Vol.18 (January 2021, 1) Antibody-positive patients at our clinic / Latest trends in Japan and the world / Preventing the collapse of the medical system / Cases where caution is required even if the PCR test is negative / Why vaccines are needed now, etc.

[1] About antibody-positive patients at our clinic

当クリニックでは発熱や咳などの症状がない（過去2週間以内にもなかった）方を対象に実施しておりますが、2020年12月15日から2021年1月14日までのコロナ抗体陽性率は4.06％（13/320）でした。
It's still an upward trend.
Since this does not include many people in their 20s and 30s, I think the realistic positive rate is probably over 5%.

The population of Tokyo is about 1,400 million. 5% is 70 people.
During the same period, the total number of PCR positive cases in Tokyo was 26,596. The total number of positive cases to date is 90,659.
Considering this, it would not be surprising if the number of asymptomatic COVID infections was 8-10 times higher than reported.
Antibody tests are well suited to monitoring the overall infection.

Figure 1: Trends in antibody testing at our clinic

[2] The situation in Japan and the world

Data current as of January 1th.
The number of new infections in Japan remains high, but there is some possibility that we may have seen the peak.

Figure 2: Number of new infections by day (Japan)

There is hope that there may be signs of a decline around the world.

Figure 3: Number of new infections by day (worldwide)

Source: https://news.yahoo.co.jp/pages/article/20200207

Here is a graph of new deaths so far from the Financial Times.
We can see that the majority of cases are in the US, the UK and Europe.

Figure 4: Total deaths (world)

New cases are compared between the US, UK and Japan. Note that this is a logarithmic graph.
We can see that Japan has fewer than those two countries.

Figure 5: Comparison of new cases: Japan, the US and the UK

So what about Asia?
Japan has far more than South Korea, China, Thailand and Singapore, and it even appears to be approaching India.

Figure 6: Comparison of new cases: Asia

Source: FINACIAL TIMES
Coronavirus tracker: the latest figures as countries fight Covid-19 resurgence | Free to read | Financial Times (ft.com)

[3] Proposal from Junichi Taguchi, Director of Tokyo Mid-Tau Clinic: “To prevent the collapse of the medical system”

I would like to offer some suggestions to prevent the collapse of the medical system.

[4] World leaders are sending a clear message to their citizens:

Chancellor Merkel's final New Year's Eve speech: "We know how to fight the virus."

In Germany, it is traditional for the chancellor to deliver a policy speech on New Year's Eve, and for Chancellor Merkel, who will retire after the 2021 general election, her speech on New Year's Eve 2020 was her last.

The annual speech usually outlines the agenda for the coming year, but last year's was dominated by talk of the pandemic.

Chancellor Merkel addressed the nation, expressing her sympathies to those affected by the misfortune of the coronavirus and her gratitude to those who are fighting the pandemic, while also saying that 15 had been the most difficult year of her 2020 years as chancellor.

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Dear Koreans,

What a year it has been!
2020 was a year of total surprise. An unknown virus entered our bodies and our lives. It infiltrated our most human behaviors: our intimate contacts, our hugs, our conversations, our celebrations. It made ordinary behaviors risky and unnatural precautions the norm.

2020, the year of the pandemic, has also been a year of learning. When we responded in the spring, we didn't have much knowledge or information, but we had no choice but to make decisions and hope that the results would be right.
The COVID-100 pandemic is a once-in-a-century political, social and economic challenge. This is a historic crisis that has asked a lot from all of us. Some of us have had to accept very difficult circumstances.
Facing this historic crisis will require a long period of trust and patience from all of us, and for that I am so grateful to you all. But at the end of this breathless year, we also need to pause, take a deep breath, and mourn.

As a society, we must never forget how many of us have lost loved ones, and how many were unable to be with them in their final moments.
I cannot ease their pain, but they are my soulmates tonight.
I can only imagine the grief that must be going through for those who have lost loved ones to the coronavirus, or the suffering that must be caused to those who are still suffering from the aftereffects of the disease.
There are those who dispute and deny the existence of the virus, but conspiracy theories are not only false and dangerous, they are also humiliating and distressing to those who are suffering from the virus.

2020 has been a year of worry and uncertainty, but it has also been a year in which many people have given of themselves without expecting anything in return.
First and foremost are the doctors, nurses, and caregivers working in hospitals, nursing homes, and other facilities. Then there are public health officials who continue to play a central role in the fight against the virus. And then there are our military, who have dedicated themselves to providing support when and where it was needed.
And it was thanks to countless people that our lives kept going despite the pandemic - in supermarkets, transport companies, post offices, buses and trains, police stations, schools and nurseries, churches, publishing companies.
I'm also grateful that most people are following the rules, wearing masks and keeping a distance from others. I believe this kind of behavior makes it possible to create a society that values ​​people. It shows consideration for others, the ability to know when to step back, and public spirit.
This attitude from millions of our citizens has helped us get through this pandemic, and it will be needed in the new year.

But I still see hope. In the past few days, vaccinations have already begun, first for the elderly, their caregivers and medical staff in intensive care. This is not just happening in Germany, but throughout Europe and the world. The number of vaccinations is increasing every day, and little by little, more and more people of all ages and professions will be able to be vaccinated. Eventually, everyone who wants to be vaccinated will be able to. I intend to get vaccinated when it's my turn.

Another thing that gives me hope are scientists around the world, and especially in Germany, who developed the first reliable coronavirus test and also the first vaccine that was approved in many parts of the world.
The vaccine is the result of research by a German company and is now produced in a German-American collaboration. Founders Ugur Şahin and Ezlem Türeç from Mainz say that people from 60 countries work at the company, demonstrating European and international collaboration - the power of diversity in delivering progress.
However, the pandemic continues to present very difficult situations. Many business owners, employees, freelancers and artists are worried about their livelihoods. Their difficult situation is not their fault, and the Federal Government will not abandon them. Government support is on an unprecedented scale. The short-time work benefit (a system in which the government compensates for the salaries of employees whose working hours and wages are reduced due to the pandemic) has also been extended. These measures will help protect jobs.

So will the new year be all about the coronavirus? No. There was much more to the story this year. Even before the pandemic, the world was changing rapidly and radically. That's why Germany increasingly needs to focus its energies and creativity to develop bold ideas for the future.
So that our economy, mobility and life will be climate-friendly. So that everyone in Germany has equal living conditions and benefits from equal educational opportunities. So that we as Europeans can fulfil our potential in a globalised and digitalised world.

Ladies and gentlemen, difficult days will continue in our country for some time. It is up to us to see how we get through this pandemic. The difficult winter is not over yet. We know how to fight the virus. Besides the vaccine, the most effective thing is our own actions. Each and every one of us has to follow the rules. All of us together.

Finally, on a personal note: In nine months' time there will be a federal election and I will not be standing. This will therefore be my last New Year's Eve speech as Federal Chancellor. It is no exaggeration to say that this year has been the most challenging in the last 9 years. And despite the fears and doubts, I have never welcomed a new year with more hope.

We sincerely hope that the New Year 2021 will bring you and your families good health, confidence and happiness.

Source: Courrier Japon [Full translation] Chancellor Merkel's final New Year's Eve speech: "We know how to fight the virus"

[Full translation] Chancellor Merkel's final New Year's Eve speech: "We know how to fight the virus" | She stands by those suffering from the infection and thanks the people for their efforts

(Full translation by Dr. Michiyuki Matsuzaki)

[5] Cases where caution is required even if the PCR test result is negative

If you have had obvious close contact or have cold symptoms such as fever, even if the PCR test is negative, the possibility of COVID-19 infection cannot be completely ruled out.
Please stay home for at least one week (two weeks if instructed by the public health center).

Figure 7: Probability of PCR negative if COVID-XNUMX infection is confirmed

The vertical axis is the PCR false negative rate (the rate at which PCR tests result in a negative result even though the person is actually infected).
① Up until the third day after infection, the false negative rate is close to 3%, meaning that there are almost no positive results.
②From the 5th to 12th day after infection, the false negative rate is 20-30%. In other words, the correct positive rate is 70-80%.

The following graph shows the probability that a person is actually positive when initially judged to be PCR negative, regardless of whether they have symptoms or not. Pretest probability is the PCR positivity rate in that area. Incidentally, recently, 10.5% of people who have taken PCR tests in both Tokyo and Osaka have been judged to be positive, so the dashed line at 11% on the graph applies.
As can be read from the graph, between 5 and 12 days after infection (close contact) (as indicated by the arrow), approximately 5% of people who test negative for PCR may actually be positive.

Figure 8: Probability of actually being positive when initially PCR-negative

Therefore, if you are determined to be a close contact, even if the PCR test is negative, the possibility cannot be denied that you are actually positive, so you will need to stay at home for at least 7 days (the public health center recommends 14 days) until you are almost no longer infectious.

Source: Ann Intern Med. 2020 Aug 18;173(4):262-267.
Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure
https://www.acpjournals.org/doi/10.7326/m20-1495

[1] China’s ultra-intensive PCR screening tests: Over 1000 million tests completed in one week

In mainland China, three positive cases were discovered in October last year, about two months after the previous case. Over the next five days, more than 10 million PCR tests were conducted. This case demonstrated the strength of China's medical system.

Three COVID-10 cases were discovered in Qingdao, China on October 11. Trained medical teams were immediately deployed and 3 testing centers were set up in and around Qingdao.
PCR tests were conducted using the pooling method, with close contacts being tested in groups of three, hospitalized patients and medical personnel in groups of five, and other people in groups of ten; in cases of positive results, each individual's sample was retested.
By October 10th, a total of 16 million people had been tested, and nine other positive cases had been found. By November, all testing had been completed.

Source: Rapid Response to an Outbreak in Qingdao, China
https://www.nejm.org/doi/full/10.1056/NEJMc2032361

[10] It will take XNUMX years for the new coronavirus to become a common cold

Here's an update from the news the other day.

A research team from Emory University in the United States has estimated that it will take about 4 years for the COVID-10 virus to become established in humans, just like the four existing types of human coronaviruses that cause the common cold. In 10 years' time, most people will be infected by the age of 3 to 5, and even if they are infected at an older age, they will be able to acquire immunity that prevents the virus from becoming severe, which could lead to a lower mortality rate than influenza.

The research team hypothesized that the new coronavirus has similar characteristics to the four human coronaviruses. They believed that if you are infected when you are young, you will only have mild symptoms, and if you are infected again, you will be less likely to develop severe symptoms. The main reason for the current increase in serious cases and deaths worldwide is that people are becoming infected for the first time when they are older.
Based on this, the team calculated future scenarios for COVID-1, taking into account the "basic reproduction number" (R0), which indicates the average number of people that one infected person infects in a population of people with no immunity, as well as data on four types of coronaviruses. As a result, it was revealed that if R4 is set at 0, it will take 2 years for most people aged 3, 4-5, and 1 to become infected. Because the severity of the disease is low in children, it is possible that vaccinations will no longer be necessary.
On the other hand, if the R0 is 4, it will take about two and a half years for the virus to become a childhood infectious disease and become established. Regardless of the R2 value, once the virus has become established, the mortality rate will drop dramatically, potentially even lower than that of seasonal influenza, which is about 0%.
The World Health Organization (WHO) estimates the R0 of COVID-1 to be between 4 and 2, with some reports putting it at even higher.
The research team said, "If the disease were severe in children, like MERS, a vaccine would be necessary, but that is not the case with COVID-19.
However, social distancing and vaccinations will remain important measures until the transition and establishment of the virus."

Source: Yahoo! News Mainichi Shimbun "New Corona will be just a common cold in 10 years, US university research team estimates" 1/18 (Mon)
https://news.yahoo.co.jp/articles/2da4c481124c82318c9e68c61d886b114ed0f39d

The original article on this news is from the Science magazine below. We will explain it in detail.

Figure 9: Infection mortality rate (IFR) and changes in age at infection and time elapsed

In A, the vertical axis represents the death rate after infection (IFR: Infection Fatality Ratio), and the horizontal axis represents the age at which the infection occurs.

The mortality rate for the COVID-2 virus (CoV-60), shown in red, increases slightly from around the age of 80, but even at age 5 it is only around XNUMX%.
We can see that other viruses, such as MERS (green line) and SARS (CoV-1: blue line), have a higher post-infection mortality rate.

The top graph in B shows the COVID-2 infection (CoV-10), with the vertical axis showing the death rate after infection (IFR: Infection Fatality Ratio) and the horizontal axis showing how many years from now (up to XNUMX years from now).

As estimated by the WHO, if the "basic reproduction number" (R1), which indicates the average number of people that one infected person infects in a population of non-immune people, is around 0, then in 2 years the IFR will be 10, as shown in the solid red line in the graph, meaning that the mortality rate after infection will be 0.001%.
By the way, for MERS in the bottom graph, the IFR after 10 years is 0.37, which means that the post-infection mortality rate is more than one in three.

It is important to note that the IFR includes people who have no symptoms and have not been diagnosed in hospital.
Therefore, the death rate is calculated by including the number of people who were infected unknowingly and then recovered through antibody tests, which is the large majority.

As shown in the positive rate data of our hospital's antibody tests in Chapter 1, 8% of people in the Tokyo area may be infected, which is nearly 10-XNUMX times the number of people who tested positive, so it is clear that the majority of people are undiagnosed.
The case fatality ratio (CFR) is the mortality rate of people who test positive for the virus by PCR or other tests, and in Japan it is 1.4% as shown in the table below. The IFR is much lower than the CFR.

As of January 1, the total number of deaths in Tokyo was 14.
The CFR for Tokyo is 707/90659 (0.78%). Because there are many young people, the mortality rate may be lower than the average for Japan.
If we estimate the number of infected people in Tokyo to be 70, based on the results of antibody tests, the IFR is 707/700000, or 0.1%.

Table 1: Death statistics as of January 2021, 1 (in order of most deaths per 21 population)

Source: Science Immunological characteristics govern the transition of COVID-19 to endemicity
https://science.sciencemag.org/content/early/2021/01/11/science.abe6522.full

[8] Why we need a vaccine now

Being infected does not immediately confer lifelong immunity.
So now we need a vaccine for lifelong immunity.

The new coronavirus infection has raged in the state of Manaus in Brazil.
When researchers looked at the antibody positivity rate of blood samples, they found that 6% were positive at the end of June and 66% were positive by October, meaning that three in four people in the population had already been infected with the new coronavirus.

The left vertical axis of the solid line graph in Figure A below shows the antibody positivity rate (0-100%), the horizontal axis shows time (February 2020 to November 2), and the right vertical axis shows the daily number of deaths per 2020 people.
Please note that the figures above are not total deaths per 10 population.

The next graph, Figure B, shows the daily number of new deaths per 10 people in each country (UK, US, Brazil, and Japan).
In A, the antibody positivity rate first rose sharply from around May, and from July to November (between the red circles) the antibody positivity rate rose to 5%.
It turns out that most people are infected.

The number of new deaths per day during that period appears to have been 10 per 0.3 people, as shown by the small bar graph for the period indicated by the arrow.
This remains unchanged from the number of new deaths per 10 people recorded for the same period across Brazil (graph B).
This means that even if a large proportion of the population becomes infected, deaths from infection are not likely to decrease significantly, and herd immunity is unlikely to be achieved anytime soon.

In fact, when we look at the antibody-positive patients at our clinic, many have quite low antibody titers, and we think it is not surprising that such people could be reinfected; genetic mutations of the coronavirus may also have an additional impact.

At the very least, it appears that an effective vaccine will still be needed, possibly with multiple doses.

Figure 10: Estimated SARS-CoV-2 antibody prevalence in Manaus, Brazil

Figure 11: New COVID-10 deaths per 1 people per day

Source: Both of the following papers are from Science
Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic.
LF Buss et al., Science 371, 288 (2021). *Includes Graph 3
https://science.sciencemag.org/content/371/6526/288
Herd immunity by infection is not an option
https://science.sciencemag.org/content/371/6526/230.full

*Graph 4
https://www.ft.com/content/a2901ce8-5eb7-4633-b89c-cbdf5b386938

[9] Effectiveness of vaccination: Israeli infections fall after more than two weeks of vaccination

This is the case of Israel, which is the world leader in vaccination.

In Israel, where the coronavirus vaccination drive is progressing at the fastest pace in the world, it was reported on the 12th that the number of infections is lower among people who have been vaccinated more than two weeks ago compared to those who have been vaccinated less than two weeks ago.

Vaccinations began in Israel late last month, and according to local media, more than 1.88 million people, or more than 20% of the population, have received their first dose so far.
Meanwhile, the Ministry of Health announced provisional figures regarding vaccination on the 12th.
Among those who were confirmed to be infected within seven days of receiving the vaccine, 4,484 were infected, and within 8 to 14 days, 3,186 were infected. However, among those who had been infected between 15 and 22 days ago, the number of infected people was 353.
In addition, 375 people were hospitalized after receiving the vaccine, and seven of them had been vaccinated more than two weeks ago.

In other words, the vaccine's effectiveness can be seen two weeks after vaccination, which is roughly the same as the results previously submitted to the FDA by Pfizer and others.
Regarding side effects, in addition to headache and fever, 14 cases of facial nerve paralysis and five cases of convulsions have been reported.

Source: Yahoo! News "Israel's infection numbers fall after more than two weeks of vaccination" Nippon Television Network (NNN) 1/13 (Wed)
https://news.yahoo.co.jp/articles/371c1c1e6b99b87466c73bddc981f408169df753

[2021] Global vaccination rates (January 1, 20)

The numbers in the bar graphs show the vaccination rates. Israel and the Middle East are at the top.

Figure 12: Global vaccination status

Source: FINACIAL TIMES Covid-19 vaccine tracker: the global race to vaccinatehttps://ig.ft.com/coronavirus-vaccine-tracker/

[11] Side effects of the Moderna and Pfizer vaccines

1) Moderna vaccine

Between December 2020, 12 and January 21, 2021, 1 people in the United States were vaccinated with the first dose of the Moderna vaccine. Ten people experienced anaphylactic shock, nine of which occurred within 10 minutes. No deaths were attributed to anaphylactic shock. There were 4,041,396 cases of acute symptoms other than anaphylaxis.

Table 2: Characteristics of reported cases of anaphylaxis after receiving the first dose of the Moderna vaccine

Table 3: Characteristics of patients who reported anaphylactic and non-anaphylactic reactions after receiving the first dose of the Moderna vaccine

Source: https://www.cdc.gov/mmwr/volumes/70/wr/mm7004e1.htm

2) Pfizer vaccine

Between December 2020 and December 12, 14, 12 people received the first dose of the Pfizer vaccine. Twenty-one people experienced anaphylactic symptoms, four of whom were hospitalized and 23 were treated in the emergency room. There were no deaths. Nineteen of the cases were women.

Figure 13: Characteristics of anaphylaxis cases following the Pfizer vaccine

Source: JAMA Insights Clinical Update
January 21, 2021
Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine
https://jamanetwork.com/journals/jama/fullarticle/2775646?
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