Vol.19 (March 2021, 03) Antibody-positive patients at our clinic / Latest trends in Japan and the world / Global infection status of mutant viruses / Vaccination status / Vaccine side effects / Vaccine effectiveness, etc.

[1] Antibody positivity rate

From January 2021 to February 1, 15, 2 out of 14 people (306%) tested positive for COVID-13 antibodies.
As expected, the number is still on the higher side.

Figure 1: Positive antibody test rate at our clinic

Incidentally, the Ministry of Health, Labour and Welfare reported that the antibody positivity rate among the general public who agreed to participate in a survey conducted from December 12th to 14th (25 people in Tokyo) was 3,399%. However, this only includes people who tested positive for both types of antibody tests; if we calculate only the positivity rate for the antibody test made by Roche, the same company that uses our clinic, the result is 0.91%.
The difference between the two figures from our hospital and the Ministry of Health, Labor and Welfare may be due to a sudden increase in the number of infected people since the end of the year, or there may be bias due to differences in the age distribution of those who agreed to the survey and their willingness to protect themselves from infection.

[2] The latest situation in the world and Japan

According to the New York Times, the number of new cases worldwide is declining.

Figure 2: Number of new infections worldwide (as of March 2021, 3)

It seems that the number of cases in Brazil is increasing due to a mutated virus.

Figure 3: Number of new infections in Brazil (as of March 2021, 3)

Source: The New York Times “Coronavirus World Map: Tracking the Global Outbreak”
https://www.nytimes.com/interactive/2020/world/coronavirus-maps.html

The number of new infections in Japan is decreasing, but as reported, caution is still required.

Figure 4: Number of new infections in Japan and number of people requiring hospitalization or other treatment (as of March 2021, 3)

Source: Ministry of Health, Labor and Welfare, "About the new coronavirus infection: Domestic outbreak status, etc."
https://www.mhlw.go.jp/stf/covid-19/kokunainohasseijoukyou.html#h2_1

[3] Global infection status of mutant viruses

Darker colors indicate the spread of the mutant virus within the country, while lighter colors indicate the detection of the mutant virus in travelers.

1) B.1.1.7. type (VOC-202012/01): Discovered in the UK, it is said to be 30-50% more contagious.
It is also starting to spread within Japan.

2) B.1.351 (501Y.V2): Found in South Africa, this variant may be less effective against current vaccines.
It doesn't seem to have spread in Japan yet.

3) B.1.1.28 (501Y.V3): This is the Brazilian type. It was first detected in Japan when travelers to Brazil were checked. This may also be less effective against current vaccines.

Source: The New York Times “Coronavirus Variants and Mutations”
https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html

Source: National Institute of Infectious Diseases, March 2021, 3, "Cases of new variants of the novel coronavirus in Japan, raising concerns about increased infection and transmissibility and changes in antigenicity (as of February 9, 2021)"
https://www.niid.go.jp/niid/ja/diseases/ka/corona-virus/2019-ncov/10221-covid19-37.html

On the 8th, Saitama Prefecture announced that 10 men and women aged between under 70 and their 20s living in the prefecture have been confirmed to be infected with the mutated new coronavirus (501Y.V3) that is spreading in Brazil.

Source: NHK News March 2021, 3, 8:21 p.m. "05 new cases of mutant virus confirmed in Saitama Prefecture"
https://www3.nhk.or.jp/news/html/20210308/k10012904591000.html

The virus mutates very rapidly, and when it was discovered in Wuhan in December 2019, there were already reported to be 12 different strains of the virus.

An investigation by a World Health Organization (WHO) team that traveled to Wuhan, Hubei Province, China to investigate the source of the new coronavirus has found signs that the infection in Wuhan, which was confirmed in December 2019, was much more widespread than previously thought.
For the first time, the team found that more than 12 different strains of the virus were already present in Wuhan as of December 2019.
This has further fuelled concerns that the new coronavirus may have been spreading within China long before it was first officially identified in mid-December.
The investigation was conducted after receiving information from a team of Chinese experts about 174 cases confirmed in Wuhan and surrounding areas in December 2019. The 174 cases were likely to have been serious, and the investigation team estimated that, given this large number, more than 1,000 people may have been infected in Wuhan as of December.

Source: CNN News, February 2021, 2, "Wuhan's COVID-15 outbreak may have been larger than expected, WHO investigation team, CNN EXCLUSIVE"
https://www.cnn.co.jp/world/35166483.html

[4] Vaccination status

Israel has reached 90% of the population. Japan is lagging far behind.

Figure 5: Vaccination rates (Comparison between the UK, Israel, US, EU, Japan and Singapore)

Source: FINANCIAL TIMES “Covid-19 vaccine tracker: the global race to vaccinate” https://ig.ft.com/coronavirus-vaccine-tracker/?
areas=gbr&areas=isr&areas=usa&areas=eue&areas=jpn&areas=sgp&cumulative=1&populationAdjusted=1

[5] Vaccine side effects

The Japanese Society of Infectious Diseases recently published recommendations touch on the side effects of vaccines.
It is said that people with a history of allergies should be careful, but we will look at how many people experience side effects and what kind of side effects they have.

The Japanese Association of Infectious Diseases has formulated the "Recommendations for COVID-19 Vaccines (2nd Edition)" (hereinafter referred to as the 2nd Edition) and released it on February 2th. Based on the domestic and international information to date, the report states that "the effectiveness of the messenger RNA (mRNA) vaccines from Pfizer and Moderna, which are being administered overseas, is high, side effects are limited to transient reactions, and no serious health damage has been observed other than anaphylaxis." On the other hand, a US survey reported that the incidence of anaphylaxis with both vaccines combined was 26 times per million vaccinations. 100% of the cases were women, and the report clearly stated that "particular caution is required in those with a history of allergies to medicines or cosmetics." Although there are some unknowns regarding the long-term effectiveness and safety of the vaccine, the report emphasized that "it is desirable to receive the novel coronavirus (SARS-CoV-4.5) vaccine approved in Japan in order to put an end to COVID-94.5."

The report stated that the number of people over 75 years old who were evaluated in clinical trials was insufficient, and that this was an issue for future consideration. In addition, the rate of people with underlying diseases was only in the 20% range in all clinical trials for the vaccines, and the report stated that "the evaluation is insufficient and further consideration is necessary."

An analysis of the reports of anaphylaxis showed that 94.5% were women, and 38.7% had a history of anaphylaxis. In terms of when it occurred, 15% occurred within 77.4 minutes and 30% occurred within 87.1 minutes after vaccination. The majority of symptoms involved skin and respiratory symptoms, and only one case involved a drop in blood pressure that suggested anaphylactic shock.

Serious side effects occurred in 9.2% of cases, most frequently after the second dose
The most common side effects were headache (22.4%), fatigue (16.5%), dizziness (16.5%), chills (14.9%), and nausea (14.8%). Severe side effects were seen in 9.2% of cases, and deaths were reported in 1.6% of cases. Most deaths occurred among those receiving the vaccine in elderly care facilities, but no clear connection to the vaccine was found in any of the cases. Side effects are more frequent after the second dose.

Source: Medical Tribune Medical News, March 2021, 03, 01:18 "No new serious side effects from coronavirus vaccine, Japanese Association of Infectious Diseases recommends"
https://medical-tribune.co.jp/news/2021/0301535470/index.html

Figure 6: How many people experience side effects from the COVID-XNUMX vaccine?

Source: NHK News broadcast on February 2021, 2, "What are the symptoms of side effects from the COVID-22 vaccine?"
https://www3.nhk.or.jp/news/html/20210222/k10012880101000.html

[6] Precautions regarding vaccination methods

Measures to deal with side effects after vaccination, as well as precautions regarding vaccinations, are becoming more detailed as vaccination data accumulates.

The US Centers for Disease Control and Prevention (CDC) has published clinical recommendations and precautions regarding the use of mRNA vaccines for COVID-19 on its website, which is updated as needed (last updated on February 2).

Post-vaccination reactions
All recipients should be observed for 15 minutes after vaccination. Anyone with a history of any immediate allergic reaction or anaphylaxis to a vaccine or injection should be observed for 30 minutes after vaccination.

Reactogenicity after vaccination can include local reactions (pain, swelling, erythema at the injection site, and axillary lymphadenopathy in the arm where the vaccine was administered) and systemic reactions (fever, fatigue, headache, chills, muscle and joint pain). Among people who received an mRNA COVID-19 vaccine, 80% to 89% had at least one local reaction, and 1% to 55% experienced a systemic reaction.

Most systemic reactions are mild to moderate, occur within 3 days after vaccination, and resolve within 1-3 days. These symptoms occur more frequently in younger people than in older people (those 55 years and older for the Pfizer vaccine and 65 years and older for the Moderna vaccine), and are more frequent and severe after the second dose. Even if you experience local or systemic reactions after the first dose, we recommend that you receive the second dose of the vaccine unless you have a contraindication to vaccination in order to fully utilize the vaccine's preventive effect against COVID-2.

Antipyretics or analgesics (e.g., acetaminophen or nonsteroidal anti-inflammatory drugs [NSAIDs]) can be used to treat local or systemic reactions after vaccination.
The agency also does not recommend administering antihistamines before vaccination to prevent allergic reactions.

Vaccination is also recommended for people with a history of COVID-19.
(Somewhat)
Those who experience only delayed local reactions at the injection site (e.g., erythema, induration, pruritus) after the first vaccination do not meet any contraindications or precautions for receiving the second vaccination. It is not known whether those who experience local reactions after the first vaccination will experience similar reactions after the second vaccination, but this is not thought to pose a risk of anaphylaxis after the second vaccination.

Although data is limited, patients with immunocompromises, autoimmune diseases, Guillain-Barré syndrome, and Bell's palsy can still be vaccinated.
There is currently little data on the safety of mRNA COVID-19 vaccination for pregnant women, but because the mRNA vaccine is not a live vaccine, it is thought that there is little risk to pregnant women or fetuses. Pregnant women may receive the vaccine if they are included in the groups recommended for vaccination (such as medical workers). However, symptoms similar to those experienced by other people may occur after vaccination, and fever may have a negative impact on the pregnancy. If a pregnant woman develops symptoms such as fever after vaccination, the administration of acetaminophen will be considered.

Source: Nikkei Medical, March 2021, 03, "CDC introduces precautions for receiving mRNA COVID-02 vaccine: What are the reactions to the COVID-19 vaccine after vaccination and how should you deal with them?"
https://medical.nikkeibp.co.jp/leaf/mem/pub/report/t344/202103/569311.html

[7] Vaccine effectiveness

1) Paper on the effectiveness of the Pfizer vaccine in Israel

In Israel, where vaccinations against the new coronavirus (SARS-CoV-2) are progressing at the fastest rate in the world, the efficacy of the mRNA vaccine Tosinamelan, jointly developed by Pfizer and BioNTech, was evaluated based on data from nationwide mass vaccination participants. The vaccine showed 19% efficacy against the onset of COVID-94, which was almost identical to the results of clinical trials, and was published in N Engl J Med (online edition, February 2021, 2).
2020年12月20日～21年2月1日に1回目の接種を受けた16歳以上でSARS-CoV-2感染の既往がない59万6,618例を対象とし、人口統計学的および臨床的特徴をマッチさせたワクチン非接種の対照59万6,618例を選出。1回目接種後14〜20日目、21〜27日目、2回目接種後7日目～経過観察終了日におけるSARS-CoV-2への感染およびCOVID-19発症、入院、重症化および死亡について検討した。

Decline rate

Vaccine efficacy in each period was consistent across all age groups.
"In this study, the efficacy of tosinameran was estimated to be high at 95%, similar to the 94% efficacy obtained in clinical trials. In addition, high efficacy was shown against more serious outcomes such as hospitalization, severe illness, and death associated with COVID-19, and efficacy tended to increase over time. These results suggest that tosinameran may be useful in reducing the serious global impact of the COVID-7 pandemic."
N Engl J Med. 2021 Feb 24. doi: 10.1056/NEJMoa2101765.
BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting

Source: Medical Tribune Medical News March 2021, 03 "Israeli mass coronavirus vaccination 03% effective: Tojinamelan, jointly developed by Pfizer and BioNTech"
https://medical-tribune.co.jp/news/2021/0303535486/

2) A paper has been published on the effectiveness of the Pfizer vaccine (BNT162b2) and the AstraZeneca vaccine (ChAdOx1) after the first dose in Scotland.

In conclusion, the Pfizer vaccine (BNT28b34) reduced COVID-19-related hospitalizations by 162% and the AstraZeneca vaccine (ChAdOx2) reduced them by 85% 1-94 days after the first vaccination. In subjects aged 80 years and older, both vaccines reduced COVID-28-related hospitalizations by 34% 19-81 days after the first vaccination. Even a single dose was highly effective in practice.

Source: Effectiveness of first dose of COVID-19 vaccines against hospital admissions in Scotland:
national prospective cohort study of 5.4 million people
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3789264

3) The AstraZeneca vaccine (ChAdOx1) appears to be more effective if the second dose is administered three months or later.

As shown in the figure below, when the interval between the first and second doses was examined across groups of less than 1 weeks, 2-6 weeks, 6-8 weeks, and more than 9 weeks, both the vaccine effectiveness rate (vertical axis) and the antibody titer after vaccine administration (horizontal axis) increased with increasing interval.
In other words, an interval of 12 weeks (3 months) or more between vaccine doses was most effective.

Figure 7: Relationship between binding and neutralizing antibodies 2 days after the second dose

Source: The Lancet
Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomized trials.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fulltext

[19] People who have already been infected with COVID-XNUMX appear to have a significant increase in antibody titers even with just one dose of the vaccine.

In those who were not infected or whose antibody titers had not increased, the antibody titers increased to about 2X two weeks after the first vaccination, but in asymptomatic and symptomatic infected individuals, the antibody titers increased to 1000X from the seventh day.
Therefore, it was thought that a single dose of the vaccine would be sufficient for those who were already infected, even if they were asymptomatic.

Figure 8: Anti-SARS-CoV-2 antibody responses after a single dose of vaccine in healthcare workers

Source: Binding and Neutralization Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2. JAMA. Published online March 1, 2021.
https://jamanetwork.com/journals/jama/fullarticle/2777171

[9] Vaccine passports

There is a push to ease restrictions, including travel, after vaccinations are administered.
Israel has already begun issuing vaccine passports to people who have received their second dose, allowing holders to use cinemas and hotels, as well as travel freely within the country and abroad.

Major IT companies have begun development
1) Digital Health Pass: IBM and Salesforce
https://www.ibm.com/products/digital-health-pass

2) Vaccination Credential Initiative: Microsoft, Salesforce and Oracle, as well as US health care non-profit Mayo Clinic
https://www.cnbc.com/2021/01/14/microsoft-salesforce-and-oracle-working-on-covid-vaccination-passport.html

3) The Commons Project: The World Economic Forum, Rockefeller Foundation.
https://thecommonsproject.org/

4) Google and Apple

5) Digital Green Pass: The European Union

It also appears that the airline industry is already testing the introduction of Travel Pass.

The International Air Transport Association (IATA) said it plans to launch a digital Covid Travel Pass "within weeks".
The app, available for both iOS and Android, will be free for passengers, IATA said.
Singapore Airlines was the first airline to begin testing the service in December, and it is being considered by most airlines in the Asia-Pacific region.
According to IATA, paper certificates are considered to be too risky. Fraudulent practices such as selling negative test certificates at airports have already been uncovered in France and Malaysia, so electronic certificates are considered important.

Figure 9: IATA Travel Pass Participating Airlines

Source: BBC News, February 2021, 2, "Covid: Airline industry travel pass ready 'within weeks'"
https://www.bbc.com/news/business-56165563
IATA Website "IATA Travel Pass Initiative"
https://www.iata.org/en/programs/passenger/travel-pass/