Experts: the possibility of new crown mutations will always exist, but the emergence of more "bad" variant strains of pandemic probability is small

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Recently, some scholars have suggested that Omicron is more infectious, but its virulence has declined, and the mutation has basically saturated, so the possibility of mutating a more virulent strain is unlikely. Is it true that the new coronavirus is at the “end of its rope” and has become evolutionarily stable? Virologists in China recently said in an interview that the possibility of new variants of the new coronavirus will always exist, but it is difficult to have a pandemic of more “bad” variants, we should look at this issue rationally and continue to strengthen the surveillance of mutant strains in the future.

The possibility of new variants will always exist

“BA.5.2 and BF.7 are the absolute majority of the national epidemic, and together, they have reached more than 80%, with seven other subtypes.” Xu Wenbo, director of the CDC’s Institute of Viral Diseases, said in a recent media interview that nine subtypes of Omicron have been detected as being prevalent nationwide, and no characteristic genomic mutations have been found for these subtypes. Meanwhile, from December 1 to now, a total of 31 subbranches of Omicron have been found to be imported into the country, with BA.5.2 and BF.7 still dominating.

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In the face of the widespread prevalence of the evolutionary branches of Omicron mutant strains in China, some scholars recently said in a media interview that the mutations of Omicron mutant strains “have basically saturated” and the possibility of causing new variants is not too great.

In response to this view, Lan Ke, director of the State Key Laboratory of Virology at Wuhan University, said in an interview on Dec. 29 that the new coronavirus, as an RNA virus, has the characteristic that RNA replication is prone to random mutations, which determines that the genes of such viruses are subject to random mutations during the process of reproduction in the host. With the widespread spread of Omicron mutant strains and their evolutionary branches replicating in the population, the number of viral mutations will also increase and the possibility of new variants will always exist,” said the new coronavirus S protein, which also has the potential to generate new mutant combinations. Therefore, it is still necessary to strengthen the monitoring of mutant strains,” Lan Ke said.

On December 27, the National Health Commission released the “New Coronavirus Infection “Category B B tube” epidemic surveillance program, which clearly pointed out the need to strengthen the monitoring of virus mutations, around the land, air and seaport port city arrivals, sentinel hospital patients, key sites and key populations in the nucleic acid test positive specimens. The whole genome sequencing of the new coronavirus was carried out for specimens of severe and fatal cases, and the sequences were sent to the Institute of Viral Diseases of the Chinese CDC on time. We will keep track of the mutation trend of virus strains in real time, capture new mutations in time, and analyze the impact of mutations on virus characteristics and immune escape ability.

Liang Wannian, head of the expert group of the National Health Commission’s Leading Group for New Crown Epidemic Response, also pointed out in a media interview on the 29th that China is very concerned about monitoring the mutation of pathogens and is also actively involved in global pathogen surveillance. Once new variants are found, or mutations that lead to changes in virulence, transmission, virulence and other aspects of the virus, China will promptly notify the World Health Organization, and more importantly, we will make the system alert and do a good job of optimizing and adjusting the prevention and control program, medical treatment and other aspects.

More likely that the new strain will evolve in the direction of “strong transmission and weak pathogenicity”

Looking back over the past three years, it is easy to see that the mutations of concern that are prevalent or have been prevalent around the world usually did not evolve from the previous dominant mutant, but rather from different strains. For example, the more virulent Delta strain was first discovered in India and quickly swept the globe causing a pandemic, but as the more virulent and less virulent Omicron strain emerged in South Africa it quickly took over from Delta, yet Omicron did not evolve from the Delta strain. The question of the evolutionary direction and pattern of the new coronavirus is also the focus of academic discussion.

Zhong Nanshan, an academician of the Chinese Academy of Engineering, previously said in a media interview that he had talked with pathogenic experts who believe that the future evolutionary trend of the new coronavirus, the virulence is likely to weaken, “No one said it will definitely weaken, but we have to follow the most universal laws to think about the problem and make decisions.”

Xu Wenbo also recently said at a State Council press conference on joint prevention and control mechanisms that the cases of hospitalization, death, and severe illness caused by Omicron are significantly lower than those of the earlier Delta strain and other VOC mutations. no significant increases in severe illness and death have been observed in more than 700 branches, and overall, mutations into strains with significantly increased pathogenicity are less likely. In addition, the population is now somewhat immunized by vaccine or natural infection, which provides better protection. Unless some subversive recombination of the virus occurs, resulting in complete immune escape, it would increase the risk of transmission, but this is relatively unlikely. So, overall, it is relatively unlikely that the virus will mutate to a strain that is both highly infectious and highly pathogenic.

Chen Yu, deputy director of the Department of Life Sciences at Wuhan University, expressed similar views in an interview with reporters on the 29th. Chen Yu said that if there is no selection pressure, the mutation of RNA viruses, including the new coronavirus, during reproduction and replication should be random, so its mutation itself is not directional. However, viral evolution is the result of the interaction between viruses and their living environment. After the elimination of superiority and natural selection, the mutant strains of viruses that are more favorable for survival will be given the opportunity to spread and reproduce, while the maladapted strains will be gradually eliminated, which will lead to the directional evolution of viruses.

Chen Yu further pointed out that in the process of the new coronavirus transmission mutation, due to the production of antibodies in the body of the recovered, coupled with the use of vaccines, drugs, and people to avoid contact with fever patients and other human behavior, it is bound to provide selection pressure on the evolution of the virus, eliminating the unadapted virus mutant strains, which makes the virus evolve mainly in two directions: one tends to be more transmissible, while the low pathogenicity of the virus mutant strains will gain a transmission advantage; the other is that the virus will also evolve in the direction of being able to escape host immunity, i.e., it will only gain access to infection and replication if it has escaped the action of neutralizing antibodies in recovered and vaccinated individuals. This is the reason why Omicron has shown a substantial increase in transmission ability and immune escape ability compared to the previously prevalent strains, while the pathogenicity is significantly weakened.

Chen Yu believes that the probability is that Omicron will still evolve in this direction in the future. “In this process, even if a more pathogenic strain emerges, it is difficult to have a transmission advantage and less likely to become the dominant strain in the epidemic, so it is difficult to have a pandemic situation with a more ‘bad’ variant. This is an inevitable pattern for such RNA viruses to become epidemic in human society.”

Developing broad-spectrum vaccines and drugs to eventually eliminate the effects of virus evolution

The view that “new coronaviruses are difficult to eradicate in a short period of time, but exist in humans for a long time” has basically become the consensus of the academic community. How can we further eliminate the adverse effects of the evolution of new coronaviruses in the future and effectively reduce the harm caused by mutant strains of new coronaviruses? According to Lanke, it is more likely that neo-coronaviruses will evolve toward lower pathogenicity and become another relatively mild “seasonal” common respiratory disease with symptoms similar to the flu, and less likely to evolve into a more threatening virus. Close ongoing monitoring of the neo-coronavirus genome will allow us to assess changes in transmission and pathogenicity in the first place.

As newer iterations of the neo-coronavirus vaccine and vaccination coverage increase and antiviral drugs continue to be developed and introduced, they are also thought to provide a stronger umbrella of protection for human health security. “It is difficult for us to predict the future, or even the epidemic situation next year, and it is not known whether there will be a peak in the epidemic. It is entirely possible for individuals to have some recurrent infections. But I believe that the future of the prevention and control of the new crown epidemic remains in human hands, partly because vaccines are being updated and iterated and vaccination coverage continues to improve, and partly because new drugs are continuing to be developed and introduced. People are also becoming more experienced in prevention and control, and there is the added benefit of an immune barrier. A fourth dose of vaccine has been issued for implementation in China, and regular immunization is likely to be normalized in the future, depending on the rate of mutation of the new coronavirus.” Lan Ke said.

At the same time, Lan Ke believes that a more ideal state would be to be able to start with basic research and find breakthroughs to develop broad-spectrum vaccines and drugs, which is the only way to help humans get rid of the virus evolution completely.