The new coronavirus mutates quickly and spreads easily across species. We need to be alert to the return of mutant strains popular in animals to humans.

Since the outbreak of the new crown epidemic, due to different prevention and control efforts, the new crown epidemic in some countries has repeatedly been repeated, and even out of control for a certain period of time
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This situation has made it more difficult for the world to effectively fight the epidemic, and China is facing the threat of imported viruses from abroad

Since the outbreak of the new crown epidemic, due to different prevention and control efforts, the new crown epidemic in some countries has repeatedly been repeated, and even out of control for a certain period of time

This paper summarizes the classification, temporal and spatial distribution and epidemic dynamics of the main mutant strains of the new coronavirus, as well as the key mutation sites and their impact on the biological characteristics of the virus.

With the continuous mutation of the new coronavirus, the protective efficacy of existing vaccines against the infection and lethality of the new coronavirus variant has declined, especially the emergence and prevalence of the new coronavirus variant strains Delta and Omicron, which has caused the new crown epidemic to rebound in many countries, even in Countries with high vaccination rates

Research on the genetic evolutionary origin of the new coronavirus can help formulate corresponding strategies to cut off the transmission route of the virus from its natural host to humans at the source

At the same time, strengthening the monitoring of the cross-species transmission of the new coronavirus is of great significance for preventing and controlling the epidemic of the new coronavirus in animal groups in nature, as well as preventing and controlling the mutation of the virus in animals that is more suitable for humans

Variation dynamics of 2019-nCoV and its correlation with transmission and virulence

mutant strain

mutant strain

Coronaviruses are the RNA viruses with the largest known genomes
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The new coronavirus is a single-stranded positive-stranded RNA virus with a genome size of about 30,000 bases.

Since the end of 2020, the WHO has used Greek letters to group the new coronavirus variants that are widely prevalent in the world and have greater public health risks.
According to the public health risk of the virus, the new coronavirus variant strains are divided into three groups in turn: "mutants worthy of attention" (VOC), including Alpha, Beta, Delta, Gamma, and Omicron mutants; "mutant under observation" (VOI), including mutant Lambda and Mu; "variant under surveillance" (VUM)
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The mutant strains in each group are dynamically adjusted according to the epidemic transmission, biological characteristics and public health significance of the mutant strains
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Among them, VOC variants need the most attention, which are characterized by: increased transmissibility or aggravated epidemiological characteristics; increased pathogenicity or changed clinical manifestations; reduced the effect of public health prevention and control or affected diagnosis, vaccines and treatment methods
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Increased transmissibility or aggravation of epidemiological features; increased pathogenicity or altered clinical manifestations; decreased effectiveness of public health prevention and control or affected diagnostics, vaccines, and treatments,
etc.

Temporal and spatial distribution of mutant strains and public health risks of key mutant strains Delta and Omicron

The spatiotemporal distribution of variant strains and the public health risks of key variant strains Delta and Omicron The spatiotemporal distribution of variant strains and the public health risks of key variant strains Delta and Omicron

As of December 23, 2021, the new crown Delta variant strain is the most prevalent strain in the world, with a global prevalence of 59% (the prevalence rate of the variant strain has been ratio to the total number of sequences of all strains)
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New coronavirus variant strains and their key sites and changing trends

New coronavirus mutant strains and their key sites and trends New coronavirus mutant strains and their key sites and changing trends

(a) Time and country when the main SARS-CoV-2 variant was first reported
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(b) The key mutation sites of the S protein of the main SARS-CoV-2 variants

(a) Time and country when the main SARS-CoV-2 variant was first reported

And the binding ability of the Delta mutant strain to the angiotensin-converting enzyme 2 (ACE2) receptor of human cells is also enhanced, which increases the infectivity of the virus
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In addition, clinical evidence shows that the nucleic acid conversion of patients infected with Delta variant strains takes longer than that of patients infected with common virus strains, and the risk of becoming critically ill in patients infected with Delta variant strains is increased by 2.
98 times
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In addition, on November 9, 2021, South Africa identified the new coronavirus variant Omicron for the first time.
This variant strain has 26-32 amino acid mutations in the spike protein (S protein)
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Preliminary studies have shown that the Omicron variant spreads faster than the Delta variant, but causes milder clinical symptoms than the Delta variant, causing more mild to moderate clinical symptoms
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The Omicron variant spreads faster than the Delta variant, but causes milder clinical symptoms than the Delta variant, which mostly causes mild to moderate clinical symptoms
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At the same time, Omicron virus mutation changes the antigenic properties of the virus, reducing the protective efficacy of existing vaccines against virus infection and transmission
.

At present, the Omicron variant has become the predominant epidemic strain in the world

Variation sites are associated with virus transmission and pathogenicity

Correlation of variant loci with virus transmission and pathogenicity

Variations at key functional sites of 2019-nCoV may alter the biological properties of the virus, which can affect the efficacy of vaccine protection and drug therapy, the effectiveness of diagnostic methods, and public health interventions
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Among them, some of the mutations increase the adaptability of the new coronavirus to non-human mammals, and these animals may become the ecological hosts of the potential long-term epidemic of the new coronavirus
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In the global monitoring of the new coronavirus epidemic, it is necessary to pay attention to the mutations related to the biological function of the virus, adjust and update prevention and control strategies in a timely manner, pay close attention to the cross-species transmission of the virus between humans and animals, and prevent wider zoonotic epidemics
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Strategies for prevention and control of mutant strains

Prevention and control strategies of mutant strains Prevention and control strategies of mutant strains

First, realize active real-time monitoring of the new coronavirus variant strains circulating in the global population, especially focusing on mutations in gene loci related to the pathogenicity and transmissibility of the virus, and timely assess and assess the public health risks of the variant strains.
Warning
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Secondly, according to the changes in antigenicity and drug susceptibility of mutant strains, further optimize the development of vaccines and drugs, and update existing vaccines and drugs; Better vaccine design options
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And explore the vaccine design scheme that can induce good humoral immunity, cellular immunity and mucosal immunity at the same time with better immune protection effect
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In addition, in response to the current vaccination strategy, the protective efficacy of the Delta and Omicron mutant strains has decreased, and it is urgent to adjust the immunization strategy and implement the third dose of immunization to strengthen the immunization
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Finally, comprehensive virus mutation monitoring and vaccine immune efficacy and antibody persistence research, and the development of a dynamic and effective immunization plan, can effectively deal with the possible continued virus mutation
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Cross-species infection of novel coronavirus and novel coronavirus-related virus

Cross-species infection of new crown and new crown-related virus

animal-to-human cross-species transmission

animal-to-human cross-species transmission animal-to-human cross-species transmission

The research on the evolutionary origin of viruses is a long-term process that requires the accumulation of a large number of samples, and requires long-term efforts, resource sharing and international cooperation from countries around the world
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The research on the genetic origin of the new coronavirus aims to reveal the natural/intermediate host and evolutionary path of the new coronavirus, so as to formulate targeted prevention and control strategies and cut off the transmission route of the virus from animals to humans at the source
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After the outbreak, different research teams around the world have successively identified related new coronavirus-like coronaviruses in different species of bats in different regions
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Among them, the new coronavirus-like coronavirus BANAL-52 found in the Malayan horse-headed bat in Laos is the bat-derived coronavirus that is most similar to the new coronavirus in its entire gene, with a similarity of 96.
8%
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The successive identification of new coronavirus-like coronaviruses carried by various bats shows that the new coronavirus-like viruses have extensive geographical distribution, genetic diversity, and a high risk of some viruses infecting people
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In addition, some research teams have also identified a new coronavirus-like coronavirus in Malayan pangolins, which is 85.
5%~92.
4% similar to the whole genome of the new coronavirus, indicating that pangolins may be in the evolutionary path of the formation of the new coronavirus.
one
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It is worth noting that no virus with more than 99% similarity to the whole genome of the new coronavirus has been found, and the evolutionary origin and evolutionary path of the new coronavirus gene are still unclear
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So far, no virus with more than 99% similarity to the whole genome of the new coronavirus has been found, and the evolutionary origin and evolutionary path of the new coronavirus gene are still unclear
.

Human-to-animal cross-species transmission

Human-to-animal cross-species transmission Human-to-animal cross-species transmission

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Animal hosts for natural infection of 2019-nCoV

Animal hosts naturally infected by the new coronavirus Animal hosts naturally infected by the new coronavirus

During the new crown pandemic, the new coronavirus circulating in the human population occasionally infects animals, and even animal-to-animal virus transmission events have occurred
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At present, animals naturally infected with the new coronavirus include: companion animals, animals raised on farms, wild animals in zoos, and wild animals in nature
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Natural and laboratory-infected non-human animal hosts for 2019-nCoV

Natural infection of novel coronavirus and laboratory-infected non-human animal host Natural infection of novel coronavirus and laboratory-infected non-human animal host

The circle near the candle shows the non-human animal host that can infect the new coronavirus in nature; the outermost circle shows the laboratory-proven infecting the new coronavirus or the virus S-RBD protein and the host receptor ACE2 protein.
Binding animal host; the black part represents the undiscovered new coronavirus animal host

The circle near the candle shows the non-human animal host that can infect the new coronavirus in nature; the outermost circle shows the laboratory-proven infecting the new coronavirus or the virus S-RBD protein and the host receptor ACE2 protein.
Binding animal host; the black part represents the undiscovered new coronavirus animal host

Epidemiological survey results speculate that the main reason for animals infected with new crowns is close contact with new crown patients or virus carriers
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In addition, human waste and wastewater may be an important source of infection for the new coronavirus to infect wild white-tailed deer and minks
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Laboratory research on susceptible animals

laboratory research on susceptible animals laboratory research on susceptible animals

Laboratory animal infection tests can evaluate and predict susceptible animals, and establish animal models for new crown research, which is of great significance for epidemic prevention and control and related research
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The binding ability of the new coronavirus to the host ACE2 receptor is one of the most important indicators for evaluating the new coronavirus infection of the host
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The study found that the receptor binding domain RBD of the new coronavirus can bind to ACE2 of 17 different animals.
In addition, laboratory infection experiments found that a variety of animals can be infected with the new coronavirus
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At present, animal models commonly used in new crown research include human ACE2 transgenic mice, hamsters, rhesus monkeys,
etc.

Finding and developing animal models for vaccines and drug efficacy and safety evaluations that can replace non-human primate experimental animals is an important support for the development of vaccines and drugs for the current new crown and future emerging infectious diseases
.

Wu Sen and Bi Yuhai and other research teams have jointly developed a human ACE2 transgenic pig model, which provides a new model for the efficacy and safety evaluation of vaccines and drugs
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The new coronavirus infection model of human lung organs jointly researched by Academician Chen Yeguang and Bi Yuhai's team provides a new and efficient platform for drug effectiveness screening and evaluation
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animal-to-animal transmission

animal-to- animal transmission

The new coronavirus can be transmitted not only from humans to many animals, but also between some animals
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Under natural or laboratory conditions, the new coronavirus can infect a variety of animals, and can transmit intraspecifically in some animal groups.
In addition, cross-species transmission has also occurred in some animals
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However, it has not been found that the new coronavirus can continue to be stable in a certain animal group
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Human-to-animal-to-human cross-species transmission

human-to-animal-to- human cross-species transmission

The transmission of the virus from mink to humans has occurred in the Netherlands and Denmark
.

After the virus was transmitted from human to mink, it mutated in the mink, and the mutated virus was transmitted back to the mink farm workers, resulting in human-to-human transmission
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Strengthening the epidemic and monitoring of the new coronavirus in animals, and preventing the return of new mutant strains to humans, are of great significance to the prevention and control of the new crown epidemic
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Recommendations for monitoring and control of cross-host transmission

Recommendations for monitoring and control of cross-host transmission Recommendations for monitoring and control of cross-host transmission

First of all, it is necessary to actively monitor the infection and epidemic dynamics of 2019-nCoV in animals, and evaluate the genetic variation dynamics, pathogenicity and transmission ability of animal-adapted strains
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Secondly, be alert to the return of the new coronavirus mutant strains circulating in animals to humans, and it is especially necessary to strengthen the periodic health monitoring of the new crown infection status of susceptible animal practitioners, and promptly identify new animal-derived new coronavirus mutants with the ability to infect humans
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In addition, it is necessary to strengthen the disinfection of new crown patients' pollutants and sewage, and prevent and control the spread of the new crown virus from humans to animals
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