The science and politics of "group immunity"

China News Weekly reporter / Huo Siyi

Issued in the 943th issue of China News Weekly, 2020.4.13

In the first week of April, the world did not get better.

On the evening of April 5, British Prime Minister Boris Johnson spent the first weekend of the month in the hospital, ten days after his diagnosis. His doctor described it as a "preventive measure", although Boris has shown persistent fever. But on Monday afternoon a few hours later, his condition began to deteriorate, and he has now been transferred to the intensive care unit of the hospital, where Foreign Minister Dominique Rab is temporarily acting as prime minister.

On April 4, Graham Medley, a professor of epidemiological models at Imperial College London and a senior adviser to the Johnson administration, suggested that the UK should reconsider whether to adopt a "group immunization" policy. He said: "The only viable way to help us through this emergency health event is to make people infected and therefore no longer vulnerable."

He warned that the "blockade" policy that the UK is adopting has "driven the whole country to the corner". If this continues, it will have a more serious negative impact than the new crown virus-the economy will fall into a total collapse. In his view, the blockade only won some time and prevented the short-term spread, but did not solve any problems. Medley pointed out that on April 13, the Prime Minister will make a "major decision" to determine whether the blockade policy will continue.

After Patrick Valence, the UK ’s chief scientific adviser, first proposed the concept of “group immunization” on March 13, experts and media criticized a popular pessimism argument that if an effective vaccine has not been effective After birth, in the next 1 to 2 years, "group immunization" is an inevitable result of passive formation even if it is not a actively selected strategy.

A recent study published by the University of Oxford in the UK seems to have advanced this result. After conducting the model deduction, the researchers concluded that as of March 19, 36% to 68% of the people in the UK may have been infected with the new corona virus; Italy may have 60% to 80% of the people infected with the new corona virus by March 6 . This means that Britain and Italy may have formed a practical "group immunization".

This is just a model-based speculation, which needs to be confirmed by more accurate testing. However, if countries such as Europe and the United States will achieve "group immunization" in the future, for countries such as China that have adopted strict control measures, because most people are not infected and lack immunity, a "vaccination gap" will be formed, which is a very dangerous signal of.

"68% of British people already infected is the most extreme result"

On March 24th, the Oxford University Infectious Disease Evolutionary Ecology team published a study that used the new crown death case data reported by the United Kingdom and Italy to simulate three different scenarios by giving different parameters to derive the possibility of the United Kingdom and Italy. The actual number of people who have been infected with the new coronavirus.

In the first two simulation scenarios, the setting of "the proportion of high-risk susceptible people in the population" is the same, which is 1%, that is, one out of 100 people is an elderly person over 65 or has a serious underlying disease, or breathing after infection Patients with serious complications such as failure. But in the first scenario, the basic number of infections (R0) is set to 2.25, that is, an infected person can infect 2.25 people. It is estimated that as of March 19, at least 36% of the British people have been infected with the new crown virus. In the second scenario, the R0 value is increased to 2.75. In the model, the proportion of British people infected with the new coronavirus has also risen to 40%.

The third scenario sets the high-risk susceptible population to 0.1%. According to the model, death cases are a small part of the high-risk susceptible population, so given the number of deaths, the lower the proportion of the high-risk susceptible population in the population, the greater the base of infection of the population. In this case, even with the smaller R0 value of 2.25, at least 68% of the British people have already been infected. In this regard, Paul Kellerman, one of the researchers and a professor of virology at Oxford University, said: "68% of the British people have been infected is the most extreme result."

The same is true in Italy. According to the above three different parameter settings, it can be concluded that as of March 6th, 60% to 80% of the people in Italy may be infected with the new crown virus.

To verify the accuracy of the model, the researchers simulated the cumulative number of deaths in the UK and Italy within 15 days after the first death case. The results found that the results of the three scenarios were very consistent with the increase in the cumulative death case data of the two countries. Therefore, the study points out that Britain and Italy may have accumulated sufficient levels of group immunity.

But Simon Gerbins, professor of infectious biology at the Bright Laboratory in the United Kingdom, pointed out that this does not mean that more than half of the people in the United Kingdom have been infected with the new crown. The third most extreme situation is based on high-risk susceptible people. The assumption is only 0.1%. Once this number becomes 1%, the number of infections has dropped a lot, only 36% ~ 40%. "But the point is that no one knows what the proportion of high-risk people is."

According to Paul Hunt, a professor of pharmacy at East Anglia University, it is too early to make such an assumption. This ratio is related to the age distribution of the population, the proportion of people with basic diseases and the closeness of social connections in a society, and these will continue to change with the development of the epidemic.

A recent report published by the Kaiser Family Foundation, a nonprofit research organization that has long been concerned about public health policies, pointed out that in the United States, about 37.6% of adults over the age of 18 will experience serious symptoms after being infected with the new coronavirus. This is equivalent to 4 out of 10 people belonging to high-risk susceptible groups. In addition, this ratio is different in different states, in the highest West Virginia, it can reach 49.3%, and in the lowest Utah, it is also 30%. The study defines high-risk susceptible populations as: elderly people over 65 years old, and people between 18 and 64 years old with heart disease, chronic obstructive pulmonary disease, uncontrollable asthma or diabetes. The above figures are very different from the parameters set in the paper.

The setting of R0 also faces the same question. The WHO believes that the basic infection number of the new coronavirus is 1.4 to 2.5, and the median is 1.95. But the latest report, which combines 12 related studies, shows that the more appropriate R0 should be 3.28, with a median of 2.79. Throughout March, with the rapid spread of the epidemic in continental Europe, the Imperial College ’s epidemiology team raised their estimates of R0 twice, the first time on March 26, setting the range of R0 values. It was set at 2.4 ~ 3.3, and after four days, it was increased to 3 ~ 4.7 again.

In addition to the problem of parameter setting, the biggest problem of this model in the view of Gerbins is the assumption that the United Kingdom and Italy are an absolutely homogeneous population settlement, that is, different groups in different regions can be exposed to the virus absolutely equally. And infect others.

Zeng Guang, the chief epidemiologist of the Chinese Center for Disease Control and Prevention, told China News Weekly that the population is very complex and unbalanced. For example, within Italy, the differences in infections between different regions are very different. Hunt also pointed out that the ability of asymptomatic, mild and severe patients to transmit the virus to others is different. This model does not take into account these differences. "This will cause an overestimation of the virus infection rate, which will affect the estimation of the actual infected population."

Giuseppe Remuzi, a well-known nephrology professor in Italy, pointed out to China News Weekly that it is impossible for more than 60% of people in Italy to be infected, unless it is in some specific areas, such as Bergamo, a severely affected area. Only large-scale serum testing studies can provide more reliable estimates.

In Zeng Guang's view, the usefulness of such models is that after deducing the corresponding number of deaths and infection rates, on the one hand, it promotes the government to introduce a more active public health policy; on the other hand, after the end of the epidemic prevention and control, the actual data The comparison is an assessment of the effectiveness of the policy.

But he said that the idea of ​​inferring whether to form "group immunity" through the model is wrong. The more rigorous way should be through solid epidemiological investigations and large-scale serum testing to obtain real data, that is, how big A proportion of the population is actually infected, how far is this number from the threshold for forming a "group immunity".

Is it just "the tip of the iceberg"?

Sunite Gupta, a professor of theoretical epidemiology at the Department of Zoology, Oxford University in the UK, clearly stated in an interview with the Financial Times that a large-scale serological antibody survey needs to be started immediately to verify the research results and assess the epidemic stage .

Jonathan Ball, a professor of molecular virology at the University of Nottingham, said that large-scale serum testing helps epidemiologists understand: the proportion of asymptomatic infections in the population, how many of these people have already developed immunity, and how many are infections What is the difference between asymptomatic infections and symptomatic infections?

On March 27, the World Health Organization also announced that it will launch a project called "Solidarity II" to conduct antibody testing in at least six countries around the world in order to understand the real data (including light Degree case). The WHO official responsible for coordinating the study explained: “This will help determine the prevalence and mortality of new coronary pneumonia in different age groups, and will help decision makers determine how long the blockade and quarantine should last.” Preliminary investigations The results may come out within a few months, and the research plan lasts a year or more.

These all help to test the most alarming hypothesis in the epidemic: are the cases we are seeing just the “tip of the iceberg” of all infected people? In the coming weeks and months, these questions will have a clearer answer.

On April 3, the US Food and Drug Administration (FDA) authorized an enterprise to produce rapid antibody detection reagents through emergency procedures for the first time. Antibody testing is different from the large-scale nucleic acid testing used in the epidemic. The latter can only catch infected people with "active viruses" in the body by sequencing the viral genes. The former can detect whether a person has been infected with the virus, even if he Has been restored. But antibody testing is not conducive to screening for epidemics in the early stage, because people can produce enough antibodies at least 10 to 14 days after being infected with the virus to achieve protective immunity.

In Colorado, United States, the well-known biomedical company United Biomedical has conducted a large-scale antibody test on 8,000 residents in a county.

According to the German magazine "Der Spiegel", researchers from the German National Laboratory Helmholtz Infection Research Center said on March 27 that in the next few weeks, hundreds of thousands of antibody tests will be conducted and may have been given to People who produce antibodies issue certificates of "immunization" so that they can no longer be restricted by the "blockade" policy and can travel.

The Johnson government of the United Kingdom announced on March 25 that it had purchased 3.5 million antibody detection reagents and would use them in isolation in the next few days. But medical consultants are more cautious about this. Unlike the statement that Minister of Health Matt Hancock will start the test "very quickly", they pointed out that the test will not be carried out very quickly. Before that, the effectiveness of the reagents needs to be evaluated. Chris Whitty, the UK ’s chief medical officer, warned that what is worse than the lack of detection is false detection. People diagnosed with "false negatives" will go out with ease and then be infected. But he also said that once the accuracy of these reagents is confirmed, they will be distributed to the community immediately. It is understood that the evaluation of the reagents is being carried out by the Gupta team at Oxford University, which released the aforementioned research.

Zeng Guang pointed out to China News Weekly that countries should decide whether to promote large-scale antibody testing at this stage according to their actual epidemic prevention situation. In China, the time for antibody testing is ripe. But organizing such epidemiological investigations requires a lot of manpower, material and financial resources. He suggested that national-level institutions organize such epidemiological investigations, rather than let the localities do their own work and understand only a small area.

Wang Chen, academician of the Chinese Academy of Engineering and dean of the Chinese Academy of Medical Sciences, disclosed on April 3 that the central government has made it clear that the epidemiological investigations of key areas are required to organize populations, mainly nucleic acids and serum antibodies. The so-called asymptomatic infection. To strictly and scientifically and economically design and sample surveys, it is not simply to find a few healthy people for examinations, or for all people.

Through this sampling, it is necessary to be able to find out the overall immune status of the population and the proportion of asymptomatic infections. Doing this now can reflect the current baseline level. Three months and six months later, it can reflect the immunity and disease prevalence of future groups.

"With this basis in our hands, we can formulate scientific prevention and control measures, and then we can take the initiative when the countries in the world are generally affected by the epidemic, and we will not fall into the passive." Wang Chen said.

Huang Yanzhong, a senior researcher in global health at the American Council on Foreign Relations and a professor at the School of Diplomacy and International Relations at West East University, said in an interview with China News Weekly that antibody testing in key areas can start with Wuhan and cover or conduct as much coverage as possible. The selection of large samples, after obtaining the corresponding real data, can also confirm each other with the previous nucleic acid test results, and communicate the authenticity of China's data to the outside world. "In this sense, testing has not only economic and social significance, but also diplomatic significance."

In fact, even though the fact that "the tip of the iceberg" has been confirmed by antibody testing, Huang Yanzhong believes that to achieve the so-called "group immunity" still needs to meet a premise: the virus will not mutate. The new crown is an RNA virus with a high mutation rate. Although it is not possible to predict whether it will mutate like influenza, the potential for mutation should be considered.

However, Jin Dongyan, a professor at the School of Biomedical Sciences of the University of Hong Kong, pointed out that the mutation rate of the new coronavirus is significantly lower than that of SARS, and the human body's immune response to the virus will not fade quickly. "At least 6 months, within a year will not be infected." He said.

A research report released by the COVID-19 (International Name of New Coronavirus) emergency team of the Imperial College of Technology in the United Kingdom also pointed out that according to the influenza research platform "Influenza Surveillance", antibodies have been produced for coronaviruses of the same genus as New Coronavirus. Of people cannot be infected again in the same quarter or the next quarter.

Zeng Guang also pointed out that once antibodies are formed in the body, whether it is short-term immunization or life-long immunization is not easy to say. Existing research on antibodies is not enough, and many questions about the new coronavirus have not been resolved. For example, how large a titer of antibody must be in the body to ensure resistance to the next coronavirus infection?

"Interleaved Group Immunization"

"This will completely change the entire game." Boris said after the British government announced that "soon" large-scale antibody testing will be conducted.

Sunite Gupta, a professor of theoretical epidemiology at the Department of Zoology at Oxford University, pointed out that if antibody testing confirms the model results, the UK currently adopts a series of restrictions including school closures, suspension of parties, and suspension of large-scale activities. End sooner than the British Ministry of Health had previously expected.

Behind the discussion of "group immunization", the original motivation came from the government.

When the concept was first proposed, Valence explained that since the vast majority of patients with new crowns are mild, when more mild patients are infected with the virus, the spread of the epidemic will be slowed down to prevent it from coming back next winter. The background of this speech was the day before Boris made it clear that the UK's epidemic prevention and control entered a "deferred" stage, by flattening the curve to delay the arrival of the peak, to prevent the rapid rise of medical demand in the short term to break the British National Medical Service System (NHS).

If you do n’t get stuck in a word game like “group immunization requires at least 60% of the British, that is, about 40 million people infected”, but carefully examine the essence of this strategy, you can find that in other European countries and the United States, regardless of Before the implementation of the "blockade" before March, the policies adopted are all variants of "group immunization".

Compared with the United Kingdom, Germany's approach is more "steady and steady", and more active detection measures were taken at the beginning of the outbreak, thanks to Germany's more developed medical system and a more adequate plan for such epidemics. However, even if there is a difference of 1 to 2 weeks, almost all countries have adopted "blockade" measures in the middle and late March. The United Kingdom has entered "containment" from "deferred", the US states have imposed curfews, and Germany has adopted "three steps" to intercept from , Protection to loss.

In the Imperial College of Technology model that led to the Johnson government ’s policy shift, the model ’s main researcher and the school ’s epidemiologist Neil Ferguson proposed that although “containment” is a more urgent measure in the UK than “delay”, Shut down schools, restaurants, entertainment venues, and adopt social isolation measures. Although it will slow the spread of the virus in the short term, once it is released, it may usher in a greater rebound, because "not formed in a sufficient number of people. Immune defense line ". In fact, whether in academic or political circles, there is no objection to his judgment.

Huang Yanzhong pointed out that this is based on the same understanding: the golden window period for "containing" the virus has been missed. All measures are aimed at slowing down the spread of the virus and at the same time reducing the harm caused by it, which includes harm to public health and the economy. That is, choose the least cost solution among the worst solutions.

Lu Mengji, a professor at the Institute of Virology at the Medical College of Essen University in Germany, pointed out that from the current situation, it is very difficult to completely remove the new coronavirus from the perspective of virology. The new coronavirus spreads strongly, and it will always spread in a certain range, and it can be completely blocked without relying on manpower. Before the birth of an effective vaccine, people were destined to live with the new coronavirus. For this time, a conservative estimate is 6 months, and Imperial College ’s model believes that it will take at least 18 months. In Lu Mengji's view, at least two years.

Mark Woolhouse, an epidemiology professor at the University of Edinburgh, made this clearer. He pointed out that there are currently only three ways out. The first one is a vaccine; the second one is enough people to establish a group immunity after infection; the third one is to change our behavior forever. The first option, you need to wait 12 to 18 months, the second type is roughly 2 years; the third type has no clear end point.

Lu Mengji said that the long-term coexistence of Germany and New Coronavirus is "relax, tighten, loosen, and tighten again". The spread of the virus and the increase in the number of cases will also be wavy, which has been in a controllable At the level, the epidemic cannot end until everyone has immunity. In this process, Germany is also using big data analysis to find where the key points of spread are, and perhaps a better entry point for preventing and curing the new coronavirus.

"Know where to investigate and tighten up, and where to relax. Through this wave of learning, we may have ran through the virus. The virus continues to spread, but it will not overwhelm our entire medical system. "In Lu Mengji's view, this is equivalent to the name of no group immunization, the practice of group immunization.

In Imperial College ’s model, the German idea of ​​“elasticity” has proved effective. Ferguson pointed out that this is a "more flexible strategy", and strict control measures are taken in the early stage of the outbreak, but an "exit" mechanism should be set up to relax the control when the patients diagnosed by the ICU are below a certain "threshold" When it exceeds the “threshold”, it triggers a new round of strict control, just like a “switch”.

He pointed out that this trigger mechanism is more robust than continuous control measures, and can also allow each region to adjust flexibly according to its own situation. For example, in the United States, it can be based on states. But he expects that in a year, at least two-thirds of the time to take strict control until the vaccine appears.

Sanjeev Sabhlok, a professor at the School of Economics at the University of Southern California in the United States, called this method "interlaced group immunization" in an interview with Science. He pointed out that the strategies currently adopted by Switzerland, Israel, Malta and many Southeast Asian countries are just variants of it. British chief consultant Madley and Australian epidemiologist Tony Blakely share the same view. The latter's famous statement is that the economic consequences of flattening the curve can also cause death.

Sabhlok believes that the longer the "blockade" lasts, the greater the marginal cost. In his view, while the "blockade" caused the government's fiscal revenue to drop sharply, it also had to send money to the poor. This double blow prevented the government from continuing to perform some non-epidemic responsibilities, and ultimately required taxpayers in the next few decades. Pay in the middle. In addition, the "blockade" has also exacerbated social inequality, and the rich will always find better shelter.

According to estimates by the World Economic Cooperation Organization (OECD), the "blockade" will reduce GDP per month by 2%, which is 22 trillion yuan in global economic losses. The International Monetary Fund (IMF) said the impact of the epidemic on the economy will exceed that of the 2008 financial crisis.

Sabhlok predicted that not long afterwards, when the economic situation of society further deteriorated, now these empty "save all lives as possible" statements will quickly give way to "let us do our best to save our country." "It's time to think about how to end the game." He said.

On March 10, Huang Yanzhong discovered during the US Congress hearing that many small businesses could not support it. Now, another month has passed. If the "blockade" continues, it will cause many social problems.

Therefore, at the April 4 epidemic briefing, although Trump warned Americans that “the situation is not optimistic” and said the death toll will peak in the next few days, he still “reopened the economy” again. He proposed that he is considering the establishment of another White House New Corona Virus Task Force, focusing on the economy and reopening the country. He said: "The original intention of this country is not closed. Think about it, we have to pay for people who do not work, how does this work?"

Earlier, Trump had disregarded domestic public opposition and hoped that the United States would reopen its economy before Easter. As the US epidemic data soared, it changed its name to "this is an ideal" and announced the extension of "social isolation" measures until April 30.

In the United Kingdom, on March 23, the "blockade policy" instruction was issued, and the Johnson administration emphasized that the feasibility of the policy will be reassessed every three weeks. By April 13th, it was exactly the end of the first round, so Medley immediately said that after the "group immunization", the prime minister will make a "significant decision."

So far, the British "blockade" policy has been carried out for two weeks, and France, Germany, the United States and other countries that have begun earlier have lasted for three weeks. Countries are thinking about a question; if at least the winter of 2020 is to be spent without vaccines, can society bear such long-term large-scale control?

Leaders of EU countries called for an "exit strategy" as soon as possible in a video conference on March 26.

Wang Chen pointed out that in the case of shortage of resources, some Western countries will sternly seek survival. "In this way, there may be a situation in the future. After the people in Europe and the United States have suffered a great loss, the immunity of the people will come up. It can open the country, and it is not afraid." He said.

Huang Yanzhong described it as "intentionally planting willows," "It's not about intentionally blooming, this is not a strategy they actively choose." He also said that if the European and American countries form a de facto "group immunity" in the future, China will be in a very dangerous situation Situation, the so-called "immune gap" is formed. He suggested that the vaccine should be developed as soon as possible; secondly, the strategy of "building a high wall" should be adopted to prevent foreign imports. Do not relax at all, otherwise everything China has done before will be abandoned.

Gao Benen, a professor at the School of Public Health at the University of Hong Kong and an honorary academician of the British School of Public Health, suggested to China News Weekly that China should carefully consider whether the blockade policy should be adopted again when the second wave of outbreaks comes.

"China News Weekly" No.13, 2020

Statement: The publication of the "China News Weekly" manuscript is subject to written authorization