How should human socity deal with COVID-19 Delta mutant strain?

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How should human socity deal with COVID-19 Delta mutant strain?

How should human socity deal with COVID-19 Delta mutant strain? What is the COVID-19 Delta mutant strain and how should we deal with it?

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First published an article on the analysis of delta mutant strains of intellectuals. Many people have asked about this mutant recently. In fact, you don’t have to worry too much about whether the vaccine is still effective. Instead, we should be concerned about whether we can further increase the vaccination rate, curb virus amplification, and prevent the next mutation from appearing.

Preface

Since the outbreak of the COVID-19 epidemic in India in April, a mutant strain named B.1.617 has quickly become the focus of the world with its amazing spreading speed.

Among them, a branch of B.1.617, B.1.617.2, the Delta mutant strain, is even more fierce. It has become the most important virus strain in the new cases in the UK, forcing the UK to postpone the original full opening time. It is very likely that it will soon become the most common virus strain in the United States.

What is so special about the Delta mutant strain, how threatening is it, and how should we deal with it?

01. Past and present of Delta mutant strain

The Delta mutant strain came into our sight with the outbreak of the epidemic in India a few months ago. At that time, the B.1.617 mutant strain, which was called the double mutant strain by the media, was considered by some to be the culprit of the sudden deterioration of the epidemic in India. Many people have also got the impression that the B.1.617 mutant strain, including the Delta mutant strain, is a new mutant strain that originated in India this year.

But these statements are flawed or even incorrect.

First of all, the genome information of the B.1.617 mutant strain was uploaded to the global COVID-19 genome sequence database as early as early October 2020. In other words, B.1.617 appeared at least in October last year. The time when B.1.617 was detected in the United Kingdom, the United States and other countries was also far earlier than the time when the B.1.617 strain or the Delta mutant strain under it entered the public eye. For example, on February 22 this year in the United Kingdom and the United States on February 23 this year, the genomes of the earliest B.1.617 strain were uploaded respectively [1]. In fact, it is still unclear where the B.1.617 strain first appeared.

Secondly, “double mutation” is not an accurate description of the B.1.617 strain or the Delta mutant strain [1]. B.1.617 was originally called a double mutant because it was discovered that there were two mutations L452R and E484Q on its spike protein, which also appeared in the other two mutants.

But these two mutations are not the only mutations on the B.1.617 strain. For example, there are as many as 13 mutations that cause amino acid changes.

On the branch of B.1.617, there are three mutant strains or subbranches based on the difference of specific mutations-B.1.617.1 (Kappa mutant strain), B.1.617.2 (namely Delta mutant strain) and B.1.617.1 (the Delta mutant strain). 1.617.3.

The three subbranches of B.1.617, including Delta, all have L452R mutations (this mutation also exists in the Epsilon mutant strain B.1.427/429 that was first discovered in the United States), and D614G mutations (many highly infectious mutant strains) All carry this mutation, such as Alpha, Beta, Gamma mutant strains, etc.), P681R mutation.

Unlike the other two subbranches, the Delta mutant does not have E484Q, but has a T478K mutation.

It should be noted that it is normal for the virus to produce mutations during the replication process, and it is unavoidable. But not all mutations will have a substantial impact. What we need to care about is whether the mutations cause changes in the functionality of the virus, such as increased infectivity, increased pathogenicity, or reduced effectiveness of drugs or vaccines.

As far as the Delta mutant strain or the B.1.617 strain is concerned, the D614G and P681R mutations may increase the ability of the virus’s spike protein to bind to the human ACE2 protein, leading to an increase in virus infectivity. The L452R and E484Q mutations may not only increase the binding force to the ACE2 protein (increase infectivity), but also cause a certain degree of immune escape-specifically, the effectiveness of some monoclonal antibody drugs currently developed against the original virus strains has decreased. , The immune protection obtained by natural infection with the original virus decreases, and even the effectiveness of the vaccine may decrease.

Because of these interesting mutations, the B.1.617 branch showed a high proportion of cases in the Indian epidemic and immediately aroused the world’s vigilance.

02. The most infectious mutant strain so far has increased pathogenicity

Theoretically, having mutations that lead to greater contagion does not necessarily mean that there is a stronger ability to spread in the real world. In addition to studying the effects of these mutations in the laboratory, it is more important to monitor the “performance” of mutant strains in the real world.

Unfortunately, the “performance” of the B.1.617 strain, especially the Delta mutant strain, in the real world, especially its stronger spreading power, has not only been verified but even far surpassed the threat we had previously speculated based on the mutant amino acid. .

In fact, in the large outbreak of the epidemic in India, there is a certain controversy about how much responsibility the B.1.617 strain should be responsible for. India is not a country that does a good job of monitoring viral genomes. At the peak of the epidemic, there was no clear data indicating that B.1.617 was the most important virus strain. At the beginning of May, the virus genome surveillance in one state in India indicated that B.1.617 was the most local, but the surveillance in another state pointed to Alpha mutant strains.

This contradictory result reflects the uneven sampling of virus genetic monitoring in India. For example, sampling is concentrated in large medical centers in large cities, which makes it impossible for us to understand the true prevalence of different mutant strains. It can only be said that the B.1.617 strain should account for a large proportion of the previous epidemic in India, but it is difficult to say that it is the absolute dominant factor. But then, the Delta mutant strain spread at an alarming rate, and with its own efforts, the epidemic in many countries appeared to be repeated or even new peaks.

On May 7, the British Public Health Department monitored the change in the number of cases and believed that the transmission capacity of the Delta mutant strain might be at least as good as that of the Alpha mutant strain, and immediately upgraded the mutant strain from a “variant under investigation” (variant under investigation) to “Variant of concern” [2]. On May 11, the World Health Organization also classified the Delta mutant as a “worrying mutant.”

Delta’s communication ability still surpasses the early predictions of scientists. Since April in the United Kingdom, the Delta mutant strain has accounted for an increasing proportion of new infections. From May 5th to 12th, within seven days, the proportion of Delta mutant strains in the sequencing monitoring of new cases in the UK has exceeded 20%, with a total of more than 2,000 cases; from June 2nd to 9th, the proportion of Delta mutant strains has been Reached 90% of the new cases, an increase of more than 30,000 cases in seven days. The Delta mutant strain completely replaced the Alpha mutant strain and became the local dominant virus strain [2].

Based on this amazing growth rate, scientists currently believe that the transmission capacity of the Delta mutant strain is likely to be 1.5 times that of the Alpha mutant strain, and the transmission capacity of the latter itself is 1.5 times that of the original COVID-19 virus strain. The United Kingdom also had to postpone the full opening date by one month due to repeated outbreaks caused by the Delta mutant strain.

How should human socity deal with COVID-19 Delta mutant strain?

The Delta mutant strain spread at an alarming rate, becoming a “worrying mutant strain” | pixabay.com

Delta mutant strains are competing for the status of mainstream virus strains, not only in the UK, but also in many countries. From the end of May to the beginning of June, the proportion of Delta mutant strains in the United States, Germany, the Netherlands and other places was still between 2-10%, but then increased at a rate of 2-3 times per week. The latest virus genome monitoring in the United States shows that the proportion of Delta mutant cases accounted for more than 20% in late June, and it will almost certainly repeat the scene where the British Delta replaces the Alpha mutant [3].

In addition to the ability to spread, another aspect of the new coronavirus mutants we are concerned about is the pathogenicity, especially whether there is a change in the risk of causing severe illness. In this regard, some preliminary observational research results are worrying. On June 14, “The Lancet” officially published a study based on Scottish public health surveillance data and found that compared with the Alpha mutant, the risk of hospitalization for people infected with the Delta mutant has doubled [4].

03. Fortunately, The vaccine is still effective, but needs to be fully vaccinated

Faster transmission speed, higher risk of severe illness, all of these make Delta’s threat to come and go. But among the many worrisome information, we still have a very good news, and also an extremely important discovery, that is, for the Delta mutant strain, many COVID-19 vaccines still have a very good protective effect.

For newly emerged mutant strains, there are two research methods that can help us explore the effectiveness of existing vaccines, namely serum neutralization experiments and vaccine effectiveness tracking studies.

The first is to do experiments in the laboratory with the sera of vaccinators to see if these sera containing neutralizing antibodies due to the vaccine can continue to neutralize the mutant virus. If the ability of the vaccinator’s serum to neutralize the mutant virus drops significantly, or even loses the ability to neutralize, then we have to worry about whether the effectiveness of the vaccine will decrease or even fail.

On June 11, “Cell” magazine published the results of such a study [5]. Scientists from the United Kingdom found that after two injections of Pfizer/BioNTech mRNA vaccine and AstraZeneca/Oxford University adenovirus vaccine volunteer serum, the ability to neutralize the Delta mutant strain was significantly lower than that of the original virus strain. Vaccines dropped by 2.5 times and 4.3 times, respectively. However, it should be noted that although the neutralization ability has decreased, the serum of most of the fully vaccinated patients can still neutralize the Delta virus.

At the same time, the researchers also used the sera of 20 volunteers who had only received one shot of Pfizer/BioNTech vaccine to test the neutralizing ability of these “half-vaccinated” sera against different new coronavirus strains. It was found that after 4 weeks of vaccination, the sera of 16 vaccinators could neutralize the original virus strain; after 10 weeks, the sera of 9 vaccinators could neutralize the original virus strain. But for the Delta mutant strain, only 4 serums in the 4-week sample can be neutralized, and after 10 weeks, none of the samples have reached the “qualified line” set by the experiment.

This virus neutralization experiment shows that the Delta mutant strain is likely to have a certain immune escape for current vaccines. Although the protective effect of full vaccination is still good, the effect of “half vaccination” needs to be worried.

However, this type of neutralization experiment is still only to deduce the effectiveness of the vaccine through in vitro experiments. The actual protective effect of the vaccine in the human body does not only depend on the existing neutralizing antibodies in the serum, but also depends on the ability to be mobilized to produce antibodies in large quantities at any time. Memory B cells and killer T cells that can directly destroy virus-infected cells and prevent the virus from expanding in the body.

So the more important thing is whether we have observed a decline in vaccine effectiveness in the real world. For example, compared with unvaccinated people, what is the risk of the vaccinated person being infected with the Delta mutant? Whether there is a change in the risk of infection compared with other virus strains.

After continuously tracking the sequencing results and vaccination status of the local COVID-19 infection, the British public health department also recently announced the effectiveness of the vaccine against the Delta mutant strain [6]. This study adopted a method similar to tracking the effectiveness of influenza vaccines, by analyzing how many cases of nucleic acid tests were positive and how many cases were negative among people who came to the hospital for testing after the appearance of COVID-19 symptoms, and then based on the tester’s vaccination status , Virus genotyping results, calculate the effectiveness of the vaccine for different mutant strains.

The population sampled in the study spans from early April to mid-May. During this time span, the two most common virus strains in the UK are the Alpha mutant strain and the Delta mutant strain, and the most commonly used vaccines in the area are Pfizer/BioNTech vaccine and A Sleek/Oxford University Vaccine.

According to previous studies, although the Alpha mutant strain has strong transmission ability, it has no immune escape phenomenon. That is, the COVID-19 vaccine developed against the original virus strain does not have the problem of reduced effectiveness for this mutant strain. In the above study, the population who received two doses of Pfizer/BioNTech vaccine and AstraZeneca/Oxford University vaccine were 93.4% and 66.1% effective against Alpha mutant strains, and 87.9% against Delta mutant strains. % And 59.8%.

This result shows that in the case of complete vaccination, the vaccine is still highly effective against the Delta mutant strain.

For people who received only one shot of the vaccine, according to the calculation results of the study, the above two vaccines are still 51.1% effective against Alpha mutant strains, but for Delta mutant strains, the effective rate is only 33.5%, which is a significant drop.

Integrating the serum neutralization experiment and tracking the effectiveness of the vaccine, it is not difficult to find that the vaccine is still highly effective against the Delta mutant strain, but it is extremely important to complete all the vaccination. In the case of incomplete vaccination, the protection of the vaccinators may be substantial. decline.

04. How to treat the endless COVID-19 mutations

The Delta mutant strain is currently spreading in many countries. How will it affect the prevention and control of the epidemic?

First of all, with its stronger spreading power, Delta is very likely to replace Alpha and become the dominant virus strain worldwide. It should be noted that the relationship between virus strains is not one and the other. Delta’s process of surpassing other mutant strains is likely to bring an increase in new cases. This has resulted in some countries where the epidemic situation has improved, and there may be relapses; other countries with severe epidemics themselves may face the pressure of new peaks of the epidemic [3].

Second, the Delta mutant strain may further increase the inequality of the epidemic. Worldwide, the distribution of vaccines is extremely uneven. For those who have been fully vaccinated, the threat of Delta is relatively small, but for those who have not been vaccinated or have not completed all the vaccinations, they will face great risks. In this context, the Delta mutant strain is likely to cause a very extreme “polarization”-places with low vaccination rates will face the risk of rapid deterioration of the epidemic, while places with high vaccination rates are likely to only encounter small scales. The repetitions can even be passed through safely.

Facing the menacing Delta, how should we deal with it?

There is no doubt that through effective vaccination, building an immune barrier is still the most important countermeasure. According to a British study [5], for the fully vaccinated population, Delta has almost no immune escape. So now we don’t have to worry about whether the vaccine is still effective, but whether our vaccination rate is high enough. At the same time, in the face of Delta, the “semi-complete” vaccination protection rate is obviously not enough, so try to let more people complete the full vaccination of the COVID-19 vaccine. In terms of vaccination rate, we can no longer focus on the “at least one shot” vaccination rate, but should focus on the “complete” vaccination rate.

In addition, not everyone can be vaccinated. For example, most children cannot be vaccinated with existing vaccines, and the effectiveness of vaccines for some special populations (such as those with immunosuppression) will be insufficient. We must pay more attention to the infection risk of these special populations, and find ways to formulate specific countermeasures, such as studying whether immunosuppressed populations can be vaccinated with enhanced injections to improve the protective effect of vaccines.

How should human socity deal with COVID-19 Delta mutant strain?
Building an immune barrier through effective vaccination is the most important measure to deal with Delta mutant strains | pixabay.com

The Delta mutant strain is not the first highly transmissible COVID-19 mutation we have faced. Since the epidemic is still serious worldwide, it is highly likely that it will not be the last mutant strain that poses a threat.

From the Alpha mutant strain at the end of 2020 to the Delta mutant strain today, in fact, we can also summarize many principles that are generally applicable to mutant strains.

First of all, the monitoring of virus mutations is very important. Only by continuously sampling infected cases and doing genome sequencing can we understand what mutations have occurred in the virus and which mutant viruses are on the rise.

Secondly, as multiple different vaccines are put into practical use on a large scale, we must always pay attention to whether each vaccine is effective against newly emerging mutant strains. Each vaccine is different, and it cannot be simply deduced from the performance of one vaccine against mutant strains to other vaccines. Only through timely follow-up of new mutations, serum neutralization experiments of different vaccines, and tracking of changes in vaccine effectiveness in the real world, can it be confirmed whether the vaccine is still effective. This is also related to whether we have to make adjustments to the vaccination strategy.

Furthermore, to achieve the above two points, international scientific cooperation has become particularly important, and may even become a prerequisite. We cannot predict where the next threatening mutation of the COVID-19 will occur. Due to the difference in the number of infected cases, not all countries can do research on the effectiveness of a vaccine against a certain mutant strain. Especially in countries where the epidemic is well controlled, such as China, it is difficult to study the effectiveness of the vaccine against the Delta mutant strain in China. All of this means that the exchange of “have or not” between different countries, the sharing of medical information and scientific research progress, will directly determine the speed and effect of the world’s decision-making on the COVID-19 mutant strain.

Finally, we must also see that due to scientific laws and some accidental factors, although the constantly emerging COVID-19 mutant strains are a threat, they have not fundamentally shaken our ability to control and eliminate the epidemic.

From a scientific perspective, COVID-19 is not a virus that mutates very quickly, and because it infects human cells completely depends on the spike protein, it also limits its mutation potential. This is also confirmed by the fact that multiple mutant strains originating from different regions (such as the Beta strain found in South Africa and the Gamma strain found in Brazil) share some mutation sites. Therefore, the COVID-19 mutation has a serious immune escape, and it is unlikely that the existing vaccine will be completely ineffective. In particular, more and more studies now show that there are not many neutralizing antibodies needed to protect severe illness, which means that even if there are immune escape mutations, the risk of vaccinators will be mainly mild or even asymptomatic infections. The risk of severe illness will be lower.

In addition, perhaps due to some accidental factors, it is precisely the virus strains whose immune escape is not serious that currently dominate. It is known that the most severe immune escape among the known mutant strains and the obvious decline in the effectiveness of multiple vaccines is the Beta mutant strain discovered at the end of 2020. However, this mutant strain has always been unable to compete with the Alpha mutant strain in the world. Now, due to the sudden emergence of the Delta mutant strain, it is unlikely to have a major spread. Therefore, although the emergence of one by one mutant strains is worrying, but in this process, the virus strains with the most severe immune escape are suppressed by other virus strains, which can be considered a blessing.

Of course, we cannot rely on this fluke forever, after all, no one knows the direction of the next mutation of COVID-19. But one thing is clear. No matter what kind of mutation, it must be caused by the continuous replication and expansion of the virus. The only way to prevent the next mutation is to reduce the spread of the virus through various epidemic prevention methods including effective vaccines. Opportunity to copy

(source:internet, reference only)

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