Dr. Ferguson of Imperial College is wrong. Dr. Levitt and Dr. Miyasaka are right. There is "prior immunity".
I was so impressed by Dr. Levitt's interview. He is totally right. This epidemic was never exponential, only sub-exponential. His word of "prior immunity" is the key. This is a huge difference and Dr. Levitt pointed out immediately after Dr. Ferguson published his simulation. It's a single-digit mistake.
Nobel prize-winning scientist: the Covid-19 epidemic was never exponential - The Post
https://unherd.com/thepost/nobel-prize-winning-scientist-the-covid-19-epidemic-was-never-exponential/
I tried to tell Dr. Levitt that "prior immunity" can be hugely different from BCG/TB and this may be causing the huge difference by country. But, no response.
https://twitter.com/j_sato/status/1256924383974526976
(Added on 28 May)
Below is the chart Dr. Miyasaka used in his Facebook post. I totally agree.
Today(16 May), I read a very important article by the immunologist, Dr. Miyasaka. He challenges the current herd immunity model that only takes into account acquired immunity/antibodies. I totally agree. This is the fundamental flaw of Dr. Ferguson's modeling. As the article is in Japanese, please use your translation tool or read the translation by DeepL.
一般に信じられている集団免疫理論はどこがおかしいのか免疫の宮坂先生に尋ねてみました（上）
https://news.yahoo.co.jp/byline/kimuramasato/20200516-00178807/
We asked Dr. Miyasaka of the Department of Immunology what is wrong with the commonly believed theory of herd immunity (1/2)
Masato Kimura - International Journalist in the UK
Sat, 16 May, 13:58
The mathematical model of infectious diseases is based on population immunity theory. However, if the number of people infected with the new coronavirus and carrying antibodies increases to a certain extent, will these people become a barrier and the epidemic will really come to an end?
We asked Professor Masayuki Miyasaka of the Frontier Research Center for Immunology at Osaka University, a leading expert in immunology who has become well known on television, via videophone.
Kimura:On the 15th, Minister of Health, Labor and Welfare Katsunobu Kato revealed that the positive rate of antibodies against the new coronavirus was 0.6% in 500 blood samples donated in Tokyo and 0.4% in 500 samples donated in six prefectures in the Tohoku region.
I hear that a large-scale antibody survey will be conducted next month, but what does it mean?
Miyasaka: We haven't made public which kit was used. Some antibody test kits have poor accuracy and sensitivity. The positive rate in this case came out quite low, and I think it's difficult to interpret.
A paper that came out recently looked at 14 different antibody testing kits and found that only three could be used satisfactorily. In other words, the antibody test kits are very poor in terms of accuracy and sensitivity at this stage. The kit that comes out with a high rate of positivity hooks up the nasal cold corona.
The reason for the low positive rate is due to poor sensitivity and, in the case of the new coronavirus, due to very poor immunity. The antibodies don't come up easily and the amount is low.
Previous papers have looked at the formation of antibodies and the severity of the disease. If only good antibodies (good antibodies) were produced, then the rate of severe disease should not decrease as antibodies appear and increase.
However, in many cases, the rate of severe disease is also increasing, even though the level of antibodies is increasing. On the other hand, it is people with mild illnesses who have low levels of antibodies.
There are at least three types of antibodies. In SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome), it has been reported that bad antibodies are produced along with good antibodies.
In the case of HIV (human immunodeficiency virus), all the antibodies that can be produced are useless antibodies, and no matter how many antibodies are produced, they do not kill the virus.
These unassisted antibodies are also produced in the new coronaviruses. Therefore, simply looking at the amount of antibodies, it is hard to know how much of the correct immunity is really developed.
Mr. Miyasaka (Courtesy of him)
Then there is a way to measure only the good antibodies.
A neutralizing antibody assay is it. There is a test to determine how much the infection is suppressed if antibodies coexist in the cells when the virus is injected into cultured cells in a test tube, and the ability to neutralize the degree of virus infection.
This measurement can only be made at Biosafety Level 3. It can only be done where you have cultured cells and the virus is being cultured. Normal laboratories cannot do this.
Regular laboratories simply measure the amount of antibodies that bind to the virus. In the case of the new coronavirus, it is thought that all three types of antibodies may have been produced. That's the problem with antibody testing kits.
We only measure the amount of antibodies, not their function.
In the case of HIV, even if antibodies can be produced, they are all useless antibodies, so a vaccine is not yet available. This can happen even with new coronaviruses.
From what we have seen so far, the new coronavirus has a weak way of making antibodies and the timing is slow. It comes down to the question of whether it is OK to measure only antibodies.
In terms of the PCR positive rate, it is less than 10% in Tokyo (author's note: cumulative total is 9.5% in Tokyo and 6.9% in Japan).
In Germany, where so many PCR tests are performed, the positive rate is about 6% (author's note: 5.6%), which is about 6 out of 100 people. Considering this, there are probably a few more or less infected people in Tokyo as well.
However, if you look at the antibodies, it could come out a little higher. This is because with the current antibody test kits, there is a possibility that the nasal cold corona may be trapped. Apparently, the numbers that come out don't seem very credible.
On the other hand, an antibody test kit recently released by Roche in Switzerland has a sensitivity of 99%. It's also very accurate, so I think if you use something like that, you can see what percentage of people are infected in today's society.
The Pasteur Institute reports that only 4.4% of people were infected when they checked in France, and even in Paris, where the infection was most widespread, it was 9-10%. It was 5% in Spain as well, he said.
There were questions about which antibody test kit was used and how sensitive it was, but the media was of the opinion that only a few percent of the patients were infected and that this virus does not build up collective immunity well.
Apparently, this virus is very weak in its ability to cause immunity, and when it does, it's slow. Looking only at antibodies, it is very difficult to judge.
Until now, collective immunity has been judged only on the basis of the parameters of acquired immunity and also on the basis of antibodies, but I think this is wrong.
The body's defense against viruses is not defined only by acquired immunity, but also by our immunity, which is a two-stage system of innate and acquired immunity.
If your natural immunity is strong, you may be able to fight off the virus even if your acquired immunity doesn't work.
Since natural immunity alone can sometimes fight off viruses, you may not be able to determine if you have collective immunity just by looking at the amount of antibodies or the positive rate. Maybe that's what's happening this time around.
Kimura: I don't know if it's appropriate to compare humans to livestock, but the terrible thing is the lesson of foot-and-mouth disease.
In the UK, 6.5 million livestock have been slaughtered in response to foot-and-mouth disease, based on a mathematical model of the new coronavirus, developed by Professor Neil Ferguson of Imperial College London.
The foot-and-mouth disease virus has also mutated repeatedly, and the vaccine is not foolproof. Although the lethality of new coronaviruses is not as high, the economic, social, and political costs are immeasurable.
It seems to me that we have to be prepared for a nightmare scenario.
Miyasaka: The problem is the way we think about population immunity. This is a calculation of "what percentage of a particular population will be immunized to stop an infectious epidemic," not an indication of what percentage of people will die if they are not immunized.
That's where I think it's being used incorrectly.
Assuming a basal reproduction number (Ro) of 2.5 in the new corona, the population immunity threshold is (1-1/2.5)x100 = 60%, suggesting that 60% of people need to retain immunity to stop the epidemic.
It should be noted, however, that in this case, it is implicitly understood that "immunity" generally refers to the formation of antibodies and that it is "acquired immunity".
However, at the individual level, defense against viruses is a two-step process, and innate and acquired immunity are involved in viral exclusion.
If innate immunity works well, even if a small number of virus particles invade, innate immunity alone may be able to eliminate the virus. This means that even if acquired immunity doesn't work, the virus may be able to be eliminated.
In fact, recent studies have shown that innate immunity can be trained and strengthened by a variety of stimuli.
For example, it has been pointed out that BCG, a tuberculosis vaccine, not only increases immunity against tuberculosis bacteria, but also increases the ability to respond to common bacteria and viruses, suggesting that BCG strengthens and trains innate immunity as a mechanism of action.
To illustrate this possibility, a Dutch research group is looking at the frequency of transient viremia that appears after BCG vaccination with the live yellow fever vaccine.
BCG vaccination significantly reduced the incidence of viremia (without the involvement of acquired immunity), suggesting that trained and enhanced innate immunity can result in biological defense against viruses even in the absence of acquired immunity.
In other words, when we talk about population immunity, we need to take into account both innate and acquired immunity working at the individual level, and not just acquired immunity.
In the case of the new coronavirus, as mentioned above, it is believed that about 60% of people need to remain immune in order to stop an epidemic, but is that really the case?
For example, in Wuhan City in Hubei Province, China, where there have been severe epidemics in the past, and on the cruise ship Diamond Princess, only about 20% of the people were infected. It has not been observed that as much as 60% of the population gets infected.
The reason for this is that when a major epidemic begins, people begin to take quarantine measures and restrict contact, and with that, the basic reproduction number mentioned above decreases (this is called the effective reproduction number).
If the R-value is lowered to 1.2 by contact restriction, the population immunity threshold is less than 20% (author's note: 16.7%) according to the above formula. I suspect that this is what was actually happening in Wuhan City and the Diamond Princess.
This means that while some people may have used both innate and acquired immunity to fight off the virus in the form of subclinical infection, a significant number of people may have used only innate immunity to fight off the virus.
It is therefore possible that many people have fought off the virus before the infection was established.
As more sensitive and accurate antibody measurement kits come out, we will be able to determine the validity of this idea when we can see what percentage of people really acquire antibodies (infected or not).
Secondly, the idea of collective immunity has been used to support this idea: "Since we are not immune to this virus, if the infection spreads in an unprotected state, about 60% of the people in the population will be infected.
In fact, Professor Ferguson in the UK, the Swedish epidemiologist Anders Tegener, and Professor Hiroshi Nishiura of Hokkaido University's Graduate School of Medicine, the Ministry of Health, Labour and Welfare's cluster countermeasures team, also cited these figures.
However, I think this assumption is different. As mentioned above, this has not happened in Wuhan City or Diamond Princess. This hasn't happened in Spain or Italy.
In times of major infections, people always take strong traffic control measures, such as urban blockades, so that infections are suppressed and the number of effective reproductions goes down. They then settle for a much lower population immune threshold than expected.
The immunity caused by this virus is not very high and seems to be short-lived, so from an immunologist's point of view, a situation in which as much as 60% of the population becomes immune is unlikely to happen unless a very good vaccine comes out.
There is no denying the possibility that they did not encounter the virus. But the virus spread even before the introduction of urban blockades and social distances.
Nevertheless, we have not had a situation where 60% of the population would be infected if no measures were taken, as Professors Ferguson and Nishiura have said.
I believe that Professor Nishiura's theory itself is correct, but the assumption that 60% of the population will be infected by this virus and hundreds of thousands of people may die if no countermeasures are taken is wrong.
I don't know which is right, but when a good antibody test kit comes out we'll find out if only 20% of the people really got infected.
Translated with www.DeepL.com/Translator (free version)
Nobel prize-winning scientist: the Covid-19 epidemic was never exponential - The Post
https://unherd.com/thepost/nobel-prize-winning-scientist-the-covid-19-epidemic-was-never-exponential/
I tried to tell Dr. Levitt that "prior immunity" can be hugely different from BCG/TB and this may be causing the huge difference by country. But, no response.
https://twitter.com/j_sato/status/1256924383974526976
(Added on 28 May)
Below is the chart Dr. Miyasaka used in his Facebook post. I totally agree.
Today(16 May), I read a very important article by the immunologist, Dr. Miyasaka. He challenges the current herd immunity model that only takes into account acquired immunity/antibodies. I totally agree. This is the fundamental flaw of Dr. Ferguson's modeling. As the article is in Japanese, please use your translation tool or read the translation by DeepL.
一般に信じられている集団免疫理論はどこがおかしいのか免疫の宮坂先生に尋ねてみました（上）
https://news.yahoo.co.jp/byline/kimuramasato/20200516-00178807/
We asked Dr. Miyasaka of the Department of Immunology what is wrong with the commonly believed theory of herd immunity (1/2)
Masato Kimura - International Journalist in the UK
Sat, 16 May, 13:58
The mathematical model of infectious diseases is based on population immunity theory. However, if the number of people infected with the new coronavirus and carrying antibodies increases to a certain extent, will these people become a barrier and the epidemic will really come to an end?
We asked Professor Masayuki Miyasaka of the Frontier Research Center for Immunology at Osaka University, a leading expert in immunology who has become well known on television, via videophone.
Kimura:On the 15th, Minister of Health, Labor and Welfare Katsunobu Kato revealed that the positive rate of antibodies against the new coronavirus was 0.6% in 500 blood samples donated in Tokyo and 0.4% in 500 samples donated in six prefectures in the Tohoku region.
I hear that a large-scale antibody survey will be conducted next month, but what does it mean?
Miyasaka: We haven't made public which kit was used. Some antibody test kits have poor accuracy and sensitivity. The positive rate in this case came out quite low, and I think it's difficult to interpret.
A paper that came out recently looked at 14 different antibody testing kits and found that only three could be used satisfactorily. In other words, the antibody test kits are very poor in terms of accuracy and sensitivity at this stage. The kit that comes out with a high rate of positivity hooks up the nasal cold corona.
The reason for the low positive rate is due to poor sensitivity and, in the case of the new coronavirus, due to very poor immunity. The antibodies don't come up easily and the amount is low.
Previous papers have looked at the formation of antibodies and the severity of the disease. If only good antibodies (good antibodies) were produced, then the rate of severe disease should not decrease as antibodies appear and increase.
However, in many cases, the rate of severe disease is also increasing, even though the level of antibodies is increasing. On the other hand, it is people with mild illnesses who have low levels of antibodies.
There are at least three types of antibodies. In SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome), it has been reported that bad antibodies are produced along with good antibodies.
In the case of HIV (human immunodeficiency virus), all the antibodies that can be produced are useless antibodies, and no matter how many antibodies are produced, they do not kill the virus.
These unassisted antibodies are also produced in the new coronaviruses. Therefore, simply looking at the amount of antibodies, it is hard to know how much of the correct immunity is really developed.
Mr. Miyasaka (Courtesy of him)
Then there is a way to measure only the good antibodies.
A neutralizing antibody assay is it. There is a test to determine how much the infection is suppressed if antibodies coexist in the cells when the virus is injected into cultured cells in a test tube, and the ability to neutralize the degree of virus infection.
This measurement can only be made at Biosafety Level 3. It can only be done where you have cultured cells and the virus is being cultured. Normal laboratories cannot do this.
Regular laboratories simply measure the amount of antibodies that bind to the virus. In the case of the new coronavirus, it is thought that all three types of antibodies may have been produced. That's the problem with antibody testing kits.
We only measure the amount of antibodies, not their function.
In the case of HIV, even if antibodies can be produced, they are all useless antibodies, so a vaccine is not yet available. This can happen even with new coronaviruses.
From what we have seen so far, the new coronavirus has a weak way of making antibodies and the timing is slow. It comes down to the question of whether it is OK to measure only antibodies.
In terms of the PCR positive rate, it is less than 10% in Tokyo (author's note: cumulative total is 9.5% in Tokyo and 6.9% in Japan).
In Germany, where so many PCR tests are performed, the positive rate is about 6% (author's note: 5.6%), which is about 6 out of 100 people. Considering this, there are probably a few more or less infected people in Tokyo as well.
However, if you look at the antibodies, it could come out a little higher. This is because with the current antibody test kits, there is a possibility that the nasal cold corona may be trapped. Apparently, the numbers that come out don't seem very credible.
On the other hand, an antibody test kit recently released by Roche in Switzerland has a sensitivity of 99%. It's also very accurate, so I think if you use something like that, you can see what percentage of people are infected in today's society.
The Pasteur Institute reports that only 4.4% of people were infected when they checked in France, and even in Paris, where the infection was most widespread, it was 9-10%. It was 5% in Spain as well, he said.
There were questions about which antibody test kit was used and how sensitive it was, but the media was of the opinion that only a few percent of the patients were infected and that this virus does not build up collective immunity well.
Apparently, this virus is very weak in its ability to cause immunity, and when it does, it's slow. Looking only at antibodies, it is very difficult to judge.
Until now, collective immunity has been judged only on the basis of the parameters of acquired immunity and also on the basis of antibodies, but I think this is wrong.
The body's defense against viruses is not defined only by acquired immunity, but also by our immunity, which is a two-stage system of innate and acquired immunity.
If your natural immunity is strong, you may be able to fight off the virus even if your acquired immunity doesn't work.
Since natural immunity alone can sometimes fight off viruses, you may not be able to determine if you have collective immunity just by looking at the amount of antibodies or the positive rate. Maybe that's what's happening this time around.
Kimura: I don't know if it's appropriate to compare humans to livestock, but the terrible thing is the lesson of foot-and-mouth disease.
In the UK, 6.5 million livestock have been slaughtered in response to foot-and-mouth disease, based on a mathematical model of the new coronavirus, developed by Professor Neil Ferguson of Imperial College London.
The foot-and-mouth disease virus has also mutated repeatedly, and the vaccine is not foolproof. Although the lethality of new coronaviruses is not as high, the economic, social, and political costs are immeasurable.
It seems to me that we have to be prepared for a nightmare scenario.
Miyasaka: The problem is the way we think about population immunity. This is a calculation of "what percentage of a particular population will be immunized to stop an infectious epidemic," not an indication of what percentage of people will die if they are not immunized.
That's where I think it's being used incorrectly.
Assuming a basal reproduction number (Ro) of 2.5 in the new corona, the population immunity threshold is (1-1/2.5)x100 = 60%, suggesting that 60% of people need to retain immunity to stop the epidemic.
It should be noted, however, that in this case, it is implicitly understood that "immunity" generally refers to the formation of antibodies and that it is "acquired immunity".
However, at the individual level, defense against viruses is a two-step process, and innate and acquired immunity are involved in viral exclusion.
If innate immunity works well, even if a small number of virus particles invade, innate immunity alone may be able to eliminate the virus. This means that even if acquired immunity doesn't work, the virus may be able to be eliminated.
In fact, recent studies have shown that innate immunity can be trained and strengthened by a variety of stimuli.
For example, it has been pointed out that BCG, a tuberculosis vaccine, not only increases immunity against tuberculosis bacteria, but also increases the ability to respond to common bacteria and viruses, suggesting that BCG strengthens and trains innate immunity as a mechanism of action.
To illustrate this possibility, a Dutch research group is looking at the frequency of transient viremia that appears after BCG vaccination with the live yellow fever vaccine.
BCG vaccination significantly reduced the incidence of viremia (without the involvement of acquired immunity), suggesting that trained and enhanced innate immunity can result in biological defense against viruses even in the absence of acquired immunity.
In other words, when we talk about population immunity, we need to take into account both innate and acquired immunity working at the individual level, and not just acquired immunity.
In the case of the new coronavirus, as mentioned above, it is believed that about 60% of people need to remain immune in order to stop an epidemic, but is that really the case?
For example, in Wuhan City in Hubei Province, China, where there have been severe epidemics in the past, and on the cruise ship Diamond Princess, only about 20% of the people were infected. It has not been observed that as much as 60% of the population gets infected.
The reason for this is that when a major epidemic begins, people begin to take quarantine measures and restrict contact, and with that, the basic reproduction number mentioned above decreases (this is called the effective reproduction number).
If the R-value is lowered to 1.2 by contact restriction, the population immunity threshold is less than 20% (author's note: 16.7%) according to the above formula. I suspect that this is what was actually happening in Wuhan City and the Diamond Princess.
This means that while some people may have used both innate and acquired immunity to fight off the virus in the form of subclinical infection, a significant number of people may have used only innate immunity to fight off the virus.
It is therefore possible that many people have fought off the virus before the infection was established.
As more sensitive and accurate antibody measurement kits come out, we will be able to determine the validity of this idea when we can see what percentage of people really acquire antibodies (infected or not).
Secondly, the idea of collective immunity has been used to support this idea: "Since we are not immune to this virus, if the infection spreads in an unprotected state, about 60% of the people in the population will be infected.
In fact, Professor Ferguson in the UK, the Swedish epidemiologist Anders Tegener, and Professor Hiroshi Nishiura of Hokkaido University's Graduate School of Medicine, the Ministry of Health, Labour and Welfare's cluster countermeasures team, also cited these figures.
However, I think this assumption is different. As mentioned above, this has not happened in Wuhan City or Diamond Princess. This hasn't happened in Spain or Italy.
In times of major infections, people always take strong traffic control measures, such as urban blockades, so that infections are suppressed and the number of effective reproductions goes down. They then settle for a much lower population immune threshold than expected.
The immunity caused by this virus is not very high and seems to be short-lived, so from an immunologist's point of view, a situation in which as much as 60% of the population becomes immune is unlikely to happen unless a very good vaccine comes out.
There is no denying the possibility that they did not encounter the virus. But the virus spread even before the introduction of urban blockades and social distances.
Nevertheless, we have not had a situation where 60% of the population would be infected if no measures were taken, as Professors Ferguson and Nishiura have said.
I believe that Professor Nishiura's theory itself is correct, but the assumption that 60% of the population will be infected by this virus and hundreds of thousands of people may die if no countermeasures are taken is wrong.
I don't know which is right, but when a good antibody test kit comes out we'll find out if only 20% of the people really got infected.
Translated with www.DeepL.com/Translator (free version)
I am a strong believer of your hypothesis. In appearance, most of media seems to bury the BCG hypothesis at present. In future, however, your analysis will get proper interest in future. Progress of real science needs much time beyond expectation of the people.
ReplyDeleteMacky, thanks for your compliment.
DeleteI wonder why most of media are still ignoring this hypothesis as it has more evidence of the results and how it works than lockdowns have...
I hope BCG, especially the Tokyo strain, can be approved as a non-specific vaccine and people can get back to normal life soon.
This comment has been removed by the author.
ReplyDeleteThis comment has been removed by the author.
ReplyDeleteHi Jun,
ReplyDeleteMy colleagues and I did an analysis of the excess mortality of famous people according to Wikipedia.
We also checked the correlation of mortality with BCG. We plan to update this study when May ends. If you are interested, we can tell you in detail.
Our main goal was to check the real increase in mortality in Russia, since the official statistics on mortality in Russia come out with great delay and possible censorship. And on Wikipedia, the data is independent, operational, and relevant. Perhaps these data will help to see some dependencies for countries with BCG and without BCG and to conduct additional tests of the hypothesis.
https://www.facebook.com/100001749973097/posts/2940803279321309/?d=n
https://www.facebook.com/100001749973097/posts/2980951158639854/?d=n
Hi Sergey,
DeleteThanks for your input. Russia seems to be catching up the East Europe countries two weeks behind in terms of death tolls.
One difference is that Russia seems to start testing massively and its cases have been growing more than the East Europe countries. I suspect this massive testing will produce massive false positive cases and they may be quarantined with real positive cases...
In the Russian media, BCG news was discussed on federal TV. Medical scientists even commented positively on this hypothesis.
DeleteBut then other media criticized the hypothesis, citing a weak methodology in a scientific article about BCG. A big contribution to this criticism was made by a journalist-biologist, who was then quoted in many Russian media:
https://www.facebook.com/irina.yakutenko/posts/10158061141514800
Now articles about the possible benefits of vaccines, including BCG, for the production of T-lymphocytes are starting to appear again.
And critics have not yet commented on this news.