Israel: COVID-19 vaccine is really not as strong as natural infection?

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Israel: COVID-19 vaccine is really not as strong as natural infection?

Background:

A recent vaccine effectiveness study from Israel (Citation 1) caused a lot of discussion. Unlike most previous studies focusing on the effectiveness of vaccines, this study compares the effectiveness of the Delta mutant strain after vaccination and natural infection.

In the eyes of many people, this has become the PK between vaccines and natural infections in terms of immune protection. According to the results of the study, the protective effect of natural infection seems to kill the vaccine whether it is against infection or severe illness: the risk of breakthrough infection after vaccination is 13 times higher than that of the recovered patients, and the hospitalized group also has more vaccines than the rehabilitation group.

As a result of this research, there have also been many sighs on the Internet that “it is better to be infected naturally.” Regarding this, I think we still need to look at the problem comprehensively, which is comprehensive in several aspects:

First, the effect of vaccines and natural infections must be considered comprehensively. The protective effect is on the one hand, and the side effects should not be forgotten.

The second is to look at the research itself comprehensively, to see whether the research itself is sufficient, and whether there are other similar studies that can support it.

1. See the full effect of natural infection

We often say that there are two aspects to evaluating a vaccine, one is effectiveness and the other is safety. The safety of our current COVID-19 vaccine is so good that there are two phenomena when we discuss the safety of the vaccine.

One is a matter of course, that is, there is nothing to talk about about safety. It is safe. No matter how safe it is, it can only be normal saline. It is more effective than it is. Another phenomenon is that there are bones in the egg. The safety is too good, and there is nothing to do. For example, the XX vaccine will face paralysis, thrombosis, myocarditis and so on. When talking about this, many people forget the rarity of these adverse reactions. For example, thrombotic TTS, myocarditis, or pericarditis, which is accompanied by a decrease in platelets, have a probability of one in a million. Moreover, some of the rare adverse reactions discovered now are not serious. For example, most of the myocarditis and pericarditis of the mRNA vaccine are relatively mild and can be cured quickly.

But does the COVID-19 vaccine have such good safety, does it mean that the COVID-19 infection also has such good safety? Yes, since vaccines and infections come to PK, then we can’t just ignore the effectiveness of PK and ignore the safety.

In this regard, another Israeli research group just published an article comparing Pfizer/BioNTech vaccination with the adverse reactions after the COVID-19 infection in the New England Journal of Medicine. What is the result? All kinds of serious adverse reactions are basically the COVID-19 infection with an absolute high rate of victory.

Myocarditis has the highest increase in risk relative to the general population after vaccination, with an increase of 2.7 cases per 100,000 people. It is also myocarditis. What is the increased risk after the COVID-19 infection? An increase of 11 cases per 100,000 people. Of course, the COVID-19 infection also greatly increases the risk of arrhythmia, various blood clots, thrombocytopenia, and intracranial hemorrhage.

Israel: COVID-19 vaccine is really not as strong as natural infection?

Attached picture: Comparison of adverse reaction risks between Pfizer/BioNTech vaccine (blue) and COVID-19 infection (yellow) (from Citation 2)

What is the most common adverse reaction caused by vaccination? Lymph node enlargement, this is because the lymph node is the center of the immune response. As a local vaccine, it may naturally cause the lymph node (under the armpit) closest to the injection site to induce the immune response to cause swelling. But this is temporary and not serious. In contrast, there are 125 cases of acute kidney injury per 100,000 people with COVID-19 infections, 166 cases of arrhythmia, and 62 cases of pulmonary embolism, none of which is a joke.

When discussing the protective effect of natural infection with COVID-19, we must not forget the safety problem of natural infection, or the characteristics of insecurity.

In addition, it is better to say that natural infection is better. In most cases, there are survivors’ deviations. When someone tells you that I have recovered nothing and that the protective effect is better than that of your vaccine, you have to think about it. He can tell you that today. Maybe the infection is really good for him, but those People who are not so good after infection may have no chance to talk to you. For example, the millions of people in the world who have unfortunately passed away due to infection with COVID-19, can you ask how these people’s immune protection is?

Therefore, there is still uncertainty about the consequences of natural infections. You can’t predict whether you will get an “immune” card after infection or GG directly. If you want to treat natural infections as medicines, who is better than vaccines, don’t forget that as medicines, we need the safety and stability.

2. Study and research need to be comprehensive

Now COVID-19 is the hottest research topic in the world, and a lot of research is released every day. When drawing on the conclusions of a study, we also need to do comprehensive dialectical thinking.

The first level of this kind of thinking is to study and judge a study itself. People cannot say that everything is accepted. You have to consider what method the study used, what kind of data was obtained, and whether there are any flaws in it.

The Israeli study comparing natural infection and vaccination is a real-world study. For this type of study, we have to consider whether there are various interference factors, such as whether the behavior of vaccinators and those who have recovered from natural infections is essential. The difference, which ultimately leads to a different risk of infection? There is also the issue of the actual amount of data. For example, although the Israeli study is based on a population of nearly 700,000, in order to ensure that the various “features” of the research subjects are similar, the number of people who can finally be matched is only tens of thousands according to different standards. Group up. There are hundreds of infections in it, which is still sufficient, but when it is severe, there are only a few cases, and it is difficult to explain the problem.

Another aspect is that we have to consider whether a certain study has other studies to support it. For example, are there any similar studies before, and what are the results? Is there any mechanism behind this research conclusion? Is it reasonable?

Israel is not the only research involved in the protection of the natural infection of COVID-19. A recent study in the United Kingdom tracking the effectiveness of Pfizer/BioNTech and AstraZeneca vaccines against Delta also compared with natural infections (Citation 3). In this study, the effectiveness of the Pfizer/BioNTech vaccine was higher than that of the AstraZeneca vaccine at the beginning, but within three to four months, the effectiveness declined faster. After four or five months, the two vaccines were almost the same. . But at all time periods, the effectiveness of the two vaccines was not inferior to the protection brought by natural infections.

The British study also involved a large number of people, and it was compared with a control group who had not been vaccinated and had not been infected with COVID-19. Therefore, we should not accept all the results of the Israeli study, but take other studies into consideration.

The Israeli research is aimed at Delta. Before the emergence of a large number of mutant strains, even before the vaccine is used, there are studies on the protective effect of natural infections. Danish researchers have additionally analyzed the immune protection of 4 million people in the country during the first and second waves of the COVID-19 epidemic in 2020 (Citation 4). In that study, the effectiveness of natural infections to prevent secondary infections reached about 80%. However, the protective effect among the elderly over 65 years old dropped to 47.1%.

There is another study that should not be overlooked when discussing natural infections and vaccine effectiveness, and that is the clinical trial of Novavax vaccine in South Africa (Citation 5). Prospective, randomized double-blind clinical trials will eliminate various biases and interference factors better than real-world studies. The Novavax clinical trial coincides with the second wave of outbreaks caused by the Beta mutant strain in South Africa. In the placebo group, whether there has been a COVID-19 infection in the past has no protective effect on the Beta strain, but the vaccine group has significantly reduced the risk of COVID-19 disease.

Israel: COVID-19 vaccine is really not as strong as natural infection?

Figure 2: Natural infection has no obvious protective effect on the beta strain (lower left panel C), and the vaccine still has a protective effect (upper left panel A). Source: Citation 5.

Based on so many studies with different conclusions, it is better to be cautious to learn from this Israeli study. We can’t blow up natural infections just because of one study.

3. How to treat the effect of natural infection

Combined with the research on natural infection of COVID-19, including this study in Israel, how should we view the immune protection brought by the natural infection of COVID-19?

First of all, the natural infection of COVID-19 may indeed bring good protective effects, but more relevant research is still needed. Before the Israeli study came out, studies showed that neutralizing antibodies could still be detected in recovered patients 8 months after the infection, and another study showed that plasma cells closely related to long-term immunity were formed in patients with COVID-19 infection. These all indicate that the immunity brought by the COVID-19 infection is likely to be long-term and efficient.

However, other studies have shown that the immune response gap between the recovered patients is very large. For example, there are more antibodies in the severely ill patients, and some mildly ill patients have fewer or even undetectable antibodies. The Danish study mentioned above also shows that the protective effect of natural infection on the elderly has declined significantly. Therefore, this Israeli study should not be regarded as a conclusive conclusion on immunity to natural infections. We still need to continue to study the degree of protection of the survivors, especially whether there are differences in different groups of people, different mutations, and so on.

Secondly, both Israeli studies and British studies have confirmed that natural infections have a protective effect, and they all show that vaccinating the COVID-19 vaccine on this basis can further improve the protective effect. This is also something that must be taken into consideration when discussing natural immunity. Since vaccination can further improve the protective effect, the immunity brought by infection should obviously not be regarded as an unattainable peak. It is impossible to say that the survivors do not need to be vaccinated.

Finally, more recently, the results of these studies have shown the strength of the COVID-19 vaccine today. Don’t think that natural infection immunity is a low standard. In fact, in the history of all human vaccine development, this is a very high benchmark. The COVID-19 is a new type of virus that jumped from animals to humans not long ago. Such a virus has not evolved through long-term coexistence with the human immune system and is completely unfamiliar to the immune system. The more unfamiliar things tend to have the stronger immunogenicity to the immune system. Under this background, the human body’s immune response to the new coronavirus is very intense, and the vaccine can be compared with it. Even if it is really inferior, it is an amazing performance.

Many vaccines show very little difference in effectiveness whether they are in young or old people, whether they are healthy people or have underlying diseases. This high degree of stability is also a manifestation of the strength of the COVID-19 vaccine.

More importantly, natural infections may require the virus to overwhelm the human body and cause trouble in the heavens before obtaining good immune protection against COVID-19. Nowadays, some vaccines are very effective, but people ask if the side effects are too great after a fever. To obtain excellent protection at a very small price, it can be said that it is the level of a soldier who is defeated without a fight.

Therefore, although we can refer to the immune advantages of natural infections and find ways to continue to improve the effectiveness of vaccines in future research and development, before discussing which is more powerful than the COVID-19 vaccine and natural infections, it is better to consider the two. What is the price. The Israeli study is said to be the largest comparison between natural infections and the COVID-19 vaccine to date, but I believe that those who were infected with the COVID-19 living in the ICU or who unfortunately lost their lives in the epidemic must not be included in the statistics.

Reference materials:

https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1.full-text
https://www.nejm.org/doi/full/10.1056/NEJMoa2110475?query=featured_home
https://www.ndm.ox.ac.uk/files/coronavirus/covid-19-infection-survey/finalfinalcombinedve20210816.pdf
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00575-4/fulltext
https://www.nejm.org/doi/full/10.1056/NEJMoa2103055

(source:internet, reference only)

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