the situation will change radically, which in translation means that we are all covered. The virus can change the form of transmission, the course of the disease, or learn to completely destroy protection against serious illness and death.

Since the complete eradication of SARS-CoV-2 no longer shines for us, it should become endemic (constantly present), but the process of its transformation into a “quiet neighbor” may take decades. “Endemic SARS-CoV-2 is by no means synonymous with safe infections, mild COVID-19, or a low burden of mortality and morbidity in the population,” the authors warn. And they recognize that the future evolutionary trajectory of the virus will always remain unknown in many crucial details.

Expert of the National Medical Association for the development of expert activities in the field of laboratory diagnostics “MedLabExpert” Alexander Solovyov comments that we should prepare for a long and inconsistent transition from a pandemic to a future endemic state: “We need to be prepared for a negative scenario – the emergence of a new version of the virus with a completely different “constellation of mutations” and with altered clinical manifestations of infection. The unpredictability of virulence evolution could mean that new variants of the virus will cause severe forms of the disease in a large number of people.”

Scientists have yet to figure out how to calculate the appearance of new VOCs, or at least understand when to prepare for their arrival. They hope that they will learn to predict possible mutations ahead of time in order to be warned and have time to arm themselves. And the first steps towards this have been taken.