Where is the evolution of the new crown behind Omi Keron?
In Sun Yamin's laptop, there are data maps of COVID-19 variants in different periods.
Most of the curves are in the shape of an inverted U. As time goes by, they climb and climb to the top, then descend and almost disappear. Each line corresponds to the minimal history of the appearance and retreat of the new crown mutant in human society.
The speed of "iteration" of the new crown is faster than that of electronic products.
Soon after Alpha became a mainstream popular strain, Delta came aggressively; Delta also had the breath of "rookie", and Omi Keron had become the focus within a few days.
It changes so much and "upgrades" so quickly that none of its predecessors can compare it.
But Omi Keron is nothing special.
In the past two years, the variation of the new crown has been like the trees that continue to shed their branches and leaves. From time to time, new members of the family have grown, and older members have also undergone micro-apoptosis.
Omi Keron is not the first, and it is highly probable that it will not be the last.
The "unusual" Omi Keron
On the evening of November 26, the computer in the studio of Professor Sun Yamin of the Institute of Public Health and Health of Nankai University began to work overtime throughout the night, reading more than 5 million genome data one by one.
ATTAAAGGTTTATACC...These independent documents in fasta format are filled with letters symbolizing four bases, each of which is the life code of a new coronavirus that has briefly appeared in the human world.
Some are exactly the same, some are not the same. They come from human laboratories around the world, and from the beginning of the epidemic to the present, they have gathered into a huge pool of new coronavirus data.
The tentacles were sunk into this "pool" again in order to explore the 131 variants.
Since then, the World Health Organization named it Omicron (Omicron)-the most important type of new crown variant currently classified.
Prior to this, only four of the many mutant strains that have evolved from the new crown were included in VOC.
Alpha, Beta, Gamma, Delta.
From the upload of the first sample to the WHO naming and rating, this process generally takes several months, and is often accompanied by an obvious epidemic in the human world.
Omi Keron is an exception. It takes about half a month from data upload to naming, from being listed in VUM (Variants Under Monitoring by WHO) to skipping VOI (Variants of Interest). Variant strain) "Helicopter" VOC, only took 2 days.
However, for Sun Yamin, the new crown mutation is nothing new.
After two years of epidemics in the world, the number of mutations of the new coronavirus is only a negligible proportion of the total number of nearly 30,000 nucleotides.
The next day, the computer ran through all the genome data, and Sun Yamin was truly surprised when he saw the report.
In the horizontal comparison of more than 5 million pieces of historical data, Omi Keron is indeed unusual: there are many mutation sites, and the location is critical.
According to calculations, the new coronavirus has only gradually accumulated about 35 heritable non-synonymous mutations (which can lead to amino acid changes, and it is generally believed that non-synonymous mutations are affected by natural selection). On this basis, Omi Keron, There were about 15 more mutations in one breath; more than 30 locations are located on the spike protein on the surface of the most concerned new crown, half of which are located in the RBD region, which can directly affect the replication and spread of the virus; more than 10 are located in the ORF1ab region, possibly Affect human immunity.
Omi Keron also appeared to be a mystery.
When the virus reproduces from parent to offspring, it will leave traces on the genetic level. Scientists can trace the "family tree" of virus mutation based on these traces.
Omi Keron was first discovered in South Africa. In the last three months, most of the mutant strains isolated from South Africa were Delta. Sun Yamin originally thought that Omi Keron should have been mutated from Delta, but the data showed that Omi Keron Rong and Delta are not closely related.
Even in the entire data pool, Omi Keron's sudden new mutations cannot find a gradual evolutionary history.
What are we talking about when we discuss mutation?
When Sun Yamin tried to describe the entire history of the mutation of the new crown, it was a process of continual bifurcation, a bit like the growth of a tree-gradually branching out more and more branches from a main trunk.
But it's not entirely: While some branches and leaves are rapidly luxuriant, the other part grows slowly or quickly withers.
"In the initial virus, if there are hundreds of variants, some of the advantageous variants will evolve into hundreds of variants after spreading for a period of time. In each period of the virus epidemic, there will be dominant groups appearing, but Not all variants will survive, most of them will be eliminated, and the once dominant strains may also be replaced by rising stars.” Sun Yamin said.
As Sun Yamin said, the "evolutionary tree" of the new crown has grown in this wonderful way for nearly two years.
The first key mutation D614G in the new crown was at the end of January and early February 2020.
This mutation site in the spike protein makes it easier for the virus to attach to human cells and enhances the infectivity of the variant.
Later, from Europe to North America, Oceania, South America... After 4 months of transmission, this variant replaced the previous new coronavirus and became the main epidemic and strong variant.
By September 2020, a new variant of the new crown appeared in the UK. Two months later, scientists began to isolate this variant repeatedly from newly infected people.
On December 18, the WHO named it Alpha.
After that, Beta, Gamma, Delta and Omicron appeared one after another.
Of course, we can use a single strain to tell the story of the mutation of the new coronavirus.
These small particles that have set off storms in the human world always appear unclear, strange and menacing, making people nervous.
But in nature, virus mutation is like human breathing and eating, which is an extremely common natural phenomenon.
"You can imagine that you have to copy 30,000 different letters by hand at the fastest speed. At this time, you will find that there will be many errors in the process of copying. Constantly rewriting, you will continue to make mistakes. , This is the principle of the mutation of the new coronavirus." said David Matthews, a professor of virology at the University of Bristol in the United Kingdom.
As the largest and most complex RNA virus, the coronavirus can have a genome consisting of up to 32,000 nucleotides, and the new crown has nearly 30,000 nucleotides.
In the WHO's assessment and classification of the new crown, the assessment object is defined as a "variant strain" (Variant). In fact, as long as one nucleotide is mutated, a new variant strain (Variant) will be formed.
Jiang Rongmeng, an infectious disease expert at Beijing Ditan Hospital, explained that the new coronavirus is an extremely simple organism. The outer protein contains the internal genetic material and relies on host cells for replication and reproduction.
Compared with DNA viruses, which have a complex, compact and stable double helix structure, the genome of the new crown is a single-stranded RNA, which is very simple and is more prone to errors during the replication process.
In addition to the spontaneous mutation caused by innate characteristics, the pressure brought by the external environment, such as temperature and climate changes, host immunity, drug attack, etc., will also make the virus have to mutate to adapt to the environment.
Viral mutations are always in the progressive tense. Even in the same patient, virus samples isolated at different time periods may have different genomes.
This is true for the new crown, and so are other viruses, and there will even be a more mature and huge "family tree."
Jiang Rongmeng used influenza virus as an example: According to the difference of nucleoprotein, influenza virus can be divided into four genotypes (genotypes) of A, B, C, D, among which the influenza A and influenza B are more common in human society, and researches are also focused on this; genes; Under the type, influenza A can be divided into different subtypes according to the difference between the two proteins of hemagglutinin HA and neuraminidase NA on the surface of the virus. This is the frequently mentioned H1N1, H3N2, etc. The origin of the law: Yiliu does not make subtype classification, but can be divided into different lineages, such as Yamagata, Victoria and so on.
The rate of flu mutation is much faster than that of COVID-19, and the variant strains that are circulating every year are also different. Every autumn and winter, the disease control department calls on citizens to receive flu vaccines, and the ingredients must also be adjusted according to the latest predictions of experts.
If compared with the flu, the degree of mutation of the new crown seems to be far less than the former.
"If it is classified according to the conventional genotype, even Omi Keron, which has more than 30 mutation sites (on the spike protein), is still of the same genotype, or subtype, as the existing mutant, and has not differentiated into Independent genotype." said Lu Mengji, a professor at the Institute of Virology at the University of Duisburg-Essen, Germany.
Matthews also said that although Omi Keron still needs to be understood, he does not believe that the new crown virus has undergone major mutations at this stage.
Even at the genome level, viruses can mutate to a greater degree, and mutation is still a "metaphysics."
According to Sun Yamin, most of the mutations are meaningless.
Although the gene has changed, it does not necessarily affect amino acids and cannot bring about higher-level changes in virus structure. Structural changes are the basis for changes in virus "ability". This is why the mutation of the new crown spike protein RBD region is the most important reason. -Its shape can directly affect the fit between the "key" of the virus and the "keyhole" of the human receptor.
The remaining part of the meaningful mutations diverged in two directions. Some allowed the virus to gain more survival advantages, and some made it easier for the virus to "die early."
The authoritative medical journal "The Lancet" once published an article from a Singapore research team, which introduced a type of Covid-19 mutant that lacked 382 nucleotides in the early stage of the epidemic, and this mutant quickly disappeared.
When we discuss virus mutation, we are actually asking the latter: mutation has occurred, and then, how much harm will humans suffer?
Unfortunately, even if scientists can read the core genetic code of the mutant strain in the laboratory, crack the shape and structure of the virus, analyze the influence of the mutation site, and carry out a series of scientific experiments... the laboratory is still too different from the real society. Far, the results obtained in the laboratory may not necessarily occur in the real world.
Perhaps because of this, even if Omi Keron has been seen by us from the genetic level, many experts still said when discussing it that it is not yet understood enough and needs further monitoring and observation.
If the micro results are difficult to predict, then from the macro perspective, will the evolution of the new crown go in the established direction?
Will the evolution of the new crown come to an established end?
"The mutation of the virus is random, and the general evolutionary direction is to increase the transmission power, so we will continue to see the emergence of new variants with stronger transmission power." Lu Mengji said.
From the D614G mutation to Alpha and Delta, the new mutant strains indeed show faster transmission.
The Washington Post pointed out that the delta variant is 55% to 60% more infectious than the alpha variant, almost twice the original new coronavirus.
While the spread is accelerating, whether the virulence will be higher or lower is a more complicated question.
"The virus mutates not to make humans sick, but to survive for its own success. But there are also many possibilities." Matthews said, the virus may spread by making humans sick or even die, or it may become more virulent. It becomes more and more minor, so that the host cannot be aware of the occurrence of the infection, so as to achieve population transmission.
So, judging from the existing mutant strains, is the condition of the infected person getting milder?
"There is still no systematic clinical study that puts patients with different (variant strain infections) together and compares them in reasonable groups. There are too few data and too many uncertainties, it is difficult to say." Lu Mengji said.
Davey Smith, director of the Department of Infectious Diseases and Global Public Health at the University of California, San Diego School of Medicine, mentioned that although the virus is more likely to survive without harming the host, similar changes are also present in other viruses. It did happen, but it usually takes hundreds of thousands of years.
"Although there are reports in South Africa that patients infected with Omi Keron have milder symptoms, it may be due to a problem with the testing method. For the new crown virus that has only been circulating for two years, I doubt that Omi Keron or other variants are really true. Let the symptoms become lighter." Smith said.
Of course, the severity of symptoms does not entirely depend on virus mutations, but also on human pre-existing immunity and individual characteristics.
Matthews said that from an optimistic perspective, the current symptoms of children and young people after being infected with the new crown are not serious. After recovery, they have acquired the corresponding immunity, even if the new crown is still mutating, under the protection of the immune system, the symptoms that appear in humans It will also become minor, and the pressure on the medical system will become less and less.
Smith's prediction is more cautious.
"When people get old, other health problems, such as cancer and rheumatoid arthritis, etc., will weaken the body's immune system. If they are exposed to the virus, the immune system may not be able to compete with it." In addition to being a scientist, Smith is also an infectious disease doctor. He hopes that there will be no more morbidity and death caused by the new crown in the future, "but it is more likely to say that I will directly diagnose new crown patients in my career... and with the mutation If it happens, the new virus may further evade the immune response and even reduce the effectiveness of existing treatments."
In an interview, many experts said that the mutation will continue, and it will be difficult for the new crown to completely disappear from human society.
"The mutation of the new crown will continue. Now it is Omi Keron and there will be other variants in the future." Matthews said. One possibility is that the new crown will leave behind several major variants, which will lead the epidemic in turns around the world. .
For example, Delta is popular in Northern Europe this year, Omi Keron is popular in the following year, and it will be changed back to Delta two or three years later. In different countries and regions, different variants are popular.
Over time, these variants will continue to change.
Sun Yamin said that as the spread expands, the virus may mutate faster and faster.
"The frequency of new mutant strains is not set." Sun Yamin said, the faster the virus spreads, the more people it infects, and the greater the possibility of the virus mutating. When the new mutant strain has a stronger transmission power, the infection Given to more people, it will accelerate the birth of new mutant strains.
When human society does not take necessary restrictive measures, this acceleration process will continue to accelerate.
In addition, Omi Keron's mutation may also suggest another hidden danger.
Many experts have analyzed that the abrupt mutation carried by Omi Keron may not only occur in people with immunodeficiency, but also in natural hosts.
When analyzing the mutation sites of Omi Keron one by one, Sun Yamin's team found that two of the mutations may increase the broad spectrum of the virus host. In other words, this mutation can infect more animals with the new crown.
"The original natural host is not easy to transmit the virus to humans. The new natural host gets the new crown from humans, and they are likely to be very close to human society, such as mice. If the new natural host can be used in the new natural host If it spreads widely, it can exist for a long time in nature and continue to mutate; and this host group that is very close to humans can continue to bring new COVID-19 mutant strains back to human society. This is a relatively bad situation.” Sun Yamin said, However, these are only speculations and need further research and demonstration.
In any case, although humans cannot predict and stop virus mutation, they are not helpless.
Smith pointed out that vaccination is an effective way.
When more people become immune to the virus, the chances of new variants appearing can be reduced.
Lu Mengji said that while actively vaccinating, it is possible to discuss whether it is necessary to produce a new vaccine against the mutant strain.
In addition, traditional simple methods such as wearing masks and maintaining social distance can also provide effective protection.
Jiang Rongmeng mentioned that scientific monitoring is necessary in the face of the continuous mutation of the virus, but there is no need to panic.
"In terms of transmission power, we often use R0 to describe the transmission power of a virus. In fact, R0 is not absolute and will be affected by many factors. Even if the transmission power of a mutant strain increases in a natural state, under effective prevention and control methods, We can still achieve dynamic zeroing."
Beijing News reporter Dai Xuan Luan Ruoxi