End the COVID-19, or coexist with it? Five reasons may lead to the failure of herd immunity

In the long run, COVID-19 may become a local epidemic like influenza, and scientists are planning a new normal for the epidemic when herd immunity cannot be achieved. This article will explain some of the reasons behind this idea and its significance for the continued spread of COVID-19 for readers to think about and discuss.

By Christie Aschwanden

Compiled by Hong Junxian

Original title: "End the new crown, or coexist with the virus? Five reasons may lead to the failure of herd immunity, and the new crown may be the next flu"

The road to normalization of the epidemic: from "pandemic" to "endemic"

“How long will the coronavirus pandemic last?”

The national COVID-19 vaccination work is in full swing, and the global vaccination rate is also increasing rapidly. Everyone can't help but be full of hope: Is this epidemic coming to an end?

However, the academic community believes that the answer seems to be still full of uncertainty. Even if all countries are fully committed to vaccination, the threshold of completely conquering COVID-19 is still out of reach. The once popular and highly anticipated strategy of "herd immunity to end COVID-19" seems to have become unrealistic.

Figure 1: Schematic diagram of herd immunity strategy [1]. Herd immunity strategy refers to a strategy that hopes that enough people will gain immunity and the proportion of the immune population will reach a certain threshold (that is, the proportion of susceptible individuals in the group is low enough), thereby indirectly protecting the susceptible population and blocking the spread of the virus. Generally speaking, this threshold is 60% to 70% of the population has been immune. The main ways to gain immunity are ① artificial vaccination and ② natural infection by the virus.

Generally speaking, reaching the threshold of herd immunity mainly depends on artificial vaccination, and the vaccination rate must reach a certain level. The academic community once believed that once large-scale vaccination began, herd immunity could be achieved quickly and normal social order could be restored. However, as humans entered the second year of the "new crown era", this idea has also changed.

Youyang Gu is an independent data scientist. At the beginning of the epidemic, he personally built a death toll prediction model with extremely high accuracy, far exceeding the official prediction models of Imperial College London and the Institute for Health Metrics and Evaluation in the United States. [2] Previously, he named his epidemic prediction model "Path to Herd Immunity", but now he has renamed the model "Path to Normality". Youyang Gu believes that due to factors such as people's hesitation to get vaccinated, the emergence of virus mutants, and delayed vaccination of children, herd immunity seems to be difficult to achieve. This view is exactly the same as that of many epidemiologists. Lauren Ancel Meyers, executive director of the COVID-19 Modeling Organization at the University of Texas at Austin and a well-known epidemiologist, also believes: "We have given up the idea of ​​ending the pandemic with herd immunity."

The change in the academic community's attitude towards herd immunity reflects the complexity and challenges of the epidemic, but it does not mean that vaccination is unhelpful. Meyers said: "Vaccination means that the epidemic will gradually subside on its own. But as new mutant strains continue to emerge, people's resistance to viral infections may be weakened. We may still be fighting the new crown in a few months or even a year, and we must always be prepared to deal with future uncertainties."

In the long run, the new coronavirus may become an endemic like influenza, and scientists are also planning a new normal for the epidemic when herd immunity strategies cannot be achieved.

Figure 2 - Path to Normality website homepage [3].

It is unclear whether vaccines can stop virus transmission

The key to herd immunity is that even if there are sporadic cases of infection, the spread of the virus will be blocked in time because there are not enough susceptible hosts in the environment. Therefore, an important condition for achieving herd immunity is that people who have been vaccinated or infected with the virus will not be infected or spread the virus again.

However, while vaccines appear to be highly effective in preventing symptoms, their effectiveness in blocking secondary infections and viral transmission remains to be determined. As Georgetown University mathematical biologist Shweta Bansal puts it, “herd immunity only makes sense if the vaccine can block viral transmission.”[4] Taking the mRNA vaccines from Moderna and Pfizer-BioNTech as an example, “the clinical data from the vaccines are indeed very encouraging, but it would be more meaningful if we could determine to what extent they can block viral transmission.”

Samuel Scarpino, a scholar at Northeastern University in Massachusetts, said, "If we want to achieve herd immunity, the vaccine's ability to block virus transmission does not need to reach 100%. Even if it only reaches 70%, the effect will be amazing." He believes that the virus is still spreading, which makes it extremely difficult to break the chain of virus transmission.

Figure 3: In a survey of scholars published by Nature magazine, almost 90% of respondents believed that COVID-19 would become an endemic [5].

Endemic refers to an epidemic that persists in a specific region or population. The scale of infection tends to stabilize due to factors such as a certain proportion of the population developing immunity, such as malaria in some tropical regions. Pandemic refers to an epidemic that spreads widely around the world and affects a large proportion of the population, also known as a "pandemic." In March 2020, the World Health Organization declared that the new coronavirus pneumonia had become a "pandemic."

Vaccine promotion and distribution are difficult to achieve balance

The distribution and speed of vaccination are affected by many factors, and there are huge differences in the rate of vaccination promotion between countries and even within the same country. Matt Ferrari, an epidemiologist at Pennsylvania State University, said that it might be theoretically possible to eliminate the new crown pandemic through a "perfectly coordinated global campaign", but in reality it is unlikely that humans will achieve this goal on a global scale.

Israel began vaccinating its citizens in December last year and is leading the world in vaccine promotion, but the effect of herd immunity remains uncertain. Dvir Aran, a biostatistician at the Israel Institute of Technology, said that in the early days of vaccine promotion, more than 1% of the country's population was vaccinated every day; as of mid-March, about 50% of the Israeli population had received all doses of the vaccine. He believes that the main problem at present is that young people are reluctant to get vaccinated, and the local government has to start using activities such as free pizza and beer to attract young people. In sharp contrast to Israel, the proportion of people vaccinated in its neighboring countries Lebanon, Syria, Jordan and Egypt is less than 1%.

In the United States, the rate of vaccine promotion varies from place to place. In some states such as Georgia and Utah, the proportion of people who have received a full dose (completed two injections) of the vaccine is less than 10%, while in places such as Alaska and New Mexico, the population that has received a full dose of the vaccine has exceeded 16%.

In most countries, vaccines are allocated by age. Generally, the elderly are given priority because they are at the highest risk. However, it remains to be seen when and whether vaccines will be available for children. Pfizer and Moderna have already begun recruiting adolescents to participate in vaccine clinical trials (Pfizer just announced clinical results for 12-16 year olds last week[6]); vaccines from Oxford-AstraZeneca and China's Sinovac Biotech are also being tested in groups such as three-year-olds. Bansal believes that if children cannot be vaccinated, more adults will need to be vaccinated to achieve herd immunity.

Currently, the Pfizer vaccine is available for people aged 16 and above, while most other vaccines are only available for people aged 18 and above.[7] Taking the United States as an example, according to the 2010 census data, the proportion of people under the age of 18 is 24%. If most people under the age of 18 cannot be vaccinated, then 100% of the population over the age of 18 must be vaccinated to achieve the 76% immunity requirement for the overall population.

The geographic structure of herd immunity is equally important, including the "immune fortresses" formed around communities. Previously, due to the public's clustering behavior and poor policy control, communities across the United States have experienced COVID-19 epidemics. Historical vaccination work has shown that the number of vaccinations will show a geographical community clustering effect. For example, local residents' resistance to measles vaccines has led to a small-scale measles resurgence. Even in a country with a high vaccination rate like Israel, if neighboring countries cannot achieve high levels of immunity and the population can still circulate, new outbreaks may still occur.

"Geographic clustering makes the path to herd immunity more tortuous," Bansal said, using a vivid analogy. "It's like playing whack-a-mole."

Figure 4: World vaccination rates. Israel leads the world in vaccine rollout, but the effectiveness of herd immunity remains uncertain. Source: Our World In Data.

Mutants disrupt herd immunity balance

At the same time that vaccine promotion and distribution face huge obstacles, the new coronavirus is also constantly producing new mutant strains, some of which may be more transmissible or more able to escape the protection of vaccines. As Sara Del Valle, a computational epidemiologist at Los Alamos National Laboratory in New Mexico, said, "We are racing against viral mutations. The longer the virus spreads, the more likely it is that mutant strains will appear and spread."

In terms of mutant strains, the development of the epidemic in Brazil seems to be a warning to the world. A study published in the journal Science by Ester Sabino's team at the University of São Paulo [8] showed that the infection rate of the new coronavirus in Manaus, Brazil, was over 60% in June last year, enough to reach the threshold of herd immunity; from May to October, the number of new coronavirus cases in the area continued to decline, which may be attributed to the herd immunity effect. However, due to the emergence of the new P.1 mutant strain, the number of local infections surged again in January. (For details, see "A Big Review of New Coronavirus Mutants: Mutations Will Continue, Where Will Humanity Go? | 117 Three People")

"100% of the cases in Manaus in January were caused by the P.1 mutant, which suggests that previous infections are likely unable to protect against new mutants," wrote Ester Sabino. Scarpino suspects that the previous estimate of 60% infection in Manaus may be too high, but even if 60% of the population is immune, there will still be new outbreaks.

As the proportion of people who are immune gradually increases, new problems may also emerge. Ferrari believes that a higher proportion of people who are immune will exert evolutionary selection pressure on the virus, thereby promoting the generation of mutant strains, which can then infect the immune population. Therefore, the faster and more thorough the vaccination, the better, in order to reduce the generation of mutant strains.

“Uneven vaccination puts people in an intermediate state, where on the one hand they have higher immune protection, but on the other hand they may also have an increased risk of infection,” Ferrari said. “Because vaccines will almost inevitably create new evolutionary pressures and promote the emergence of mutant strains, we need to establish the corresponding infrastructure and operational procedures to continuously monitor the development of mutant strains.”

Immune protection may not last

As mentioned above, the mathematical model of herd immunity mainly considers two sources of individual immunity, namely vaccination and natural infection. Bansal believes that people who have been infected with the new coronavirus seem to have a certain degree of immunity, but the specific duration of this immune protection remains a mystery. Combined with the understanding of other coronaviruses and some preliminary evidence from the new coronavirus research, the immunity brought by viral infection seems to weaken over time.

"We still lack hard data on the decline of immunity to COVID-19, but what is certain is that the immune protection obtained by the human body after infection is neither zero nor 100%." ​​Bansal said that when calculating the threshold of herd immunity, the mathematical model cannot accurately include every infected individual, and it is also necessary to consider the fact that vaccine protection is not 100% effective. If the immune protection after infection can only last for a few months, then the vaccination period is more urgent - basically, the vaccination period is equal to the immune protection period. At present, the follow-up results of the third phase of the Pfizer vaccine clinical trial show that the effectiveness of the second dose of the vaccine remains at 91% six months after vaccination [9]. Many experts speculate that the duration of immune protection will exceed 1 year.

It is important to understand how long the vaccine provides protection and whether booster vaccinations are needed over time. Therefore, COVID-19 may well become the next flu.

Vaccinations can affect social behavior

Aran believes that at the current vaccination rate, Israel is approaching the theoretical herd immunity threshold. However, as more people are vaccinated, their social and group activities will increase accordingly, and the risk of virus exposure will change accordingly, thus changing the balance of herd immunity.

Vaccines do not make people invulnerable. For example, if a person contacts at most one person a day, and he is vaccinated with a vaccine that protects him 90%, but after vaccination he contacts 10 people a day, then the overall risk of infection will return to the original level.

"The most challenging aspect of modeling COVID-19 may be the sociological factors," Meyers said. So far, the models have not taken into account how people behave. In this unprecedented era, people behave in unprecedented ways. Meyers and others are trying to adjust statistical models to accommodate changes in behavioral patterns such as wearing masks and social isolation.

Del Valle also said that non-drug interventions will still play an important role in epidemic control. The key to breaking the transmission route is to limit social contact and continue to take protection (such as wearing masks), which can also effectively reduce the spread of mutant strains.

However, it is quite difficult to prevent people from returning to their pre-epidemic behavior patterns. A large part of the population in Texas and some other states in the United States has not yet been vaccinated, but local governments have already lifted the mask order. Many scholars have expressed "very frustrated" about this, because continuing to take measures such as restricting gatherings will undoubtedly play a huge role in ending the epidemic. Scarpino said that herd immunity may not make us "absolutely safe", but it can make us "safer."

Figure 5: Protesters in California, USA, call for an end to social restrictions imposed due to the COVID-19 pandemic. [10]

To understand the synergy of social behavior restrictions and herd immunity protection in controlling the epidemic, the low level of influenza this year is the best example. Scarpino said that the influenza virus may not be inferior to the new crown in its ability to spread, but there has been no widespread influenza epidemic this year, which can almost certainly be attributed to the synergy of herd immunity protection and social restrictions. Generally speaking, about 30% of the population has been infected with influenza in previous years and has become immune, and another 30% of the population will be vaccinated, bringing the herd immunity level to about 60%. Coupled with measures such as wearing masks and restricting social interaction, it is difficult for influenza to become popular. This strongly illustrates that social behavior will greatly change the development of the epidemic. If people want to lift the ban and open up social activities, a higher proportion of the population will need to be immunized accordingly.

The speed of development of the new coronavirus vaccine is truly amazing, but it seems that vaccines and herd immunity strategies alone can no longer completely block the spread of the virus. We may need to consider more realistic possibilities.

But fortunately, the situation is not as dire as it sounds. Because even if herd immunity is not achieved and the desire to end the virus cannot be realized, vaccinating high-risk groups will greatly reduce the number of hospitalizations and deaths caused by the new coronavirus. This means that even if the new coronavirus will not disappear soon, its harmfulness is likely to be greatly weakened.

As Stefan Flasche, a vaccine epidemiologist at the London School of Hygiene & Tropical Medicine, puts it: “We can also get life back to normal by reducing the rates of severe illness and mortality.”

Source: Nature 591, 520-522 (2021) doi: https://doi.org/10.1038/d41586-021-00728-2

References

[1] Randolph HE, Barreiro LB. Herd Immunity: Understanding COVID-19. Immunity. 2020;52(5):737-741. doi:10.1016/j.immuni.2020.04.012

[2] https://www.bloomberg.com/news/articles/2021-02-19/covid-pandemic-how-youyang-gu-used-ai-and-data-to-make-most-accurate-prediction

[3] Path-to-herd-immunity. https://covid19-projections.com/path-to-herd-immunity/

[4] Can COVID vaccines stop transmission? Scientists race to find answers. https://www.nature.com/articles/d41586-021-00450-z

[5] The coronavirus is here to stay — here's what that means. https://www.nature.com/articles/d41586-021-00396-2

[6] https://www.pfizer.com/news/press-release/press-release-detail/pfizer-biontech-announce-positive-topline-results-pivotal

[7] Product Info by US Vaccine. CDC.

https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/index.html

https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/index.html

[8] Buss LF, Prete CA Jr, Abrahim CMM, et al. Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic. Science. 2021;371(6526):288-292. doi:10.1126/science.abe9728

[9] Pfizer and BioNTech Confirm High Efficacy and No Serious Safety Concerns Through Up to Six Months Following Second Dose in Updated Topline Analysis of Landmark COVID-19 Vaccine Study | pfpfizeruscom

[10] COVID-vaccine results are on the way — and scientists' concerns are growing. https://www.nature.com/articles/d41586-020-02706-6