Vol.24 (2021/01/20) Positive antibody test rate at our clinic / Infection trends and vaccination rates in Japan and the world / Summary of Omicron strain (incubation period, isolation period, treatment drug) and more

[1] Positive rate of COVID-19 antibody tests at our clinic

We check the positivity rate of new infectious antibodies every month during Health Screening and outpatient clinics, and the results are as follows.
● 2021/09/15-2021/10/14 Number of tests: 282 Number of positive cases: 39 Positive rate (%): 13.8
● 2021/10/15-2021/11/14 Number of tests: 158 Number of positive cases: 16 Positive rate (%): 10.1
● 2021/11/15-2021/12/14 Number of tests: 140 Number of positive cases: 15 Positive rate (%): 10.7
● 2021/12/15-2022/01/14 Number of tests: 147 Number of positive cases: 19 Positive rate (%): 12.9
Even before the Omicron strain became prevalent, when the number of coronavirus patients was low, the positive rate for infection antibodies was around 10%.

Figure 1: Positive rate of antibody tests at Tokyo Midtown Clinic

This shows the changes in coronavirus neutralizing antibodies over time, compiled mainly by Dr. Sakaino of our hospital.
Our hospital uses Abbott antibody tests, and the target neutralizing antibody level two weeks after the second dose of the vaccine is 2 AU or higher. However, based on our experience, we feel that breakthrough infection becomes more likely to occur when the level drops to around 4000 AU.

Figure 2: Changes in neutralizing antibodies over time at Tokyo Midtown Clinic

[Legend]
Vertical axis: The rate of decrease (%) in neutralizing antibody values ​​from the second blood draw onward, assuming the neutralizing antibody value at the first blood draw is 1%
Horizontal axis: Number of days since the first neutralizing antibody blood collection (Day 1)

When coronavirus-neutralizing antibodies are tested for more than twice through blood tests, the antibody titer appears to decrease to 2-1% about three months after the first test, with some variation from person to person.
People with antibody titers higher than this may have a history of COVID-19 infection.
Based on the above, it is thought that the period when coronavirus antibodies remain at or above 500 AU is up to approximately six months after receiving two doses of the vaccine.

[2] Infection status in Japan

The sixth wave is coming due to the Omicron strain.
The number of infected people has increased sharply since January, exceeding 1 per day.
However, the number of serious cases is still low as of January 1th.

Figure 3: Number of new infections and serious cases in Japan (as of January 2022, 1)

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

[3] Global situation

To understand the global infection situation, it is best to first understand the vaccination situation.

(Source: up to Figure 15) Financial Times Coronavirus chart: see how your country compares | Free to read | Financial Times (ft.com)
https://ig.ft.com/coronavirus-chart

First of all, the countries with the most advanced vaccinations are:

Figure 4: Countries with the highest vaccination rates (1st to 9th)

In countries like Denmark, Singapore and South Korea, 2-80% of people have received two doses of the vaccine, and nearly 85% have received a third booster dose.
Next come the UK, Italy, France and other countries, where over 2-70% of people have received two doses, and 75-3% have received the third dose.

Figure 5: Countries with the highest vaccination rates (10st to 24th)

In Japan, the two-dose vaccination rate is nearly 2%, but it is not particularly high compared to other countries. The three-dose vaccination rate is very low compared to other countries, at only 80%.

Figure 6: Countries with the highest vaccination rates (49st to 53th)

The United States has a lower two-dose vaccination rate of 2% compared to other countries, and the three-dose vaccination rate is 62%.

Figure 7: Countries with the highest vaccination rates (54st to 57th)

With this situation in mind, let's look at graphs of the number of new cases and deaths.
First, let's compare the number of new cases and deaths in the United States, the United Kingdom, the EU, and Japan.

Figure 8: Comparison of new infection numbers (US, UK, EU, Japan)

We can see that the sixth wave of the Omicron strain has a much larger number of patients than in the fall of 6. The UK and the US appear to have passed their peak.

Figure 9: Comparison of new deaths (US, UK, EU, Japan)

In terms of deaths, the US also had a peak in the fall of 2021. The number of deaths in the UK is increasing. The peak of the number of deaths in the EU seems to have passed, but the impact of Omicron is yet to come. Compared to these countries, Japan seems to have far fewer deaths.
We won't know for sure until we see future developments, but the low number of patients in Japan does not necessarily appear to be due solely to differences in vaccination rates.
Now let's compare it with Asia.

Figure 10: Comparison of new infection numbers (Japan, South Korea, Singapore, Thailand, and Taiwan)

The number of new patients was high in Singapore and Thailand in the fall of 2021, and in South Korea in December 2021. These are likely due to the Delta strain. It is likely that the resurgence in Japan, Singapore, and Thailand from January 12 is due to the Omicron strain.

Figure 11: Comparison of new deaths (Japan, South Korea, Singapore, Thailand, and Taiwan)

Looking at the number of deaths, we can see that Thailand and Singapore had many deaths in the fall of 2021. We can see that the number of deaths in South Korea was high in December 2021. Since November 12, the number of deaths has been very low in Japan and Taiwan.
So what about India, which previously experienced a major peak, and South Africa, where the Omicron strain was found?

Figure 12: Comparison of new infection numbers (Japan, United States, United Kingdom, South Africa, India)

Comparing with the pattern in Japan, we can see that new cases in India have been almost completely suppressed since June last year. South Africa will see a peak in December 27, which is due to the Omicron strain. The two-dose vaccination completion rate in South Africa is 1%, and even if the vaccination rate is low, the peak of Omicron infections may pass in about a month.

Figure 13: Comparison of new deaths (Japan, United States, United Kingdom, South Africa, India)

Looking at the death toll in South Africa, it looks like there is a possibility that it will be one month behind new infections.
Let's look at the situation in advanced vaccination countries: Israel, Denmark, Chile, the UAE and Singapore.

Figure 14: Comparison of new infections (United States, Israel, Denmark, UAE, Singapore, Chile)

The situation is quite different even in advanced vaccine-producing countries. The number of new cases in Denmark and Israel is increasing rapidly, likely due to the influence of the Omicron strain. However, new cases have been suppressed in Chile, the UAE, and Singapore. There may be differences in infection control measures themselves, or racial differences.

Figure 15: Comparison of new deaths (USA, Israel, Denmark, UAE, Singapore, Chile)

In terms of deaths, Denmark has a high number, while Israel and Chile have significantly lower numbers.
The UAE and Singapore are at significantly lower levels than Chile.

Based on these findings, although the rate of infection with the Omicron strain is quite high even in countries where three doses of the vaccine have been administered, it is possible that this is due to factors such as infection control measures and racial differences.
Regarding future vaccinations, there is talk of a fourth vaccination, as in Israel, but I think it will take another 4-1 years to develop a combination of multiple vaccines tailored to the new coronavirus variant. If variants with a low rate of severe symptoms continue to appear in the future and we continue to take normal infection control measures, I hope that we will soon be able to take a similar approach to influenza.

[4] Summary of the Omicron strain

The Omicron strain is quite distinct from the other Delta strains in its evolutionary lineage.

Figure 16: New coronavirus family tree

Source: SCIENCE Where did 'weird' Omicron come from?
https://www.science.org/content/article/where-did-weird-omicron-come

Figure 17

Although the Omicron strain has a lower risk of hospitalization, the number of infected individuals is so high that hospitalizations, serious illness, and deaths are increasing dramatically, placing a heavy strain on the healthcare system.

The third vaccination is expected to be effective in preventing infection.

Figure 18

Furthermore, it seems that it may be effective in preventing the disease from becoming severe.

Figure 19

Figure 20

Comment from Professor Atsuro Hamada of Tokyo Medical University
"There is data that suggests the risk of developing severe symptoms with the Omicron strain is about one-third that of the Delta strain, but as the number of infected people increases, the number of people who become seriously ill will also increase. Currently, most infected people are young people, but if the virus spreads to elderly people, they may become more susceptible to serious symptoms. Even if the risk of developing severe symptoms is low, it remains a situation in which caution is needed."

"The Omicron strain is said to easily attach to the upper respiratory tract, such as the nose and throat, and multiply there. For that reason, the virus is easily dispersed into the surrounding area when sneezing or coughing, which is thought to make it more contagious. With the Delta strain, there were cases of people who were having a barbecue outdoors becoming infected, but the Omicron strain is more contagious, so I would like people to be more careful than ever. Please continue to take precautions such as wearing masks, washing your hands, and avoiding crowded places, and when you are able to receive a booster vaccination, please get it."

Source: NHK News "More than 1 people infected with COVID-2022: What we know about the Omicron strain" (January 1, 12)
https://www3.nhk.or.jp/news/html/20220112/k10013426651000.html

[5] Incubation period of the Omicron strain and quarantine period for infected individuals and close contacts

Because the incubation period is short, it is possible to quickly determine whether or not someone has been infected. Considering the duration of viral shedding, this should be shortened by at least two days compared to conventional strains.

Figure 21

Source: Sankei Shimbun, "Omicron: National Institute of Infectious Diseases considers shortening waiting period for close contacts: 'Incubation period of around three days'" (January 2022, 1)
http://a.msn.com/01/ja-jp/AASH9Js?ocid=se

Regarding the isolation periods for infected individuals and close contacts, we would like to introduce an article by Kurahara Masaru of the National Hospital Organization Kinki Central Respiratory Center.

Source: (Figures 22 and 23) Yahoo! News "Summary of the current state of quarantine periods for those who test positive for COVID-2021 and those in close contact with them: Other countries are moving towards shortening the period" (December 12, 29)
https://news.yahoo.co.jp/byline/kuraharayu/20211229-00274875

The process for releasing positive patients from treatment will be the same as before.

Figure 22

Those who have had close contact with a patient are required to undergo a health observation (home quarantine) period. The day of last contact with the patient during the infectious period is counted as day 0, and the period begins the next day as "14 days." If there is a family member who has tested positive, this can reach a maximum of "10 days" (14 days + 24 days). This is an extremely long period, and has a huge impact on society.

Figure 23

Due to the home quarantine of close contacts as mentioned above, a shortage of medical staff and essential workers has become an issue. Therefore, on January 1th, the following changes were made:

Figure 24

In addition to medical workers, "essential workers" who support society and daily life, such as police, firefighters, public transportation, and nursing and childcare workers, will be released from standby if they test negative consecutively in a PCR test or quantitative antigen test conducted on the sixth day after their last contact with an infected person, or in a qualitative antigen test conducted on the sixth and seventh days, at the discretion of the local government.

Source: NHK News "Maintaining social functions" - Shortening waiting period for close contacts (January 2022, 1)
https://www3.nhk.or.jp/news/html/20220114/k10013430341000.html

On January 1, the Ministry of Health, Labor and Welfare notified local governments across the country that medical workers who have come into close contact with a person infected with the new coronavirus will be allowed to continue working, provided they have received two doses of the vaccine and test negative every day.

https://www.mhlw.go.jp/content/000879698.pdf

[Requirements]

- The person is a medical professional who is difficult to replace by other medical professionals.
- You have received two doses of the COVID-14 vaccine and have had close contact with a COVID-XNUMX patient XNUMX days after the second dose and have been identified as a close contact.
- You are asymptomatic and have tested negative using a nucleic acid detection test or quantitative antigen test (or, if unavoidable, a qualitative antigen test kit) before work every day.
- The manager of the medical staff member in question understands the duties of the medical staff member who is a close contact.

[6] Quarantine period for infected persons and close contacts abroad

On December 2021, 12, the US Centers for Disease Control and Prevention (CDC) issued a recommendation to shorten the isolation and home quarantine period for those who test positive for COVID-27 and those who have had close contact with them to five days.

The amendment of January 2022, 1 changed the condition to require additional vaccinations.

Source: US CDC Quarantine and Isolation Updated Jan. 9, 2022
https://www.cdc.gov/coronavirus/2019-ncov/your-health/quarantine-isolation.html

(Table 1)

*The date of infection or the date of contact with an infected person is counted as day 0. The following day is counted as day 1.

Figure 25

As mentioned above, there seems to be a trend to exempt infected people from home quarantine after five days.

Source: Sankei Shimbun, "Self-isolation periods shortened in Europe, increasing number of people out of work, concerns over economic paralysis" (2022/1/13)
https://www.sankei.com/article/20220113-2JRB2XE2ANJGHAXL2JVE25M2MA/

[7] How far will the infection spread?

The Omicron strain is the predominant strain causing infections around the world.

Regarding the Omicron strain of the new coronavirus, the World Health Organization (WHO) has once again called on countries to accelerate vaccinations, saying that there is a risk that more than half of the population in Europe, Central Asia, and other regions will be infected within the next six to eight weeks.

At a press conference on the 11th, WHO Regional Office for Europe Director-General Martin Luther King said the Omicron strain of the mutated virus is highly contagious and has already become the mainstream of infections, especially in Western European countries.

The Omicron strain is also becoming more prevalent in the Balkan countries.
Director-General Kluge then expressed strong concern about the 53 countries in Europe, Russia and Central Asia covered by the WHO Regional Office for Europe, saying, "Over the next six to eight weeks, more than half the population is at risk of being infected with the Omicron strain."

On the other hand, Director-General Kluge reiterated his call for countries to accelerate vaccination, saying that being vaccinated can reduce the risk of severe illness or death if infected with the Omicron strain.

Source: NHK News "WHO: Over half of Europe and Central Asia's population may be infected in 6 to 8 weeks" (January 2022, 1)
https://www3.nhk.or.jp/news/html/20220112/k10013425871000.html?utm_int=detail_contents_news-related_008

Next, I would like to introduce a somewhat optimistic article about when Omicron will converge.

A study reported in the International Journal of Infectious Diseases by researchers at Steve Biko Academic Hospital in South Africa compared 466 infected patients who were hospitalized after mid-November last year with 3,976 patients who were hospitalized before that, and found that the mortality rate, which was 21.3% before, was 4.5% during the surge in Omicron. The length of hospitalization was also halved, as patients infected with the Omicron strain were discharged after an average of four days, while those infected with other mutant strains took 8.8 days.
If this pattern is replicated globally, it could signal that the current pandemic is entering an endemic phase.

Meanwhile, a Pfizer executive said in December that he expects the pandemic to continue for the next one to two years and become endemic in 2024.

Dr. Kunio Yano, special adviser on infectious disease management at Hamamatsu Medical Center, said, "Based on research in South Africa and the UK, it is almost certain that the rate of severe symptoms will decrease. The incubation period was also around 5.5 days when it first emerged in Wuhan, China, and 4-5 days for Delta, but Omicron is 3-3.5 days, which is quite close to the coronavirus that causes the common cold. It is possible that it will become the 'fifth' cold virus that we have now, after Omicron or the next mutant strain." "The number of Omicron strain infections will peak around February, but we will not see as many severe cases as in the fifth wave, and the virus will likely subside around March. A wave of mutant strains that are more infectious, have a short incubation period, and are less likely to cause severe symptoms will occur around June to July, but this may subside if certain conditions are met, such as the expansion of the third vaccination of the vaccine and approval of oral medication. It is not surprising that a debate will emerge this summer about the pros and cons of wearing masks."

Source: Yahoo! News "Pandemic may end in Omicron, number of infections overseas peaks in one month"
https://news.yahoo.co.jp/articles/fe3c3029d3e9cfb971a60045232ef07dbb190787

[8] Regarding COVID-19 treatment drugs

On December 12th of last year, the first oral antiviral drug for COVID-24 in Japan was given special approval, and expectations for the treatment are high.

Figure 26: Oral antiviral drugs for COVID-XNUMX currently under development in Japan

Figure 27: Drugs for treating COVID-XNUMX in Japan

(Created by the Medical Tribune editorial team based on the Japanese Association of Infectious Diseases' "Considerations for Drug Treatment of COVID-19, 11th Edition")

・Antibody cocktail therapy casirivimab/imdevimab: In principle, it must be administered within seven days of the onset of symptoms, and its effectiveness decreases if treatment is delayed. By making it available for use in outpatient treatment, its prescription spread rapidly and contributed greatly to preventing the disease from becoming severe. Without this drug, medical care during the fifth wave would have been even more strained.

Molnupiravir (Merck: LaGebrio) is a synthetic nucleoside derivative, the same as the antiviral drug remdesivir for COVID-19. It was approved in the UK on November 11 last year. When SARS-CoV-4 enters human cells and begins replicating, molnupiravir slips into the viral RNA, causing errors in the viral RNA, preventing replication and exerting its antiviral effect.

・Paxlovid (Pfizer: Paxlovid) was granted emergency use authorization by the EMA on December 12th last year, and by the US Food and Drug Administration (FDA) on the 16nd of the same month. It is taken orally in combination with nirmatrelvir, a 22CL protease inhibitor, and low-dose ritonavir. The antiviral drug nirmatrelvir inhibits the activity of SARS-CoV-3 2CL protease, an enzyme necessary for SARS-CoV-2 self-replication, suppressing viral proliferation. Ritonavir is a classic protease inhibitor for HIV, but is often used as a booster drug for other protease inhibitors. Ritonavir suppresses the metabolism of nirmatrelvir, maintaining high blood levels.

Both molnupiravir and paxlovid require treatment to begin within 5 days of onset.

- There is a large difference in the effectiveness of reducing the risk of hospitalization and death, with molnupiravir at 30% and paxlovid at 89%.

Molnupiravir is not recommended for pregnant or breastfeeding women. Women of childbearing potential should use contraception while taking the drug and for 4 days after.

Paxlovid is used in combination with the antiviral drug nirmatrelvir and ritonavir, which enhances its effectiveness. Ritonavir has a strong affinity with the hepatic drug-metabolizing enzyme CYP3A, and can competitively inhibit the metabolism of other drugs (especially those metabolized by CYP3A), increasing their blood concentrations, so caution is required. CYP3A is involved in the metabolism of many medicines, and when used in combination with statins for hyperlipidemia treatment, calcium antagonists, the anticoagulant warfarin, and the immunosuppressant tacrolimus, for example, there is a risk of interactions causing an increase in blood concentrations.

Source: Medical Tribune, "How will the advent of oral medications change COVID-2022 treatment? Great progress in treatment, but many challenges remain" (January 1, 7)
https://medical-tribune.co.jp/rensai/2022/0107543087/