Vol.12 (August 2020, 8) "With Corona" Antibody testing at our clinic / Cluster analysis results / Latest vaccine development status / etc.

[1] About antibody testing at our clinic

The antibody tests conducted at our clinic's medical checkups and outpatient clinic (from June 6th to July 15th) showed that the antibody positivity rate was 7%, or 14 out of 405 cases. The tests were conducted on people who had no symptoms such as fever or cough (and had not had any within the past two weeks), but a positive antibody test still suggests that there are many asymptomatic infections.
Currently, our clinic offers PCR tests in addition to antibody tests in a safe environment, and we are considering antigen tests in the future.
We are working hard to provide safe medical care in the COVID-19 era.

Source: Ministry of Health, Labor and Welfare website "Domestic outbreak situation, etc."
https://www.mhlw.go.jp/stf/covid-19/kokunainohasseijoukyou.html#h2_1

The graph above shows the number of new positive cases in Japan by day. The number has been increasing clearly since late June.
According to Takahashi Yoshiaki (Chief Researcher, Nakasone Peace Institute), in "The reality and causes of the spread of infection from Shinjuku, which has become the epicenter (JBpress, July 2020, 07)," "The cumulative number of infected people living in Shinjuku Ward reached 21 per 7 as of July 19. In other words, this means that 10 in every 422.1 residents is infected, exceeding the infection rate in Italy (240)."

[2] The virus in Japan continues to mutate: results of cluster analysis

Genetic mutations of the new coronavirus have been pointed out as the reason behind the increasing number of new positive cases in Japan since late June.

Regarding COVID-1 in Japan, research by the center has already revealed that the virus strain originating from Wuhan, China, which arrived in January and February has subsided, and that the outbreak was caused by a European strain of the virus that was brought into the country in March by people returning from overseas.

Based on the results up to July 7, the current outbreak appears to have started as a cluster that emerged in mid-June, and may have subsequently spread across the country due to people's movements, such as business trips.

Additionally, the viral genome of the cluster that is the source of the current epidemic had mutated by six bases from the European strain that was identified in Japan in mid-March. The genome of the new coronavirus is estimated to mutate at a rate of two bases per month, and this timing matches up with the mutations. As no clear "connecting" patients or clusters have been identified in these three months, it is believed that the infection was continuing without being discovered as patients due to mild symptoms or asymptomatic cases.

"The origin of the virus strain is believed to be connected to the European virus strain that was brought into the country in March," said center director Makoto Kuroda.

The aim of investigating the virus genome is to support active epidemiological investigations. Using base mutations as a foothold, clusters are identified based on genomic information. In its report, the center noted that such molecular epidemiology "does not name specific regions or industries," and that "no evidence has been obtained to identify types that originate in specific regions, such as the Tokyo type or Saitama type."

Source: "Spread of infection: Originally from Europe imported in March, cluster in June spread nationwide, National Institute of Infectious Diseases analysis"
Mainichi Shimbun / August 2020, 8
https://news.yahoo.co.jp/articles/cc3773a32634d71943b431fee79cd362604e1850

The announcement from the National Institute of Infectious Diseases, which served as the basis for this report, also pointed out the following:

From late June, partial economic reopening began on the premise of taking sufficient infection control measures, but it is speculated that clusters emerged from groups of infected people that did not subside, and that local business trips and other factors may have been one of the factors that led to the spread of the virus not being contained in Tokyo but across the country.

Source: National Institute of Infectious Diseases: Genomic Molecular Epidemiology Survey of the Novel Coronavirus SARS-CoV-2 XNUMX (including figures)
https://www.niid.go.jp/niid/ja/basic-science/467-genome/9787-genome-2020-2.html

[3] From the blog of Mohan Chellappa of Johns Hopkins International

John Hopkins, a US hospital famous for its global COVID-19 statistics, is calling for global solidarity to overcome this crisis. The article was written by Dr. Mohan Chellappa, a doctor who has helped us in various ways for the 10 years since the Midtown Clinic opened.

Together Is the Only Way Through This Crisis

Together Is the Only Way Through This Crisis

Jul 14, 2020 | posted by Mohan Chellappa | Collaboration, Health Innovation, Health System Sustainability |No comments

[4] The current state of vaccine development around the world

The New York Times has summarized the development status of "vaccines" that are attracting attention from all over the world.
So far, one has received limited approval and seven have progressed to Phase 3 trials, the final phase before approval. A vaccine being developed by Japan's AnGes company is currently undergoing Phase 2 trials.

● Phase 2 trials completed; limited use permitted

Chinese company CanSino, in collaboration with the Institute of Biology of the Chinese Academy of Military Medical Sciences, has created a vaccine using adenovirus (Ad5), which generated strong immune responses in Phase 2 trials and was given permission for use by the Chinese military.

Phase 3 trials

Moderna, a US company, will begin phase 7 trials of a vaccine using messenger RNA in collaboration with the NIH on July 27, and plans to administer it to 3 people in the US. It has already received financial support of 3 billion yen.

Germany's BioNTech, the US's Pfizer, and China's Fosun Pharma have developed a vaccine that uses messenger RNA, and announced in July that the results of phase 7 and 1 trials were good. On July 2, they announced that they would begin phase 7 and 27 trials on 3 people in the US, Argentina, Brazil, and Germany. The US has signed a contract for 2 million doses, and Japan has also signed a contract for 3 million doses. They expect to produce 6 billion doses of the vaccine by the end of 1.2.

AstraZeneca has developed a vaccine using chimpanzee adenovirus (ChAdOx1) in collaboration with the University of Oxford in the UK, and confirmed safety and immune response in Phase 1 and 2 trials. Phase 2 and 3 trials have begun in the UK, India, Brazil, and South Africa. AstraZeneca aims to supply emergency vaccines in October, and has stated that it will have a supply system of 10 billion doses if approved.

The Wuhan Institute of Biological Products, in collaboration with state-run Sinopharm, has created an inactivated virus vaccine that is undergoing Phase 3 trials in China and the United Arab Emirates and is expected to be available for public use by the end of the year.
Sinopharm is also working with the Beijing Institute of Biological Products to create a second inactivated virus vaccine, which is also undergoing Phase 2 trials in China and the United Arab Emirates.

Sinovac Biotech, a private Chinese company, has created an inactivated virus vaccine (CorobnaVac), which completed phase 7 and 3 trials in July and is currently undergoing phase 1 trials in Brazil. It has an annual production capacity of XNUMX million doses.

Phase 3 trials of BCG are underway at the Murdoch Children's Research Institute in Australia.

Phase 1 and 2 trials

On June 6, AnGes announced that it has begun clinical trials of a DNA vaccine developed in collaboration with Osaka University and Takara Bio.

Source: "Coronavirus Vaccine Tracker," The New York Times
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html

[5] Professor Kodama’s “immunity passport” is impossible

The fact that a large-scale survey will be conducted using antibody tests for the new coronavirus infection isPrevious articleIt is still not clear how antibody tests can be used to ensure daily safety and security.
Professor Emeritus Tatsuhiko Kodama of the University of Tokyo's Research Center for Advanced Science and Technology, and chair of the Advisory Council for the COVID-19 Antibody Testing Machine Users Council, talks about the significance of antibody testing and how to make use of the testing system.

How do you plan to use antibody tests?

Kodama: We are proposing to use it for epidemiological surveys. We will find units with many people who test positive for antibodies. Since there is a possibility that the infection is spreading in those units, we will then conduct PCR tests on each individual person to find not only symptomatic COVID-19 patients, but also asymptomatic infected individuals.

This is different from an "immunity passport," which is an antibody test conducted for epidemiological surveys and determines whether an individual is able to live a normal life if they have antibodies.
Our survey revealed that, among those with mild symptoms or no symptoms, 0-30% of PCR positive individuals test negative for antibodies. We believe that on average, about 2% of individuals may test negative for antibodies.

──So there are a certain number of cases where antibody titers do not rise, mainly in mild cases and asymptomatic cases, meaning that even if antibody tests are negative, PCR tests are positive. If as many as 30% of cases exist, the "immunity passport" concept is impossible. By the way, what does it mean that "antibody titers do not rise"?

Kodama: One scenario is that the virus is eliminated by cellular immunity. If infection can be prevented at the cellular immunity stage, there is no need to mobilize humoral immunity, which is the production of antibodies.

Another scenario is when the immune response is weak and the person is unable to recognize the antigenicity of the virus. If there is no immune response, there will be no symptoms and the person will not become seriously ill. However, the virus will multiply in the body and spread. This is what we call a spreader. In this case, the problem is that the person will spread the virus.

--If there is no immune response, the person will not complain of symptoms.

Kodama: It is the host's immune response that makes COVID-19 more severe.
When antibodies are measured in COVID-19 patients, IgM and IgG antibodies increase almost simultaneously.
The coronavirus family has a high degree of nucleic acid homology. SARS-CoV-2 is 80% identical to the SARS virus and 50% identical to the common cold coronavirus. This activates immune memory. When there is immune memory, IgM and IgG antibodies usually rise at the same time.

The positive side is that infection can be controlled through cross-immunity. The low mortality rate of COVID-19 in East Asia is likely due to cross-immunity against cold coronaviruses that have previously infected people.
A typical example of the negative side is antibody-dependent enhancement (ADE).

In addition, SARS-CoV-2 is known to mutate very quickly. If this happens, for example, even if the body is able to produce neutralizing antibodies that are effective against SARS-CoV-2 that is prevalent at one time, the virus may mutate in the next season, and the neutralizing antibodies may no longer be effective.

--It seems like mutations occur quickly.

Kodama: Even within a single patient, genome mutations are occurring. This tendency for mutations to occur is a characteristic of the virus, but I think it may also be affecting patient trends. When you look at the number of patients in Japan, doesn't it suddenly increase and then suddenly decrease? I feel that problems with the virus itself are also affecting it.

In other words, because mutations are occurring rapidly, a virus that is highly infectious to humans spreads rapidly, but then the virus also mutates, its infectivity naturally weakens, and the number of patients drops rapidly.

My opinion is that it depends on the virus and cannot be predicted by humans. However, I think that an emergency response is necessary, and as long as it is effective against this year's virus, it makes sense to develop a vaccine. We can think later about whether it will be effective for the next season.

──So, countermeasures against COVID-19 could be a long-term battle.

Kodama: I would like to say that there must be a smarter way. As a 21st century response, we are proposing to conduct antibody tests for epidemiological surveys in each unit to identify asymptomatic individuals, and PCR tests to identify infected individuals in areas with many antibody positive individuals, and then provide optimal interventions for that group. Meanwhile, groups without infected individuals are allowed to live their lives as usual (Figure 3).

Figure 3: Positioning of the test recommended by the COVID-XNUMX Antibody Testing Machine Users Council

Source: "There is no such thing as an 'immunity passport', but... ~ Interview with Tatsuhiko Kodama, Professor Emeritus at the Research Center for Advanced Science and Technology, University of Tokyo," Nikkei Medical, July 2020, 07
https://medical.nikkeibp.co.jp/inc/mem/pub/report/t344/202007/566487.html

[6] Dr. Takao Oki’s proposal: “The new coronavirus is not scary for Japanese people”

Based on Dr. Kodama's point that COVID-42 countermeasures could be a long-term battle, I would like to conclude by introducing the contents of a presentation given by Dr. Oki Takao, Director of the Department of Surgery at the Jikei University School of Medicine and Special Assistant to the Director of the Hospital for COVID-XNUMX, at the XNUMXnd Council on Investments for the Future held at the Prime Minister's Official Residence, on how we should approach COVID-XNUMX, based on Dr. Kodama's point that COVID-XNUMX countermeasures could be a long-term battle. I feel a strong sense of empathy for his approach, which is to think about ways to coexist with COVID-XNUMX.

Regarding COVID-19 infection (novel coronavirus)

2) The state of emergency and stay-at-home orders imposed a huge burden on the economy and national finances, and although they did temporarily reduce the number of COVID-2 patients, the effect only lasted for two months. This must never be repeated.

2) We need to change our thinking from the unrealistic idea of ​​"containing the new coronavirus" to "coexisting with the new coronavirus."

100) COVID-XNUMX is a frightening infectious disease in the West, but for some reason, for Japanese people, COVID-XNUMX is not scary because it is a disease similar to seasonal influenza. This is clear from the experience and data of the past six months, such as the fact that the number of deaths per capita in Japan is about one-hundredth of that in the West and that there has been no overshoot. Therefore, the experience and policies of the West, and the WHO's views based on them, are often of no use to Japan. Japan needs to take its own unique measures.

0.1) Based on antibody tests (1%-3%) and PCR tests (0.02-0.04%) conducted so far on the general public, it is believed that there are already millions of infected people in Japan, which is proof that there are many asymptomatic patients. Therefore, the mortality rate is around XNUMX-XNUMX%, the same as that of seasonal influenza.

2020) In Japan, COVID-41 ranked 900st (about 3000 deaths) in the ranking of causes of death in the first half of 37. Seasonal influenza, which kills about XNUMX people every year, ranked XNUMXth.

9) However, there is a risk of the collapse of the medical system from another perspective. Japan has the lowest number of doctors per capita and the ratio of medical expenses to GDP among the G30 countries. For this reason, the collapse of the medical system, typified by the passing of emergency patients, has been a cause for concern even before COVID-XNUMX. Now that COVID-XNUMX has been added to the mix, there is a small capacity to absorb the burden. XNUMX% of hospitals that have accepted COVID-XNUMX patients are in the red, and although COVID-XNUMX is not something to be feared, if things continue as they are, "COVID-XNUMX will be passed around." Therefore, by providing bold financial support to hospitals that are dealing with COVID-XNUMX, the threshold for the collapse of the medical system can be significantly raised by turning COVID-XNUMX from a "bad luck draw" to a "lucky draw" for hospitals, and the public can run the economy with peace of mind. In addition, Jikei University of Medicine, which has responded to COVID-XNUMX sincerely through thorough zoning and other measures, is expected to incur a deficit of XNUMX billion yen this year, putting it at risk of collapse.

20) The number of deaths due to nosocomial infections in elderly care facilities and hospitals accounts for 40-XNUMX% of all deaths, so protecting these vulnerable groups can further reduce the mortality rate. Therefore, PCR tests should be conducted once a week on facility and hospital staff, along with patients admitted at public expense.

11) COVID-19 is designated as a Class 2 infectious disease, so if a PCR test is positive, isolation is required, which is unnecessarily straining public health centers and medical care. It is expected that the number of moderate to severe cases, mainly among the elderly, will gradually increase in the future. Another key to preventing the collapse of the medical system will be to avoid hospitalizing asymptomatic and mildly ill patients as much as possible, to always have spare COVID-19 beds, and to establish a system that specializes in hospitalization of patients who need treatment. If a patient becomes infected and develops symptoms, they can be seen and hospitalized at any time, which will ensure the public's peace of mind.

12) The only way to prove beyond doubt that the COVID-19 virus is at the same level as seasonal influenza is to calculate the "true number of patients" and "true mortality rate," and PCR tests should be conducted more widely on the general public. The virus should be downgraded from a "Class 2 infectious disease" as soon as possible. In addition, antibody tests are not useful when Japanese people expel the virus through natural immunity, because acquired immunity and antibodies are not mobilized.

13) In conclusion, the new coronavirus is not scary for Japanese people. We should educate the public about this, not get too excited or upset about the "number of new positive cases" that do not cause any real harm, provide financial support to hospitals that are dealing with the new coronavirus, and remove the designation as a Class 2 infectious disease to prevent the collapse of the medical system. We should take advantage of this "privilege of Japan," continue to adhere to basic infection control measures, and prioritize the lives and economy of the people.

Source: Excerpt from Document 42 of the XNUMXnd Future Investment Council, "Japan Economic Revitalization Headquarters/Future Investment Council" of the Prime Minister's Office
Summary of Takao Ohki's remarks at the 42nd Council on Investments for the Future
Jikei University School of Medicine Chief of Surgery and Special Assistant to the Director for COVID-19, Takao Oki
http://www.kantei.go.jp/jp/singi/keizaisaisei/miraitoshikaigi/dai42/siryou4.pdf