In response to the problems of public concern, the Global People reporter interviewed Wu Guizhen, chief scientist of biosecurity of the Chinese Center for Disease Control and Prevention, and Wu Zunyou, chief scientist of epidemiology, to interpret the characteristics of the Delta mutation and the key to prevention and control.
| Author: Yang Xueyi
On July 20, 2021, the Nanjing Municipal Health Commission issued a notice that among the regular nucleic acid test samples of Nanjing Lukou Airport staff, there were positive test results, involving staff mainly involved in the support personnel involved in airport flights. Cases of infection directly related to Nanjing Lukou Airport have been found in many parts of the country, among which the Zhangjiajie "Charm Xiangxi" performance and the Yangzhou chess and card room once became the eye of the epidemic storm. On July 30, Zhengzhou, which had just experienced extreme rainstorms, found a case of asymptomatic infection of the new coronavirus in the Erqi District, and successively found new infected people, and after circulation investigation, most of the infected people were related to the sixth hospital of Zhengzhou. It was later confirmed that the epidemic in Zhengzhou was not directly related to Nanjing Lukou Airport.
After the genome sequencing of specimens of confirmed covid-19 cases in many parts of the country, it was confirmed that it was the Delta variant strain that triggered the current outbreak. On August 5, the joint prevention and control mechanism of the State Council held a press conference, and He Qinghua, a first-level inspector of the Disease Control Bureau of the National Health Commission, said that from the current situation, the overall situation of this round of epidemic situation is controllable. However, due to the large scope of the current round of epidemics, the wide range of people, and the superposition of local epidemics caused by imported cases from multiple different sources, the arduousness and complexity of the entire epidemic prevention and control have increased, but as long as various prevention and control measures are strictly implemented in various places, the epidemic can be basically controlled in two to three incubation periods.
Left: Wu Guizhen was interviewed at the Institute of Microbiology of the Chinese Academy of Sciences on July 9 (photo by reporter Zhang Yan) Right: Wu Zunyou at the press conference
Deciphering one: How contagious is Delta?
"An important measure of viral transmission is the regeneration index or spread coefficient (r0), which is how many people each patient can infect on average. Last spring and summer, the spread coefficient of the new crown virus averaged 2-3 people. The currently popular Delta variant strain, with a spread coefficient of 5-8 people, increased by 2-3 times. Wu Zunyou analyzed, "Therefore, the Delta mutation is by far the fastest spreading mutation." ”
"The Delta strain of COVID-19 was first detected in cases of COVID-19 reported in India in September 2020." Wu Guizhen introduced that since the outbreak of the new crown pneumonia epidemic, mutant strains have been found in many countries such as the United Kingdom, South Africa, Brazil and India, and WHO has divided them into "variant of concern" and "concern of interest" (voi) according to their different transmissibility and pathogenicity. Compared with earlier reference strains, the mutant strains of concern cause or potentially cause changes in viral phenotype and spread in communities, or in multiple regions and countries. Concerned that harmful changes in the characteristics of mutant strains such as increased transmission or epidemic, increased pathogenicity or increased clinical manifestations may also lead to a decrease in the effectiveness of public health measures, social measures and existing diagnostics, vaccines and treatments. Wu Guizhen said that WHO included the Delta variant as a strain of concern on May 10 this year.
Wu Zunyou said that in addition to the Delta variant found in India, the alpha variant found in the United Kingdom, the beta variant found in South Africa, and the gamma variant found in Brazil were all included in the WHO's concerned variants. Currently, four more variants are identified by WHO as concerned strains, characterized by "the possibility of developing into highly valued variant strains, or they may be naturally phased out during epidemics".
Wu Guizhen recalled that as early as last year, when the Delta mutant strain spread widely in India, the industry generally had a premonition that this mutant strain would become the main dominant strain in a short period of time and ravage the world. At present, the Delta variant strain has become endemic in more than 130 countries and regions around the world.
June 22, 2021, Gurgaon, India. Last September, the Delta strain first appeared in a reported case of COVID-19 in India.
Deciphering Two: How did Delta spread?
Wu Guizhen introduced to reporters that the new crown virus is an RNA (ribonucleic acid) virus, there is a spike-like S protein on the capsule membrane, and the receptor binding domain (RBD) is at the head position of the S protein. Viruses invade human cells, requiring receptor binding domains and human cell receptor ace2 binding, and after entering the cell, RNA begins to replicate wildly. Once the viral components produced in human cells are assembled into new intact viral particles, they leave the human cells and invade the next cell. The mutations that occur in the Delta strain allow it to better invade and release human cells.
Wu Zunyou pointedly said that the mutant strain appeared at the location of the spike protein more than 10 mutation sites, these mutations make the virus more likely to infect human cells, and can replicate more viruses more quickly after infection. Wu Guizhen further analyzed that the Delta variant has 3 important mutations in the receptor binding domain, which is the key to accelerated transmission. These 3 mutations can increase the affinity of the viral receptor binding domain to the human cell receptor, and at the same time facilitate the faster release from the infected cells after the virus invasion is completed. "That's why the Delta variant has quickly become a major epidemic strain in India and around the world." Compared with the original strain, the Delta strain has the characteristics of fast transmission speed, fast internal replication, and long negative transition time, which is due to the mutation of some of the above key sites of the virus. ”
However, "according to relevant scientific research and epidemic prevention and control practices at home and abroad, the Delta variant has not led to subversive changes in the biological characteristics of the new coronavirus, its source of infection and transmission route are basically clear, and the existing epidemic prevention and control measures are still effective for the Delta variant." Wu Guizhen said.
On August 8, 2021, at a testing point in Jiangning District, Nanjing, medical staff conducted nucleic acid testing samples for residents.
Decryption three: is the new crown virus mutating fast?
"Compared with DNA (dna ribonucleic acid) viruses such as herpes virus and hepatitis B virus, RNA viruses are more likely to mutate." Wu Guizhen said that this is due to the lack of a polymerase with correction errors in the RNA virus, so when replicating in human cells, the errors that occur cannot be corrected in time. Based on this, RNA viruses are more likely to mutate and are more frequent. "In fact, the genome of a virus mutates all the time during its replication process. Most of these mutations are harmful and lethal to the virus itself, and only a few mutated viruses survive. ”
Wu Zunyou summarized several situations of virus mutation to reporters. "Some of the viruses that cause serious infectious diseases in humans rarely mutate, such as smallpox; some viruses appear with certain regular mutations, such as influenza, and the mutation may have a certain periodicity; and some viruses, mutations without obvious laws, especially rna viruses, such as HIV. The new coronavirus is also an RNA virus, and so far, its mutation law has not been summarized. ”
But Wu Guizhen believes that the mutation rate of the new crown virus is not fast, "only about half of the flu virus, 1/4 of the HIV." For example, she said, in the new coronavirus, about 30,000 bases of the RNA genome will appear only about two base mutations per month. Since the coronavirus has been raging around the world for a year and a half, some mutations have inevitably accumulated.
Deciphering Four: What is the trend of virus mutation?
"There are only two viruses that have been completely eliminated by humans, smallpox virus and rinderpest virus." Wu Guizhen said that the virus has actually been seeking a balance with humans and the natural world, "when the virus invades the host, it will cause damage to the host cells, which is the pathogenicity of the virus, that is, the virulence." From an evolutionary perspective, in the constant genetic mutation, the host infected by those highly virulent offspring viruses will die quickly, resulting in the interruption of the chain of transmission and elimination. Hosts infected with weaker offspring viruses survive longer and have a greater chance of transmission. Therefore, a relatively 'perfect' virus has the characteristics of high transmission and low lethality. Therefore, the virus is also following the law of "natural selection, survival of the fittest", "It is generally believed that the virus mutation has a trend of 'weakening virulence and increasing transmissibility', and the ultimate purpose of the virus is not to kill the host, but to 'live' and expand its own 'territory', which can only be achieved through more host transmission." ”
Wu Guizhen said that the current mutation of the new crown virus may also have the above trend. "Studies by the Guangdong Provincial Center for Disease Control and Prevention show that the Delta variant has a viral load of 1260 times higher than the original strain, and patients have been contagious for longer. But even so, delta strains are predominantly mild, asymptomatic, and common, with fewer severe cases and lower fatality. "At the same time, the clinical symptoms of patients infected with the Delta strain are atypical, some only show fatigue, olfactory disorders, or mild muscle soreness, and a considerable number of patients have no symptoms." However, the biological characteristics such as the immunogenicity of the Delta strain have not undergone subversive changes, and the existing epidemic prevention and control measures, including vaccines, are still effective for the Delta strain. Its transmission ability is very strong, but its pathogenicity is far inferior to that of Ebola and SARS. Wu Guizhen stressed again.
Wu Zunyou said that the best way to reduce and control the mutation of the virus is to control the spread of the new crown epidemic around the world. "As long as the outbreak is under control, the virus has no chance to spread from person to person, and there is no chance of new mutated strains."
Deciphering Five: Are the previous prevention and control measures still effective?
"After the emergence of the epidemic in Nanjing, we have strengthened prevention and control measures in a timely manner, strengthened monitoring and testing, and controlled the epidemic situation to a minimum; at the same time, the scope of vaccination in China is still expanding, effective prevention and control strategies coupled with high vaccination rates, we are confident that in the near future to control the spread of Delta variants in China, so there is no need for everyone to worry too much." Wu Guizhen is very confident in the control of this wave of domestic epidemics.
However, the epidemic of the Delta variant has led to the emergence of some infected people in the country who have been vaccinated, that is, "breakthrough infection". Wu Zunyou explained that in order to develop a vaccine to control the virus, the human immune system must produce antibodies that inhibit the replication of the virus after the virus infects the human body, that is, neutralizing antibodies. If neutralizing antibodies cannot be produced, or if neutralizing antibodies do not control the replication of the virus in the body or prevent reinfection, then a vaccine cannot be developed, and this is the case with HIV for the time being. The effectiveness of the vaccine is indeed related to whether the virus mutates, "if the virus does not mutate, the vaccine effect is the best; if the virus only has a very small mutation, the protective effect of the vaccine will not have much impact; if the virus is very variable, the main structure and nature change, then the protective effect of the vaccine may be greatly weakened, or the vaccine loses its protective effect." ”
"Regarding the mutation of the new crown virus and the impact of the mutation on the effectiveness of the vaccine, the Ministry of Science and Technology of the People's Republic of China has set up a special project to organize a team of scientists to conduct research. It is difficult to predict the mutation of the virus, but under the premise of ensuring strong and orderly prevention and control, we should do a good job in monitoring the virus mutation and continue to carry out basic scientific research, and once we find unfavorable signs of mutation, we will implement isolation intervention as soon as possible to control the mutation strain at an early stage. Wu Guizhen said that some time ago, China successfully blocked the spread of the local epidemic in the Delta variant that occurred in several densely populated and mobile cities in Guangdong Province, proving that measures such as vaccination, wearing masks, washing hands frequently, maintaining social distancing, and avoiding crowd gatherings are effective.
Deciphering Six: What is an effective weapon to defeat Delta?
Wu Guizhen said, "The new crown virus has only one serotype, and the existing mutant strains, including the Delta variant, are antigen drift that occurs within a serotype, as long as the mutation does not break through the restrictions of the serotype, the existing various technical routes of the new crown vaccine will definitely have a preventive and protective effect." ”
There are many reasons for the "breakthrough infection", "one is that the protective efficacy of existing vaccines is difficult to reach 100%; the second is that even if the vaccine with the best protection efficacy, individual differences will lead to 'breakthrough infection' in individuals with low immune response; third, the length of vaccination time, the dose of virus exposure and the mode of exposure will affect the protective effect of vaccines to a certain extent." Wu Guizhen said that even if there is a "breakthrough infection", vaccination is still urgent. "From an individual level, in addition to preventing infection, vaccines can also reduce the incidence of severe illness and death after infection; from a group perspective, although the new crown vaccine cannot protect all people from infection, according to the current protective efficacy, reaching a certain vaccination rate can establish an immune barrier, prevent the large-scale outbreak of the new crown virus in the population, and also reduce the burden of disease." Therefore, active vaccination and maintaining a high vaccination rate are of great significance for the future full opening up of society, ending the new crown virus pandemic, and maintaining the normal operation of the medical and health system, and are also the prerequisites for the normalization of social and economic activities and people's lives in the future. ”
Vaccination also plays an important role in controlling viral mutations. "The more opportunities a virus has to spread widely among people, the more opportunities there are to replicate and the more likely it is to mutate." Therefore, the first is to speed up vaccination and increase the proportion of vaccinated people; the second is to quickly isolate the exposed population through circulation after the discovery of cases, which is like building a dam in the process of 'flood overflow' of virus transmission, so as to control the spread of the virus and the mutation of the virus within a certain range, providing time for the final victory over the epidemic. Wu Guizhen said.
At present, various studies on the mutation of the new crown virus are also in progress. Wu Guizhen introduced that in the biosafety tertiary laboratory (p3 laboratory) of the Institute of Virology of the Chinese Center for Disease Control and Prevention, through the cross-neutralization experiment of the people who have been vaccinated with the Chinese biological inactivated covid-19 vaccine and multiple new coronavirus variants, it was found that the Chinese biological new crown vaccine can achieve cross-neutralization of four concerned variants, including the Delta variant. That is, China's biological COVID-19 vaccine can still provide effective protection. A number of units, including the Institute of Viral Diseases of the Chinese Center for Disease Control and Prevention, have successfully isolated multiple Delta variants, and will evaluate the strains in strict accordance with the quality requirements of human vaccines and screen for vaccines.
At the same time, the existing COVID-19 vaccine research and development strategy has also matured. The Institute of Viral Diseases of the Chinese Center for Disease Control and Prevention is cooperating with the Beijing Institute of Biological Products of China Biologics and other units to carry out research and development of beta variants and Delta variants as seed strains of the new crown vaccine. The vaccine research and development of the mutant strain can be relatively faster than the original strain vaccine, "drawing on the research and development and production mode of influenza virus vaccines, replacing the strains or key antigen components in them, which will greatly improve the research and development efficiency of new vaccines and timely use them for the prevention and control of new variant strains."
On March 25, 2021, the anti-epidemic science and technology research team of the Institute of Microbiology of the Chinese Academy of Sciences is carrying out relevant experimental research.
"What should we focus on next?" The Global People reporter asked. Wu Guizhen said that first of all, we must do a good job in the normalization of the prevention and control of the new crown pneumonia epidemic and accelerate the promotion of new crown virus vaccination, which is the key to establishing the immune barrier as soon as possible. Second, it is necessary to further strengthen scientific research and the research and development of vaccine drugs, and study vaccines with higher protection rates and a wider range of protection, including generic vaccines against new coronavirus mutant strains and even other coronaviruses that can infect people. Third, normalizing the prevention and control of the epidemic is indispensable, which is necessary to deal with sporadic local sporadic cases caused by imported epidemics. In order to reduce the number of sporadic cases, on the one hand, through international vaccination recognition and nucleic acid negative certification, the possibility of imported cases is reduced; at the same time, it is necessary to strengthen surveillance, detect cases early, do a good job of flow adjustment and nucleic acid testing of key populations, accurate prevention and control, and quickly extinguish the epidemic. Finally, it is important to continue to advocate for effective non-pharmacological interventions in everyday life, such as wearing masks, washing hands frequently, maintaining social distancing, minimizing going to crowded places, and making them a new normal. "Numerous studies have shown that these simple and easy measures can significantly reduce the spread of infectious diseases."
Source: Global People
Editor: Zhang Heng, Lv Ruitian, Xie Peng, Chief Editor Li Meng