The rising infection rate intensifies the fear of virus mutation, and experts suggest that it should be continuously monitored.

"As an RNA virus, COVID-19 will produce many variants every time it spreads. The faster the epidemic spreads, the higher the chance of mutant strains. Therefore, for China, the moment is a time point that needs special attention to virus mutation. " Lu Ji Meng, a German virologist of Chinese descent and a professor at the Institute of Virology, Essen University School of Medicine, said in an interview with China Newsweek.

"In the process of virus replication and spread, mutation is a natural process that happens constantly. Some mutations enhance the transmission ability of the virus, some mutations escape immune recognition, and some mutations have no obvious effect on the biological activity of the virus. At present, whether the widespread spread of COVID-19 in China will lead to new mutations, especially the impact on its immune escape ability and pathogenicity, is a key issue of great concern to the whole society. " Zhang, director of Tsinghua University Global Health and Infectious Diseases Research Center, stressed.

65438+On February 27th, the joint prevention and control mechanism of the State Council released the Monitoring Plan for Type B and Type B Infection in novel coronavirus. In terms of virus mutation monitoring, the document points out that all localities have carried out genome-wide sequencing in COVID-19 for some immigrants from land, air and port cities, patients from sentinel hospitals, key places and key populations, and samples of severe cases and deaths, and submitted the sequences to the Institute of Virology of China CDC on time.

Many virologists said that in such a high-intensity transmission environment in China, it is almost certain that the virus will mutate. But the question is, in which direction will the virus mutate? How should China strengthen the monitoring of virus variation and fight a "prepared battle"?

When the number of infected people increases sharply, we should be alert to mutant strains.

Virologist Lu said that at present, new mutant strains have appeared in all continents of the world. In the past, because there was no major epidemic in China, all strains were imported from abroad. However, with the loosening of prevention and control measures, in China with such a huge population, it is possible to produce new virus variants.

Xu Wenbo, director of the Institute of Virology, China CDC, recently pointed out that Omicron appeared from 202 11,and by February 2022 18, it had evolved from five branches of BA. 1 to 709 subfamilies of BA.5; XBB is one of 72 strains produced by recombination among these subfamilies. "So, the variation of Omicron will continue. As long as it circulates in the crowd, it will copy and copy will mutate. " He said.

On February 23, 2022, at 65438, Kang Hua Hospital, Xinpu New District, Zunyi City, Guizhou Province, medical staff prepared for vaccination. Photography/reporter Qu Honglun

Lu stressed that this does not mean that after everyone is infected once, COVID-19 virus will not continue to spread and mutate. The virus will continue to spread among people with low immunity, such as the elderly who have not established enough immune barriers. At this time, in order to gain the spread advantage, the virus can easily screen out some variants with stronger escape ability. Wang Guiqiang, director of the Department of Infectious Diseases of the First Hospital of Peking University, recently said that for most people with normal immunity, effective immune antibodies will appear in people within six months; However, if new mutants appear or new subfamilies show strong immune escape ability, it may lead to reinfection.

Liu Shan, a virologist at Ohio State University in the United States, explained to China Newsweek that the variation of RNA virus is caused by external selection pressure, including host immune system pressure and treatment pressure, in addition to its own internal factors. Therefore, in order to escape these pressures, viruses must constantly evolve, which is an inevitable result, and there is no need to panic.

"There is a balance between the virus and the host, and the spread and pathogenicity of the virus are generally opposite." He pointed out that from the law of virology, most mutations are to escape immunity. However, too many mutations can also lead to the virus losing its function and even extinction. So there are also some mutations to restore its function and ensure its infectivity. In fact, Lu said, scientists found that every time COVID-19 mutates, the viral load in respiratory epithelial cells is higher, and the ability of viral fusion cells is enhanced.

Liu said that it can be observed that under the rapid spread, the mutant appeared in Omicron faster and faster, but the overall pathogenicity has not been greatly improved so far. In September this year, 80% of the infected people in the United States were BA.5. However, only three months later, in the United States, the proportion of BQ. 1, Bq.1,XBB is getting higher and higher, while the proportion of Ba.5 has dropped below 10%.

The pathogenicity of the virus needs continuous monitoring.

According to the latest report of Bloomberg News on February 25th, 65438, the data of the global COVID-19 gene sequence database GISAID showed that the virus strains that promoted the wave of China infection were all known internationally, and there was no evidence that new mutant strains were produced.

Last month, China CDC submitted 25 new gene samples from Beijing, Inner Mongolia and Guangzhou to GISAID. Judging from these sequences, no significant mutation has occurred. Specifically, the recent epidemic in Inner Mongolia was caused by the BF.7 variant and then spread to Beijing. Since June, 65438+October, 2022 10, an independent epidemic broke out in Guangzhou, and the imported mutant was the earlier BA.5.2 family.

Recently, there are rumors on the Internet that Delta and Omicron are popular in some parts of China. Xu Wenbo responded to this. According to the real-time dynamic monitoring, no Delta mutant was found in China, and no recombination between Delta mutant and Omicron mutant was found. From the beginning of 65438+February to the present, 9 epidemic subfamilies in COVID-19 have been detected in China, all of which belong to Omicron mutant strains.

What will COVID-19's variant look like in China? Some analysts believe that one possibility is that Omicron and its hundreds of subtypes will occupy the population, leaving no room for other varieties to spread-just like the global Omicron epidemic in 2022, the immunity established by vaccines and natural infections will eventually make people's antibodies enough to resist serious diseases.

Xu Wenbo pointed out that the hospitalization, death and severe cases caused by Omicron were significantly lower than those caused by early Delta strains and other "noteworthy variants", and no significant increase in severe cases and deaths was observed among more than 700 virus strains. Generally speaking, it is unlikely that Omicron will become a mutant with obviously enhanced pathogenicity.

Michelle, director of the National Laboratory of Virology of Wuhan University, said in an interview with China Newsweek that so far, the "noteworthy mutants" that are popular or have been popular all over the world are usually not evolved from the previous dominant mutants. On the contrary, they come from different strains. Delta was first discovered in India and quickly swept the world, causing an epidemic. After Omicron 202 1 appeared in South Africa at the end of the year, it quickly replaced Damei. Omicron did not evolve from Delta.

In terms of pathogenicity, although in the long run, in order to obtain adaptability, the virulence of the virus will tend to decrease with the emergence of more mutations caused by immune escape, but this is not absolute. Michelle pointed out that the future mutation in COVID-19 is "unpredictable" and needs continuous monitoring.

In 20021year, the popularity of Damei brought great pressure to the German medical system. Lu said that the median age of early death caused by COVID-19 strain was 82 years old, but by the peak of Delta, the median age had dropped to 74 years old, and some young people were seriously ill. In other words, the Delta mutant is more lethal than its predecessors.

Another reason that the current epidemic situation in China aggravates the concern of virologists around the world is that most people in China have never been infected with COVID-19 before, and the low immune barrier is more conducive to the virus to escape mutation.

Liu Shansi explained that although the virus is also facing immune pressure, there are still quite a few people in China who have not been vaccinated or have been vaccinated for a long time and are not infected with the virus. Especially people with low immunity, such as cancer patients, organ transplantation, AIDS, etc. Due to the poor immunity of the host, the virus does not have the strong pressure of rapid mutation, but will slowly evolve in a hidden way, accumulate some natural mutations, or recombine the virus and appear some brand-new mutant strains.

In fact, it has been reported in the literature that the South African strain prevalent in 2020 may appear in these patients. The Omicron strain was not detected before and suddenly appeared. Before its birth, it may have been "brewing" for months or even a year.

On June 5438+February 2 1 day, 2022, people were waiting in line in Shengtai Community, Jiangning District, Nanjing City, Jiangsu Province. On the same day, Jiangning District 16 fever mobile medical vehicle drove into residential areas and enterprises to provide convenient medical services for the masses. Figure/people's vision

How to monitor virus variation?

"If you don't do gene sequencing, you are basically fighting a war without intelligence." In the spring of 20021year, when the epidemic caused a tsunami in India, Ashish Jaha, dean of the School of Public Health of Brown University and professor of the School of Public Health of Harvard University, pointed out that the lack of monitoring and early warning of virus mutation became one of the main "pushers" of the epidemic in India at that time.

Zhang, director of the Center for Global Health and Infectious Diseases Research in Tsinghua University, told China that the monitoring of virus variation helps to understand the genetic characteristics and molecular epidemiological characteristics of the virus; On the other hand, it can provide the most realistic and real goal for timely evaluation of existing vaccines and drugs. The research and development of monoclonal antibody drugs and vaccines should be based on the gene sequence of the virus.

On February 20, 65438, Xu Wenbo, director of the Institute of Virology of China CDC, introduced at the press conference of the joint prevention and control mechanism of the State Council Office that after the adjustment of the prevention and control strategy of COVID-19 epidemic, the Institute of Virology of China CDC formulated the Work Plan for Monitoring Mutants in COVID-19, China. According to this scheme, three cities in each province, each city 1 sentinel hospital and each sentinel hospital are required to take samples of 15 emergency cases, 10 severe cases and all deaths every week for genome sequencing and analysis, and upload the sequencing data to the Institute of Virology of China CDC within one week to establish the national COVID-19 genome database.

Through the implementation of this program, Xu Wenbo said that it is possible to dynamically monitor the epidemic dynamics of COVID-19 Omicron series mutants in China and the composition ratio of each subtype in real time, and find new mutants with potential biological characteristics, including clinical manifestations, transmission and pathogenicity, which can provide scientific basis for vaccine development and diagnostic reagent evaluation, including nucleic acids and antigens.

In 1990s, Liu Shanwei studied and worked in the Institute of Virology of China Center for Disease Control and Prevention. Liu Shansi thinks this monitoring scheme is a great progress and a good start, but he also puts forward some suggestions. Monitoring posts should be more widely distributed. There are only three cities in each province, which may not represent all kinds of situations in urban and rural areas. China has a wider range of sequencing capabilities.

On the same day, the joint prevention and control mechanism of the State Council released the "Epidemic Monitoring Plan for novel coronavirus Infection", proposing that all localities should rely on sentinel hospitals of the national influenza surveillance network to carry out novel coronavirus infection monitoring. It is necessary to report the complete gene sequence of the virus mutant to the Center for Disease Control and Prevention of China in time. The number of outpatients and inpatients, the number of patients with acute fever and respiratory symptoms, the number of people infected with COVID-19 and the variation of virus strains were dynamically analyzed.

At the beginning of 20021,the United States stipulated to sequence the virus samples of 5% confirmed cases; In September and June, 2022, COVID-19 infection cases of 15% and 13% were sequenced in California, USA, which were distributed in both urban and rural areas. "The United States can calculate that it is not necessary to limit 10 or 15 cases. If it is random sampling, the data will be more valuable. " Liu Shansi said. Some insiders also believe that considering that a large number of infection cases will not be reported, only a higher proportion of nucleic acid test samples can be sequenced to represent the actual epidemic situation of the current virus strain.

Liu Shansi believes that the sampling and analysis of people with low immunity should not be ignored in the future. In addition, he suggested that from the research in North America and Europe, many animals were infected with COVID-19, so we should not neglect the quarantine of animals and the monitoring of transmission modes.

Equally important, many scholars pointed out that gene sequence samples collected from clinic should be combined with epidemic trends and patient symptoms to study the possible spread and pathogenicity caused by these mutant sequences. Michelle also stressed that it is necessary to evaluate the virulence of mutants scientifically and comprehensively, which requires the cooperation of clinical, public health and laboratory research.

Published in China Newsweek magazine,No. 1075, 2023. 1.2.

Magazine title: Will the virus mutate faster as the infection rate rises?

Reporter: Peng