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New Research Coronavirus may have Hidden Spread among people before large-scale outbreaks

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Before the large-scale outbreak, the new coronavirus may have experienced “recessive” transmission in the population for some time. In the early stages, the infected person was asymptomatic, mildly symptomatic, or sporadic cases of pneumonia were not noticed until the virus acquired a key point mutation To better adapt to human hosts.

Fudan University Public Health Clinical Center Professor Zhang Yongzhen and collaborator Professor Edward Holmes of the University of Sydney published an article in Cell on March 26, revealing the genetic data of the virus to tell people the truth and people about the outbreak The cognitive divide of origin.

The article also proposes that the new coronavirus may be a recombinant virus, and its high replication rate makes the mutation rate of the gene seem negligible, but it should still pay enough attention.

Viruses Need 20 years to evolve from strike to Human


The author of this paper reviewed the previous traceability of New Coronavirus and pointed out that the closest match to the new Coronavirus gene sequence is the coronavirus found in the Yunnan strike, which is more than 1,500 kilometers away from Wuhan. “The simple inference from this is that our sampling of strike viruses has a strong bias against certain geographic locations. This needs to be corrected in future studies,” said the study authors.

Even though the sequence similarity between the coronaviruses of the aforementioned Yunnan strike and the new coronavirus reaches 96% -97%, this may represent more than 20 years of evolutionary sequences.

The article concludes: “It cannot be ruled out that before the virus was first discovered in December 2019, the virus acquired some key mutations during the ‘recessive’ transmission in the population.

For the virus to have a strong adaptive evolution in humans, it is necessary to obtain mutations at key RBD sites, as well as insertion mutations at the Furin protease cleavage site-specific to the new coronavirus.

The authors speculate that the virus may have spread to the human population for some time before it broke out quickly in a short time, and it adapted well to human hosts.

During the early “recessive” transmission, when the virus was first transmitted to humans, it might not have been detected due to asymptomatic infection (only minor respiratory symptoms but no pneumonia), or some small-scale local outbreaks of infection were not Report to the standard system.

In the continuous human-to-human process, the virus gradually evolved key mutations such as the protease cleavage site and became fully adaptable to humans.

To verify whether the above speculation is correct, the researchers believe that back-tracking samples of patients with respiratory symptoms before December 2019 may help to unravel the mystery of how the virus “recessively” spreads, but also raised the difficulty of this work.

Retrospective serological or metagenomic studies of respiratory infections will help determine whether this is correct, although such early cases may never be detected,” the authors said.

Another issue of great concern pointed out in the paper is whether the new coronavirus is a recombinant virus. The reorganization of the virus will accelerate the large-scale outbreak of the epidemic, so it should not be underestimated.

However, trying to determine the exact pattern and genomic origin of recombination events is difficult. “Especially because many recombination regions may be small, and as we sample more new corona-associated viruses, small mutations may have occurred.” The authors said. To address these issues, the authors believe that it is necessary to take a wider sample of virus diversity in animal populations, but this is equally difficult.

Unfortunately, there is a clear lack of direct animal samples in the South China seafood market, which may mean that it is difficult or even impossible to accurately identify any animal hosts in this place,” the authors said.

The authors also call for the simplest and most cost-effective way to reduce the risk of future outbreaks, given the enormous diversity of viruses in wildlife and their ongoing evolution, to limit our exposure to animal pathogens as much as possible.

Low virus mutation rate may be an Artifact


With the epidemic of COVID-19, more viral genomes were sequenced. The authors suggest that although the mutation rate of the new corona currently looks low, it may be masked by the virus’ high replication rate in the host.

It is still unclear whether the virus’s ability to mutate will affect the virus’s transmissibility and toxicity. Therefore, in the current situation of large-scale transmission, it is necessary to continue to pay attention to the virus mutations that cause phenotypic changes.

The earliest virus samples in Wuhan contained less genetic diversity. These virus samples all share the same modern common ancestors, which may hinder detailed phylogenetic and phylogenetic inference of virus evolution. Nevertheless, the author believes that the Wuhan Public Health  Department did an excellent job of identifying the first cases of pneumonia.

Although the accumulation of genetic diversity means that it is now possible to detect phylogenetic clusters of different coronavirus sequences.

It is difficult to determine by genome comparison alone whether the virus has immobilized important phenotypic mutations when it spreads in a global population, any such The claims need careful experimental verification.

Considering the high mutation rate of RNA viruses, researchers believe that more mutations will appear in the viral genome. “This will help us track the spread of the new coronavirus. However, as the epidemic spreads, our sample size of the sequence relative to the total number of cases may be so small that it is difficult to detect a single chain of transmission. Therefore, we are trying to infer the exact Always be cautious when it comes to spreading events. “The authors said.

Zhang Yongzhen and Prof. Holmes published the complete genome sequence of the first new coronavirus to the world on the open virology website as early as January. This virus came from a patient with unknown pneumonia admitted to Wuhan in late December. At present, there are about 200 new coronavirus genome sequences released from patients from many regions of the world.

The authors also point out that with the rapid spread of global coronaviruses, a reference to the number of confirmed cases should be avoided, as mild or asymptomatic infections are often excluded from the count, and the true number of cases is likely to be much larger than reported.

Besides, although there is no large-scale serological survey, these uncertainties may not be resolved, but from the current data, the mortality rate of the new corona disease may be higher than seasonal influenza, but lower than SARS and MERS viruses.

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