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August2022

Volume 9

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N 24
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Editorial
Harm of vaccine and Harm of data manipulation
Adverse Reactions
Vaccine increases myocarditis mortality
Review
Evidence for healthy vaccinee effect

CONTENTS（August 2022, Vol. 9, No. 24）
Editorial
Harm of vaccine and Harm of data manipulation

18

Adverse Reactions
Vaccine increases myocarditis mortality
News
Imbalance in baseline characteristics in molnupiravir trials
Review
Evidence for healthy vaccinee effect(1) Lower rate of non-covid death in vaccinated(2) Lower COVID-19 incidence at the day of inoculation

19
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24
34

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ED

HECK

Editorial

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Harm of vaccine and Harm of data manipulation

Translated from the Editorial in Med Check(in Japanese) Jul. 2022 ; 22 (102)：79

Recently, two cases of data manipulation by the Japanese Ministry of Health, Labor and Welfare(MHLW) have been revealed in relation to SARS-CoV-2 vaccines.

One is the case of misregistration of vaccine recipients. When comparing the proportion of newly
reported COVID-19 patients by vaccination status, patients who were surely vaccinated but withunknown date of vaccination were treated as “non-vaccinated” by MHLW. Hence, the proportion was
extremely low in the vaccinated and extremely high in the unvaccinated. As a result, the data gave theimpression that the vaccine worked very well.
The data from April 11 onwards have been corrected as pointed out by a researcher. As a result, theproportion of new infections per 100,000 people no longer differs across most age groups. Considering

Editorial

the “healthy vaccinee effect”, the protective effect of vaccine is even lower.

The other is the manipulation to make the proportion of patients with myocarditis after vaccination
appear low, as reported by a local TV. It is problematic because it is used in a promotion flyer of the
MHLW, which local governments use for publicity, to show that the vaccine is safe.

The flyer showsthat the proportion of persons with myocarditis among vaccinated males in their 20s was 10 per million(Pfizer) and 26 per million (Moderna), while the proportion among COVID-19 male patients aged 15 to

39 was 834 per million. The head of the MHLW's Health Bureau told the Diet that the latter proportionwas calculated from the following data: as of May 31, 2021, among 4,798 hospitalized COVID-19
patients of the same age in the hospitals nationwide, 4 had myocarditis. However, by this time, thecumulative number of male COVID-19 patients aged 15 to 39 was about 160,000. Four patients withmyocarditis among 160,000 people means that proportion is as low as 25 per million.

The proportion among the vaccinated above is too low according to the data from the National
Institute of Infectious Diseases. It is 102 per million in their teens and 47 in their 20s after two doses ofModerna’s vaccine. This proportion is much higher than that in patients with COVID-19. If you don't

receive the vaccine nor have COVID-19, the incidence of myocarditis is even lower. Even after thesewere pointed out, the MHLW has no plan to change the description in the flyer.

The data manipulation of MHLW is nothing new. Therefore, MHLW cannot be expected to criticallyexamine and review the data manipulation of mornupiravir, the manipulation of important baseline risk
factors and the suspected masking failure of SGLT2 inhibitors’ trials. We recognize again that the roleof this bulletin will become more and more important.

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Adverse Reactions
SARS-CoV-2 Vaccination Information
Increased myocarditis mortality especially in
20s to 30s adults
Translated and revised from Med Check (in Japanese) May 2022 ; 22 (101):70-72
Med Check Editorial Team

Abstract●Japan’s Ministry of Health, Labour and Welfare (MHLW) announced that cases of myocarditis after SARS-COV-2
vaccination had been confirmed and added warning to the package insert. In other countries, the association
between myocarditis and SARS-COV-2 vaccination has been reported mainly in young males. In this article, we
analyzed the association between myocarditis death and SARS-COV-2 vaccination based on the disclosed data.
●Myocarditis mortality after vaccination increased significantly as compared with that in the reference
population (2019 population); particularly, it was about 21-fold and 14-fold ㏌ 20s and 30s adults, respectively.
When suspected cases were included, it was 35-fold and 16-fold, respectively. In 40s adults, it was alsosignificantly higher: 4.7-fold (5.9-fold when suspected cases were included).
●The post-vaccination myocarditis mortality rate may be higher, due to possible unreported deaths after
vaccination, possible misclassification of cause of death and healthy vaccinee effect.

Conclusion: SARS-COV-2 vaccines are very harmful in 20s to 40s adults.

Keywords:
vital statistics, reporting omission, healthy vaccinee effect, frailty exclusion bias, misclassification, information bias,
person-years

Introduction

to the package insert. The warnings, however only include
that most myocarditis cases improve with rest during

SARS-COV-2 vaccines administration was launched on

hospitalization, and do not mention death cases [4]. Therefore,February 17th, 2021 in Japan, and as of February 2022, more

the association between vaccination and myocarditis death hasthat 80% of the population has reportedly been vaccinated [1].

not been clarified.

Myocarditis is known as one of the adverse reactions to

Myocarditis mortality rate in the vaccinated population

the SARS-COV-2 vaccines in young adults. For example,

was compared with that in the general population in 2019 as

in Israel, many cases of myocarditis were reported in youngreference. In order to examine the impact of under-reporting

males after the second dose [2]. In Korea, a 22-year-oldof post-vaccination deaths and other factors, total mortality

male with no complication suddenly died 5 days after he hadin the post-vaccination population with those in the reference

received Pfizer vaccine. The diagnosis of myocarditis was

population was also compared. In addition, we calculated age

confirmed at autopsy [3].

adjusted total mortality in the vaccinated population in Japan

In Japan, the Ministry of Health, Labour and Welfare(MHLW) announced that cases of myocarditis after SARS-

and non-COVID-19 mortality rate by vaccination status in the
United Kingdom (UK).

COV-2 vaccination had been confirmed and added warnings
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COVID-19 Information
Table 1: Calculation methods of person-years for vaccinated population

column for cause of death on theabove summary list. “Suspectedmyocarditis death case” wasdefined as the case in which
it can be considered that thereporter suspected “myocarditis”
from the description in the “othercolumn” on the above summary
list. They were classified as
death from (or suspected from)I40 (acute myocarditis) under theb: average days from dose 1 to death: 9.62 days
d: average days from dose 2 to death: 32.58 days

10th revision of the International
Statistical Classification of
Diseases and Related Health Problems (ICD-10).

Risk of myocarditis death from SARS-COV-2
vaccines

Period of observation after vaccination:
In Japan, doctors are required to report serious reactions
within 28 days vaccination if they suspected an association

Death cases after vaccination:with vaccination, and reported cases were disclosed as in the

The risk of myocarditis death from SARS-COV-2 vaccines

summary list. However, not all serious reactions following

was calculated based on the death cases reported on “Thevaccination were disclosed. In other words, only death cases

summary of spontaneous cases reported as deaths afterin which doctors suspect the association were disclosed as inreceiving SARS-COV-2 vaccine” disclosed by the panels of

the summary list [5]. Some cases were reported beyond 28

experts on vaccination and adverse reactions under MHLW

days. After excluding cases in which the dates of vaccination,(Feb. 18th, 2022) [5] Deceased vaccinees who had received firstdate of death and the number of doses were unknown, theand/or second dose were analysed. By excluding duplicatedaverage number of days to death was 9.6 after the first dose

cases or withdrawals, 1,384 deaths after Pfizer vaccine, 66

and 11.6 after the second dose. The second dose is usuallydeaths after Moderna vaccine, and 1 death after AstraZeneca

given 21 days after the first dose. Therefore, the average

vaccine were examined (total 1,451 deaths).

number of days to death after the first dose were 32.6 days.

Myocarditis death cases after vaccination:

The distribution of the number of days to death in all cases is“Myocarditis death case” after vaccination was defined

shown in Supplementary Figure 1 and Supplementary Figure2.

as the cases in which “myocarditis” was described in the

Figure: Myocarditis mortality after SARS-CoV-2 vaccination（comparison with general population in 2019 as reference）
A: Myocarditis mortality ratepys: person-years

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B: Relative risk of myocarditis mortality

Adverse Reactions
Table 2: Myocarditis death cases after vaccination and in the reference population*a:Methods of calculation: See Table 1*b: For 95% confidence interval of mortality rate ratio of myocarditis death, including suspected case, and all-cause death, see Figure B, supplementary Fig
3B and supplementary Fig 4B respectively.

Calculation of person-years after vaccination:
Person-years to death after vaccination among vaccinees

included, it was 35-fold, 16-fold and 6-fold in 20s, 30s and
40s, respectively (See Supplementary Figure 3).

were calculated, based on the number of SARS-COV-2
vaccinees by 10-year age classes as of February 14th, 2022,

Figure B shows risk ratio (mortality rate ratio) and their

published by the cabinet office. The average number of days

95% confidence interval. Myocarditis mortality in the post-

to death were also calculated (Table 1).

vaccinated population were all statistically significantly higher
compared to the reference population in the 20s, 30s and 40s.

Myocarditis mortality in the reference population
Mortality rates of acute myocarditis (I40, ICD-10) in 2019was computed from the number of I40 death in the vitalstatistics and estimated population by 10-year age classes [6,7],

Actual myocarditis mortality might be evenhigher
The following 3 points should be considered when

and were used as the reference mortality rates by age.

interpreting these results.

Myocarditis death cases by age (after vaccination

1) Omission of reporting death cases (see Web Med

and in the reference population)

Check No.195 [8])Number of myocarditis death cases after vaccination and

Doctors are not obliged to report all post-vaccination deaths

that of the reference population based on the 2019 vitalin Japan [9]. In fact, there was a case which was reported only

statistics by 10-year age classes are shown in the Table 2 .

after the doctor was pressured by the bereaved family [10].
There was a case of a 55-year-old woman who died fromMarkedly high risk of myocarditis death in 20s

subarachnoid hemorrhage 5 days after vaccination. This caseand 30s adults

was once reported as a death case, but was withdrawn later. In

Figure A shows the comparison of myocarditis mortality

other words, post-vaccination death cases had been disclosed

rates after vaccination and that in the reference population by

only partially in Japan. According to the Centers for Disease

10-year age classes. It is very clear that myocarditis mortality

Control and Prevention (CDC) of United States of America

rates were higher than in the reference population especially(US), by the end of February 2022, about 550 million doses

in 20s and 30s. Myocarditis mortality rate was 0.16 persons

had been administered, and about 13,000 deaths had beenper 1 million person-years in 20s in the reference population.

reported after vaccination [11]. On the other hand, the number

However, after SARS-CoV-2 vaccination, it was about 20-foldof reported death cases were only about 1,500 cases while(3.3 persons per 1 million person-years) in 20s, about 14-foldabout 220 million doses had been administered in Japan.

in 30s, and about 5-fold in 40s. When suspected cases were

If death cases are reported as frequently as in the US, the
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Aug. 2022/ Vol.9 No.24 ・ Page 21

COVID-19 Information
number of death cases would be about 3.5-times higher than3) Information bias due to misclassification of

those disclosed in Japan.

causes of death [16]:A Korean case report was the case which was first reported

2) Healthy vaccinee effects (frailty exclusion bias)

as sudden death, but later diagnosed as myocarditis at autopsy[12]:[3]. Considering that there are many cardiovascular deaths in

The package inserts of SARS-COV-2 vaccines warn

the vaccinated [17], myocarditis might have been the causethat administration to persons with a serious acute illnessof death after vaccination in cases which was reported as

or a history of hypersensitivity was inappropriate [13, 14].

“cardiac arrest”, “sudden death” or “arrhythmia”. Israeli study

Furthermore, considering that myocarditis was listed as areported that overreporting may not explain high rate ratio of“serious adverse reaction”, administration to patients withmyocarditis after SARS-CoV-2 vaccination [2].

a heart disease or other serious illnesses would be avoided,

Considering the above 3 points, namely omission ofand thus both total mortality and myocarditis mortality due toreporting, healthy vaccinee effects (frailty exclusion bias) andvaccination could be underestimated.

misclassification of causes of death, it can be inferred that

The decisive evidence on healthy vaccinee effects (frailty
exclusion bias) was revealed in the analysis of the data from themortality rate of myocarditis after vaccination would be evenhigher than the results shown here.

UK [15]. The age-adjusted mortality rate of non-COVID-19related causes in 2021, which vaccination would not reduce,

The harm and benefit of SARS-COV-2 vaccines

to the estimated age-adjusted mortality rate in 2021was 0.2-

are needed to consider

fold (one-fifth) in those who had received the second dose at

It has already been revealed that SARS-COV-2 vaccines

the beginning. Age adjusted mortality rate was 1.8-fold incontribute to increased hemorrhagic stroke mortality [8,17]. It

unvaccinated persons over the year 2021, and 0.83-fold at thehas been also suggested that they are associated with deaths

beginning of vaccination and 2.6-fold over the year 2021 infrom arterial diseases, pulmonary venous thrombosis, andthose who had received first dose (those who could not have thepulmonary embolism [17].

second dose) [15].

This article showed that myocarditis mortality rate

The reason why the mortality rate of non-COVID-19-

increased especially in young adults after administration ofrelated causes, which vaccination would not reduce, was

SARS-COV-2 vaccines. The harm and benefit of the vaccines

lower among those who had received second dose is because

should be carefully considered in the light of these findings.

they had been healthier since before the vaccination and wereable to receive second dose as they had no problem after
first dose. Mortality rates over the year in the unvaccinatedand those who received only first dose were high because
the former originally more included those who had healthproblems which prevented them from vaccination (dying or
critically ill persons would not be vaccinated), and the latter may

have had experienced severe adverse reactions after the first
vaccination (see Web-Med Check No. 203 [15] for details andp●-● of this issue).

In Japan, the total mortality rate after vaccination was onetenth to one-hundredth of the total mortality of the reference
population (one-fortieth in all age groups) (see Supplementary
Fig.4,). This result suggests that there were many unreported

death cases in addition to healthy vaccinee effects (frailty
exclusion bias).

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Adverse Reactions
References
1) Japanese Cabinet Office: About COVID-19 vaccine in Japanese (accessed
2022.2.20)
https://www.kantei.go.jp/jp/headline/kansensho/vaccine.html
2) Mevorach D, Anis E, Cedar N, et al. Myocarditis after BNT162b2 mRNA
Vaccine against Covid-19 in Israel. N Engl J Med. 2021; 385(23):2140-2149.
3) Choi S, Lee S, Seo JW, et al. Myocarditis-induced Sudden Death after
BNT162b2 mRNA COVID-19 Vaccination in Korea: Case Report Focusing
on Histopathological Findings. J Korean Med Sci. 2021; 36(40):e286.
Published 2021 Oct 18.
4) MHLW COVID-19 vaccine Question and answers in Japanese (accessed
2022.2.20)
https://www.cov19-vaccine.mhlw.go.jp/qa/0079.html
5) Japan’s MHLW Database, in Japanese (accessed 2022.2.20)
https://www.mhlw.go.jp/stf/shingi2/0000208910_00038.html
6) Vital statistics in 2019: Causes of death by age, in Japanese (accessed
2022.2.20)
https://www.e-stat.go.jp/stat-search/files?page=1&layout=datalist&touke
i=00450011&tstat=000001028897&cycle=7&year=20190&month=0&tclas
s1=000001053058&tclass2=000001053061&tclass3=000001053065&result_back=1&tclass4val=07) Population estimates as at 1 October in each year in Japanese (accessed
2022.2.20)
https://www.e-stat.go.jp/stat-search/files?page=1&layout=datalist&touk
ei=00200524&tstat=000000090001&cycle=7&year=20190&month=0&tcla
ss1=000001011679
8) Med Check editorial team. Four women died of hemorrhagic stroke. Twotimes followed by a total of four times, with a strong causal relationship.
Web Med Check No195 in Japanese (accessed 2022.2.20)
https://npojip.org/sokuho/210426.html
9) MHLW: Call for spontaneous reports based on the vaccination law frommedical doctors (accessed 2022.2.20) https://www.mhlw.go.jp/bunya/kenkou/
kekkaku-kansenshou20/hukuhannou_houkoku/index.html
10) News paper “Yomiuri shinbun” on May 9 2021(accessed 2022.2.20)
https://www.yomiuri.co.jp/medical/20210508-OYT1T50380/
11) CDC. Selected Adverse Events Reported after COVID-19 Vaccination(accessed 2022.3.6)
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.
html12) Med Check editorial team. Basic principles in Medical research Supplementary material to Med Check No92 in Japanese (accessed 2022.3.6)
https://www.npojip.org/chk_tip/2020No92-furoku.pdf
13) Pckage insert of Pfizer vaccine “Cominarty” in Japanese (accessed
2022.2.20)
https://www.kegg.jp/medicus-bin/japic_med?japic_code=00069248 Thisissue): ●-●.
14) Pckage insert of Moderna vaccine “Spikevax” in Japanese (accessed
2022.2.20)
https://www.info.pmda.go.jp/go/pack/631341EA1038_1_02/
15) Med Check editorial team. Solid evidence for “healthy vaccinee effect”
Web Med Check No203 in Japanese
https://www.npojip.org/sokuho/220427.html Med Check in English. 2022:
8(24) (
16) Rothman KJ, Greenland S and Lash TL eds Modern Epidemiology 3rd ed.
Wolters Kluwer/ Lippincott Williams & Wilkins, 200817) Med Check editorial team. Strong association with cardiovascular deathespecially hemorrhagic stroke and venous thrombosis. Med Check in
English. 2022: 7(21/22): 32-37.
www.npojip.org/english/MedCheck/Med%20Check%20Tip-21-2021-08&12.
pdf

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Review

Non-COVID-19-related deaths were reduced in
the vaccinated population
Robust evidence for healthy vaccinee effectTranslated from Web Med Check (in Japanese) No 203. 27 April 2022
Med Check Editorial Team

Abstract
Vaccinees are generally healthier than non-vaccinees. When study results are distorted (biased) because ofthis, it is generally called “healthy vaccinee effect” or “healthy user bias”. This article discusses this issue basedon the data on mortality rates in the vaccinated and the non-vaccinated population in the UK.
The mortality rate of non-COVID-19-related deaths, which vaccination would not reduce, was 0.2-fold (onefifth) of the 2021 estimated age-adjusted mortality rate in persons who had received 2 doses at the beginning of

the COVID-19 immunization program in UK. On the other hand, it was 1.8-fold over the year (2021) in the nonvaccinated, and 2.6-fold over the year in those who had received only 1 dose (those who could not receive thesecond dose).

The reasons why the mortality rate, which vaccination would not reduce, was lower in those who had received
the second dose is because they had been very healthy since before the vaccination and was able to receive thesecond dose as they had no problem with the first dose.
Mortality rates over the year in the non-vaccinated and those who had received only the first dose were highbecause the former originally had health problems, and the latter may have had experienced severe adverse
reactions after the first vaccination, and this contributed to high mortality rate of non-COVID-19-related deaths.

Keywords:
healthy user bias, age-adjusted mortality rate, first dose, second dose, UK, COVID-19 related death, all-cause mortality

tendency that vaccinees are originally healthier than non-Introduction

vaccinees is called “healthy vaccinee effect” or “healthy

Med Check No.101 [1] reported that mortality rate fromuser bias” in epidemiology. Especially in studies on harm

myocarditis after COVID-19 vaccination was higher by 14 toand effect of vaccines, data must be carefully examined,

20 times in the vaccinees in their 20s to 30s as compared toconsidering the influence of this bias.

the general population. This can be even higher, considering

However, in most epidemiological studies on vaccines, itthat there were unreported deaths, vaccinees were originallyis ignored, although many baseline characteristics including

healthier than non-vaccinees, and some cases of myocarditis

age, sex, comorbidities or socioeconomic characteristics are

were reported as arrhythmia or sudden death (misclassification).

adjusted. Vaccinees many of whom are healthy and non-People who have severe illness especially who are about tovaccinees many of whom have illnesses are compared without

die or fever on that day would avoid vaccination. Therefore,

adjustment of real health condition to conclude that vaccines

vaccinees are generally healthier than non-vaccinees. For thisare “effective” and “not harmful”.

reason, if morbidity rates of illnesses they would have after

While the issues of omission of reporting andvaccination in the vaccinated and non-vaccinated are directly

misclassification are relatively easy to understand, “healthy

compared, the result would not reflect the reality.

vaccinee effect” is not well recognized even among experts

As explained above, the bias or distortion created by the

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despite its significance. One of the reasons why it is notwidely recognized as important, even though it is not soGenerally, this phenomenon is called “healthy vaccineedifficult to understand, is that it has not been theoreticallyeffect”. When this concept is extended to include not only

examined well.

vaccines but also other medicines, a term “healthy user bias”

Moreover, one of the most important reasons is that if

is more appropriate.

“healthy vaccinee effect” is rightly adjusted in epidemiologicalOn the other hand, focusing on the tendency that frail

studies, evaluation of many vaccines would be overturned:

people avoid vaccination, a term “frailty selection bias” isthose which have been considered “effective” and “notalso used. However, this term may cause misunderstanding

harmful” would be “ineffective” and “harmful”.

that “frail people are selected to be vaccinated”. Actually,

Panels of experts of many countries as well as international

there was a paper which misunderstood the term. Therefore,

organizations, such as World Health Organization (WHO),Med Check No.65 (May 2016) proposed to use the term “frailty

have been assessing vaccines as “effective” and “not harmful”

exclusion bias” in its analysis on HPV vaccines [4].

based on the studies in which “healthy vaccinee effect” is not

However, as the term “healthy vaccinee effect” is moreconsidered. However, if “healthy vaccinee effect” is rightly

widely accepted even by doctors, Med Check has been using

adjusted, the results would be overturned. Because of this,the term “healthy vaccinee effect (frailty-exclusion bias)” sincemost epidemiological studies on harm and effectiveness ofthen.

vaccines ignore this bias, and unscientific research results are

Therefore, “healthy vaccinee effect” and “frailty-exclusion

published as academic peer-reviewed papers and adopted inbias” are two sides of the same coin, looking at the same

policy making of national governments and WHO. As long

phenomenon from the viewpoints of those who receive oras this would continue, adjusting “healthy vaccinee effect” inavoid vaccination.

epidemiological studies would not be understood reightly andsupported by the majority of people.
In reality, as Med Check has pointed out in its Web Med
Check No. 198 “Harm and benefit of HPV vaccines” andThis article discusses that healthy vaccinee effect (frailtyexclusion bias) clearly has influence on the studies of

COVID-19 vaccines, using the data on the mortality rates in
the UK.

No.199 “Resumption of HPV vaccines is very dangerous”[3], there is strong influence of “healthy vaccinee effect” on【2】Overview of the method

evaluation of seemingly effective and safe vaccines.

(1) Basic method

As regard to HPV vaccines, the study result was distorted.

The basic method used to examine healthy vaccinee effectBecause frail people avoid vaccination while healthy people(frailty-exclusion bias) in studies on COVID-19 vaccines is as

receive vaccination (the vaccinated is healthier than the non-follows;

vaccinated), non-HPV-related cancers, which HPV vaccine

A. The 2021 age-adjusted mortality rate in the UK is estimatedwould not prevent, are reduced in the vaccinated population.

based on the national statistics data up to 2019 [6].

Furthermore, various other harms are reduced in the

B. We noticed especially the non-COVID-19-related age-

vaccinated population because of the influence of the bias.

adjusted mortality rates by vaccination status (non-vaccinated,

This article explains this important issue, “healthy vaccinee

1 dose or 2 doses or booster dose).

effect” or “healthy user bias” or “frailty-exclusion bias” andC. Ratio of the above two mortality rate (mortality rate ratio) is

shows that it is clearly at work in the studies on COVID-19

calculated and compared. [7,8].

vaccines.
(2) Mortality rates of non-COVID-19-related deaths are【1】Healthy vaccinee effect and frailty-exclusion bias

mainly compared.

Frail people avoid vaccination and healthy people receive

As of the age-adjusted mortality rates, not only total

vaccination, resulting in overestimation of effect andmortality rate, but also mortality rate of COVID-19 as wellunderestimation of harm [2-5].

as that of non-COVID-19-related deaths were reported.

Distortion of results or yielding results different from the[8] Among them, non-COVID-19-related death was thetruth is called “bias” in epidemiology. Causes of such a bias

main focus of this analysis, Mortality rate of non-COVID-

are shown in details in another article in this issue.

19-related deaths may increase if COVID-19 vaccines are

MED CHECK

Aug. 2022/ Vol.9 No.24 ・ Page 25

Review
harmful. It may also increase when COVID-19

Figure 1: Method for estimation of age-adjusted mortality rate in 2021

deaths are classified as non-COVID-19-related
deaths. However, it would not be reduced by thevaccines. Therefore, this article focuses on themortality rates of non-COVID-19-related deaths.
(3) Monthly age-adjusted mortality rate is used
Monthly age-adjusted mortality rates in thevaccinated and the non-vaccinated (by the numberof doses) reported in the database [8] based on

person-years and the number of deaths are usedin our analysis.

*a：The line is the extension of the regression line of 2010-2019 age-adjusted mortality
rates. 〇：The Estimated rate in 2021 is 932/100,000 person-years.

(4) Mortality rates within and more than 20days after vaccination are also compared
As regard to the vaccinated, age-adjusted mortality rates
were reported for within 20 days of the first dose and for 21(2) Daily number of COVID-19 deaths vaccinated andpercent with full dose.

days or later after the first dose, within 20 days of the second

Figure 2 shows the trend of daily number of COVID-19

dose and for 21 days or later after the second dose, and within

deaths, daily number of vaccinated and percent who received

20 days of booster (third) dose and for 21 days or later after

full dose of SARS-CoV-2 vaccine in the UK in 2021. The data

the booster (third) dose.

source is Our World in Data (OWID), Coronavirus Pandemic

The meaning behind these differences is explained below:
1) Most deaths within 20 days of the first dose occurred before(COVID-19) [7].

In the UK, daily number of COVID-19 deaths reached its

the second dose.

peak on 20 January 2021 during the rhird wave of COVID-19

2) Deaths which occurred 21 days or later after the first doseand it was reduced from April to June, 2021.

are the deaths of those who could not receive the second dose

Apparently, it was reduced as the vaccination rate increased,

mainly for health reasons.

but considering the situations in other countries, it cannot be3) Deaths which occurred within 20 days of the second dosethe effect of vaccination (Note 1).

and 21 days or later after the second dose are the deaths ofhealthy people who were able to receive 2 doses as they had
no problem with the first dose. However, they avoided booster

Note 1: For example, in Singapore, SARS-CoV-2 immunization was
actively promoted, and the vaccination rate for the second dose wasover 70% in August, 2021. However, especially around that time, adose for health reasons.

major pandemic began and the mortality rate was as high as 100/100

4) Those who received the third dose are healthy people who

million persons in the end of September, and 400/100 million persons

were able to have the second dose without problem.

【3】Results and Discussion(1) Estimated age-adjusted mortality rate for 2021

in November. Moreover, the vaccination rate of booster shots wasover 50% in the mid-January, 2022 and reached 69% in the end of
February. On the other hand, the numbers of infected people anddeaths was 20 times higher in the end of February than those in the
mid-January. The number of infected people reached its maximum of

The following data of the UK Office for National Statistics

about 40,000 persons in one day. This is equivalent to 800,000 persons

are used to calculate the estimated age-adjusted mortality

in the Japanese population. This shows that COVID-19 vaccines did notrates, assuming that there was no pandemic of COVID-19 in
2021 Dataset: Deaths registered in England and Wales

contribute much to prevent the pandemic and deaths unlike suggested
by randomized controlled trials (RCTs) (see slide 18).

The regression line of 2010-2019 age-adjusted mortality

It is noteworthy that daily number of COVID-19 deaths inrates (y = -6.3552x + 13776) is extended to meet the year 2021 at

the UK was very low from April to June. As explained below

932/100,000 person-years. This is considered as the estimatedin detail, this should be examined in contrast with the fact thatage-adjusted mortality rate for the year 2021 (Figure 1).

during this period in the UK, mortality rates of non-COVID-

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Aug. 2022/ Vol.9 No.24

19-related deaths increased

Figure 2: Trend of the daily COVID-19 deaths, daily number of vaccinated and percent who
received full dose of SARS-CoV-2 vaccine.

in the non-vaccinated and 21days or later after the 1st dose.
(3) Age-adjusted mortality
rate of non-COVID-19related deaths
COVID-19 vaccines are
believed to be effective
in reducing onset andaggravation of COVID-19(infection caused by SARSCoV2), and thus reduce deaths.

Its efficacy on reducing onset
and aggravation is proven by
RCTs.
H o w e v e r, t h e y a r e n o t
supposed to reduce non-

Data source：Our world in Data(OWID)、Coronavirus Pandemic (COVID-19)
https://ourworldindata.org/coronavirus#explore-the-global-situation.
*a: Number of COVID death is very few.
*b: Full-vaccinated means 2 doses for the most SARS-CoV-2 vaccine except one product which require only
one dose. The actual numbers of daily deaths and vaccination fluctuate greatly. Smoothed figures, which
are calculated using figures before and after the original figures, are used in this analysis. The number of
COVID-19 deaths was very small from April to June 2021.

COVID-19-related deaths,
such as other infections, heart diseases and cancers, while they

reduction due to the healthy vaccinee effect (frailty-exclusion

can increase these illnesses as adverse effects.

bias).

The source of data used for this analysis is Office for

Therefore, if the mortality rate of non-COVID-19-related
deaths in the non-vaccinated is higher than the 2021 estimatedNational Statistics Dataset [8].

age-adjusted mortality rate, the increase can be attributed to1) The mortality rate of non-COVID-19-related deaths in

the increase due to the effect of frailty-exclusion bias (healthy

the non-vaccinated (Figure 3)
Figure 3 shows the following:

vaccinee effect).

In addition, if the mortality rate of non-COVID-19-related

A. monthly age-adjusted mortality rates of non-COVID-19-

deaths in the vaccinated is lower than the 2021 estimated age-

related deaths and the 2021 estimated age-adjusted mortality

adjusted mortality rate, the reduction can be attributed to therate as reference, andFigure 3: Non-COVID-19-related deaths in unvaccinated population

From April to June, when there were very few COVID-19 deaths, the mortality rate ratio of non-COVID-19-related deaths to the estimated mortality
rate in the non-vaccinated was average 1.9 (*a). This indicates that mortality rate in the non-vaccinated doubled due to frailty-exclusion bias.

MED CHECK

Aug. 2022/ Vol.9 No.24 ・ Page 27

Review
Figure 4: non-COVID-19-related deaths after second and third doses

The mortality rates not only of COVID-19 (not shown in the figure 4, see Figure 8), but also of other illnesses (non-COVID-19 death) are markedly low
in the vaccinated people, especially in those who could receive second (*a) or third doses (*b) (healthy vaccinee effects)
Mortality rate is high in those who could not have 3rd dose after 2nd dose (*c). This is because they avoided 3rd dose due to health problems. →frailtyexclusion bias.

B. mortality rate ratio (risk ratio) of non-vaccinated population

who had received second dose was 0.2-fold (one-fifth) of theto the 2021 estimated age-adjusted mortality rate as reference

estimated mortality rate (Note 2). In other words, they were 5(1.0).

times healthier than the general population.

Mortality rates in the non-vaccinated people was constantly
higher than the estimated mortality rates from January toNote 2: Rate ratio of the mortality is 0.2 which is the average ofmortality rate ratio of non-COVID-19-related deaths within 20 days ofthe second dose (0.25) and that of 21 days or later after the second

December, 2021. The average mortality rate ratio was 1.77

dose (0.15). Details of statistical testing is omitted here, but it is certain

annually, and 1.9 between April and June, when the mortalitythat they are statistically significant.

rate of COVID-19 was extremely low. During the period
from mid-March to the end of June, excess mortality wasThis tendency is consistent with the fact that the mortality

almost minus according to OWID [9]. This means that higher

rate ratio at the initial stage of introduction of booster shots

mortality rate of unvaccinated in this period was not affectedwhich began in September 2021 was 0.2 (mortality rate wasby the excess death due to potential SARS-CoV-2 infection.

0.2-fold).

This is because many frail people might have avoided

It can be said that people who received the first vaccination

vaccination. In other words, it was the result of frailty-

early, and especially those who could receive second or

exclusion bias.

booster vaccination were originally very healthy.
Mortality rates of non-COVID-19-related deaths are2) Mortality rates of non-COVID-19-related deaths aftermarkedly low at the early stage after the second and third

the second and third doses

dose. This is exactly the effect of healthy vaccinee effect.

Fig.4 shows the following:

On the other hand, after the launch of booster shots began

A. age-adjusted mortality rates of non-COVID-19-related

in September, mortality rates drastically increased especiallydeaths after the second and third doses and the 2021 estimatedin those who died 21 days or later after the second dose. This

age-adjusted mortality rate as reference, andis because they had health problems and avoided the booster

B. mortality rate ratio (risk ratio) to the 2021 estimated age-dose. This is a typical example of frailty-exclusion bias inadjusted mortality rate (1.0).

which frail people avoid vaccination.

In the beginning of the immunization program, themortality rate of non-COVID-19-related deaths in thosePage 28 ・ MED CHECK

Aug. 2022/ Vol.9 No.24

Figure 5: non-COVID-19-related deaths after the first dose*a：At the initial stage of immunization program, the mortality rate within 20 days of the first vaccination was lower than the estimated mortality rate
(mortality rate ratio: 0.62) due to the healthy vaccinee effect.
*b：However, the mortality rate was very high in people who could not receive the second dose when there was not so many COVID-19 deaths andvaccination was active (mortality ratio: 5.4-6.8). This is probably because they became sick after they had received the first dose. In other words, they
were frail and excluded from vaccination (frailty-exclusion bias).

3) Mortality rate of non-COVID-19-related deaths afterrate after the first dose was lower than the estimated mortality

the first dose

rate. The mortality ratio within 20 days of the first vaccination

Figure 5 shows the following:
A. age-adjusted mortality rates of non-COVID-19-related
deaths after the first dose and the 2021 estimated age-adjusted

was 0.62. This suggests that the vaccinees were healthy until
this point.
However, the mortality rate ratio at 21 days or later after

mortality rate as reference, andthe first dose increased to 1.05. Usually the second dose is

B. mortality rate ratio (risk ratio) to the 2021 estimated age-

administered 21 days after the first dose. At this point, it isadjusted mortality rate (1.0).

highly likely that those who could not receive the second doseAt the initial stage of immunization program, the mortality

had had health problems after the first dose.

Figure 6: Mortality rate of non-COVID-19-related deaths by number of doses (summary)

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Aug. 2022/ Vol.9 No.24 ・ Page 29

Review
Figure 7: Mortality rate ratios of non-COVID-19-related deaths (summary)This tendency became especially evident between May to
July 2021, when there were very few COVID-19 deaths. The
mortality rates increased to as high as 5.4-fold to 6.8-fold of theestimated mortality rates.

5) Mortality rate ratio of non-COVID-19-related deaths (bythe number of doses)

Figure 7 shows mortality rate ratio of non-COVID-19related deaths to the 2021 estimated age-adjusted mortality

People who had received the first dose were relatively healthy.

rate (1.0) by the number of doses. Mortality rate ratios of non-Among them, some died without receiving the second dose.

COVID-19-related deaths by the number of doses shown in

It can be inferred that the additional deaths to the estimatedthe Figure 7 are the average of mortality ratios within 20 days

mortality rate might be caused by the vaccines.

and 21 days or later after vaccination.
People who were vaccinated with the first dose were4) Mortality rate of non-COVID-19-related death comparing

supposed to be healthier than non-vaccinated people at theby number of doses

initial stage of the immunization program. However, as the

Figure 6 summarizes age-adjusted mortality rate of nonCOVID-19-related deaths by the number of doses.

vaccination was promoted, high-risk people began to receive
vaccination. Among such people, there might have been many

Figure 8: Summary of trend in mortality rates of COVID-19, non-COVID-19-related deaths, and all-cause mortality rates

Page 30 ・ MED CHECK

Aug. 2022/ Vol.9 No.24

people who died within 20 days of the first dose, or died 21days or later after the first dose, while they avoided the second
dose because they had health problems after the first dose.
At least, the avoidance of the second vaccination is exactly
the phenomenon of frailty-exclusion bias. Moreover, there is apossibility that substantial part of avoidance was due to healthproblems caused by adverse effects of the vaccines.
This has been clearly observed in deaths 21 days or later

References
1) MedCheck Editorial Team. COVID-19 vaccine：Myocarditis mortality rate
rises, especially among people in their 20s and 30s. Med Check 2022：22(101)：70-72.
2) Hama R. Web Med Check No198（2021.12.28）、Benefits and Harms of
HPV Vaccines - Record of Hama’s lecture at "Japanese foundation for
Sexual Health Medicine" is released: https://www.npojip.org/sokuho/211228.
html
3) MedCheck Editorial Team. Resuming HPV vaccination is very dangerous.
Med Check in English 8(23): 3-10
https://www.npojip.org/english/MedCheck/Med%20Check%20TIp-23-202204.pdf

after the second vaccination since the administration of4) MedCheck Editorial Team. Symptoms after HPV vaccine: typical "frailty

booster shots began.

5) MedCheck Editorial Team. The core principle for “Medical Research

exclusion bias" in Nagoya City study. Med Check in English 2(5): 18-21
Methods”：Supplement for MedCheck No92

6) Mortality rates of COVID-19 and non-COVID-19related deaths, and all-cause mortality rate (by the numberof doses)

Finally, trend in mortality rates of COVID-19, nonCOVID-19-related deaths, and all-cause mortality rates are
summarized by the number of doses in Figure8.
This article pointed out that healthy vaccinee effect (frailtyexclusion bias) has clearly influenced mortality rates of non-

(In Japanese): https://www.npojip.org/chk_tip/2020No92-furoku.pdf6) Office for National statistics, Dataset：Deaths registered in England andWales
https://www.ons.gov.uk/peoplepopulationandcommunity/
birthsdeathsandmarriages/deaths/datasets/deathsregisteredinenglandandw
alesseriesdrreferencetables
7) Our world in Data(OWID)、Coronavirus Pandemic (COVID-19)
https://ourworldindata.org/coronavirus#explore-the-global-situation
8) Office for National Statistics, Dataset、Deaths by vaccination status,
Englandhttps://www.ons.gov.uk/peoplepopulationandcommunity/
birthsdeathsandmarriages/deaths/datasets/deathsbyvaccinationstatusengland

COVID-19-related deaths. Similar influence can be observedin mortality rates of COVID-19, and thus all-cause mortality
rates, in which the former and the latter are combined.
Mortality rates of COVID-19 in the vaccinated seem to bemarkedly lower than that in the non-vaccinated. However, it
should be noted that the mortality rates in the non-vaccinatedare overestimated by about 2 times, and the mortality rates inthose who received 2 doses are underestimated by one-fifth.

Conclusion
The mortality rate of non-COVID-19-related deaths,
which vaccine does not reduce, was 0.2-fold of the
expected age-adjusted mortality rate in full vaccinated. It
was 1.8-fold in the non-vaccinated, and 2.6-fold in those
who had received 1 dose.
The reasons why the mortality rate was lower in theformer is because they had been very healthy and could
receive 2 doses as they had no problem after the first
dose. Mortality rates in the non-vaccinated and those
who had received only one dose were high because theformer originally had health problems, and the latter may
have had experienced severe adverse reactions after
the first dose, and this contributed to high mortality rateof non-COVID-19-related deaths. These indicate robust
healthy vaccinee effect with SARS-CoV2 vaccine.

MED CHECK

Aug. 2022/ Vol.9 No.24 ・ Page 31

NEWSImbalance in baseline characteristics in molnupiravir trials
This is a letter [1] which summarize the article [2,3] criticizing the serious flaw of molnupiravir trials by MedCheck
editorial team and was published as a letter to the editor of BMJ. It is a free access article and we introduce in thisissue of MedCheck in English.

Page 32 ・ MED CHECK

Aug. 2022/ Vol.9 No.24

Review

Why do vaccine look effective?

Another evidence of healthy vaccinee effectTranslated from Web Med Check (in Japanese) No 205. 30 August 2022
Med Check Editorial Team

Abstract●In spite of frequent inoculation of SARS-CoV-2 vaccine, the Omicron variant epidemic has progressed world
widely, and monoclonal antibody products are all ineffective to this variant except one which is unavailable inJapan. These suggest that the vaccine is ineffective for prevention of COVID-19.
● However, vaccination is being promoted based on epidemiological studies in which authors claim that vaccine iseffective to reduce COVID-19, especially severe cases by more than 90%.
●Analysis by MedCheck team using the data from the UK statistics revealed the presence of a healthy vaccinee
effect（frailty exclusion bias）on non-COVID-19 death in SARS-CoV-2 vaccine users as compared to theunvaccinated（p24 in this issue）.
●This article analyses the data of the epidemiological survey from Israel, and found that on the day of vaccination,
the vaccinee had lower incidence of COVID-19: asymptomatic infection by 38%, symptomatic infection by 60%,
hospitalised COVID-19 by 73%, severe COVID-19 by 83% and death due to COVID-19 by 87%. These are theresults simply due to the fact that the vaccinees were healthier than the unvaccinated.
●Reduction of severity by 80% to 90% in epidemiological surveys may simply be the results of healthy vaccinee
effect. We should not be fooled by experts' explanations.

Keywords:
SARS-CoV-2 vaccine, COVID-19, asymptomatic, symptomatic, hospitalisation, severe COVID-19, death, epidemiological study, frailty
exclusion bias.

Introduction

on the Omicron variant [2-4] also suggest that the SARSCoV-2 vaccine is ineffective against the Omicron variant,

The SARS-CoV-2 vaccine is almost ineffective against

because antibody products were produced as the monoclonal

COVID-19 infected by the SARS-CoV-2 Omicron variant

antibody of original SARS-CoV-2 (Wuhan) strain and SARS-

that has caused a global pandemic from the end of 2021 to

CoV-2 vaccines were also produced to induce antibody ofthe end of August 2022. In Singapore, the booster vaccination

original SARS-CoV-2 (Wuhan) strain.

rate reached 70%, but at its peak of epidemic, 40,000 people

However, epidemiological studies have reported high(equivalent to 0.8 million for the Japanese population) wereeffectiveness even on the Omicron variant [5-7]. In Japan, it

confirmed having COVID-19 in one day. In South Korea as

has been reported that vaccine effectiveness is nearly 90%

well, 0.62 million people (1.5 million for Japanese population)

against Delta variant infection, approximately 50% after the

had COVID-19 in one day at the peak, although 63% of thesecond dose, and 74% after the third dose against Omicron

population had received booster dose [1]. Now one in 2.2

variant infection, showing high effectiveness [7].

people had been confirmed having COVID-19 in Korea. TheseIn particular, vaccine effectiveness is reportedly 99% (Delta

suggest that the vaccine is ineffective against the Omicron

variant) and 95% (Omicron variant) in severe cases, including

variant.

fatal cases. Based on such data, many countries still strongly

Ineffectiveness of almost all monoclonal antibody products

recommend vaccination.

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Aug. 2022/ Vol.9 No.24 ・ Page 33

Review
Although the situation of the epidemic suggests that thetables are reported, including the number at risk, the number

SARS-CoV-2 vaccine is not effective as described above, theof events, the number censored by daily basis, by vaccination

epidemiological surveys show apparent effectiveness even on

status (vaccinated and unvaccinated) and by event typethe Omicron variant. One of the most important reasons for(documented SARS-CoV-2 infection, symptomatic COVID-19,

this discrepancy may be because observational studies do not

COVID-19 hospitalisation, severe COVID-19 and death due totake “healthy vaccinee effect” (p 24 of this issue) into account.

COVID-19)from the day of vaccination (day 1) to day 44. The

This article presents the results of an analysis ofincidence rate of "asymptomatic SARS-CoV-2 infection"

epidemiological study from Israel: although the vaccine does（/100,000 person-days (pd)）was calculated by the numbers of

not work on the day of vaccination, the results show that thedifference between all documented SARS-CoV-2 infection

vaccinee’s incidences of asymptomatic infection, symptomaticand symptomatic COVID-19.

infection, hospitalization, severe disease and death were

The daily incidence rates of event (/100,000 pd) comparing

reduced by 38%, 60%, 73%, 83%, and 87%, respectively. We

the vaccinated and the unvaccinated for 1 week after the firstwill explain how these data were obtained from the original

inoculation are shown in the Figure 1 (asymptomatic SARS-

paper and will discuss what these mean.

CoV-2 infection: Figure 1 A and symptomatic Covid-19: Figure 1 B).

Incidence rates are lower in the vaccinated group thanIsrael survey

the unvaccinated group on day 1 especially of symptomatic

A nation-wide cohort study to evaluate the effectiveness of

Covid-19.

the SARS-CoV-2 vaccine was conducted in Israel [8]. About

Incidence rates of asymptomatic infection (/100,000

600,000 people each were selected from vaccinated and non-pd) were 14 and 22 for the vaccinated and unvaccinatedvaccinated population during the period from 20 December

groups, respectively (difference is 8/100,000 pd), while those2021 to 1 February 2021. The vaccine effectiveness wasof symptomatic COVID-19 were 15 and 38, respectively

assessed by SARS-CoV-2 infection at day 7 or later after(difference is 23/100,000 pd). These indicate that vaccinatedthe second dose of vaccine, and it was 92% for documented

group has lower risk of SARS-CoV-2 infection.

infections, 94% for symptomatic COVID-19, 87% for
hospitalised COVID-19, and 92% for severe COVID-19.
Effectiveness for death was reportedly not assessed.

Risk increases until second week
In the unvaccinated population, incidence rate (/100,000 pd)
is almost consistent at around 25 for asymptomatic infection

Fewer illnesses from the day of inoculation
In the supplementary material of the report, precise lifeand 40 for symptomatic COVID-19.
In the vaccinated population, incidence is the lowest on day

Figure 1: Daily incidence rates of COVID-19 by vaccination status up to day 7

Calculated by MedCheck team from the data in the supplementary Table S7 in ref [8].

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Aug. 2022/ Vol.9 No.24

Figure 2: Odds ratios of COVID-19 by time from first inoculation by severity

Calculated by MedCheck team from the data in the supplementary Table S7 in ref [8].

1 and the difference is the largest on day 1. It increased andinfection was 0.91 (0.83, 1.00) and that of the second week

almost reached the incidence of the unvaccinated on day 5

was 1.11(1.00, 1.23) (Figure 2A). For symptomatic COVID-19

and day 6. On day 7, it exceeded that of the unvaccinated for

average odds ratio was 0.78 (0.72, 0.84) and 1.02 (0.96, 1.08),

asymptomatic infection (37 and 28, difference was – 9/100,000

respectively (Figure 2B).

pd) (Figure 1A) . For symptomatic COVID-19, it slightly

exceeded unvaccinated population on day 7 (47 and 46,

Estimation of odds ratio on day 1 fordifference was –1/100,000 pd) (Figure 1 B).

hospitalisation, severe case and deathLet's take a look at the odds ratios of hospitalised

Odds ratios of COVID-19 by time from first

COVID-19 or other severer COVID-19 patients. In the

inoculation by severity

unvaccinated population, hospitalisation occurred from day

Figure 2 shows odds ratios (ORs) of the vaccinated to1, but in the vaccinated population, hospitalisation did not

the unvaccinated by time (days) from the first inoculation

occur until day 3. Severe COVID-19 occur from day 3 inof vaccine, by severity of SARS-CoV-2 infection: A.

the unvaccinated, while it did not occur until day 6 in theasymptomatic infection, B. symptomatic COVID-19, C.

vaccinated. There was 1 death on day 7, and 6 deaths by day

hospitalised COVID-19, D. Severe COVID-19 and E.

14 in the unvaccinated, but 0 by day 10 and only 2 deaths in

Death due to COVID-19.

the vaccinated population by day 14 (1 each on day 11 and 14).

On day 1, OR was 0.62 (95% CI: 0.47, 0.82) for
asymptomatic infection and 0.40 (0.31, 0.51) for symptomatic

According to the raw data, the odds ratio for hospitalization

COVID-19 (Figure 2A and 2B). Both ORs were statisticallyis 0. Because the number of severe COVID-19 and deathsignificant.

due to COVID-19 was 0 in both groups (vaccinated andOdds ratio increased as the day passed and exceeded 1.0 andunvaccinated), OR cannot be calculated. Therefore, OR for thereached 1.34 (1.05,1.70) for asymptomatic infection and 1.03

hospitalised, severe cases and death due to COVID-19 on day(0.84, 1.25) for symptomatic COVID-19 on day 7.

1 was estimated by the following formulas:

Average odds ratio of the first one week for asymptomatic

MED CHECK

Aug. 2022/ Vol.9 No.24 ・ Page 35

Review
Figure 3: Odds ratio of COVID-19 on day 1 of vaccination

Calculated by MedCheck team from thedata in the supplementary Table S7 in
ref [8]. ※ : Since no event was recorded on
day 1 of inoculation for the hospitalized,
severe case or death due to Covid-19.
Odds ratio of these events on day 1 wasestimated from the data as described in
the text. Since it is impossible for thevaccine to be effective from the day of
vaccination, this apparent low risk does
not mean that the vaccine is effective butthat the vaccinated persons are at low
risk of disease and death compared tothe unvaccinated persons (or vaccinatedpersons are healthier than unvaccinatedindividuals), showing “healthy vaccinee
effect (or frailty exclusion bias)”.

OR (hosp. d1) = OR (hosp. d1-7) ×（OR(sympt.d1)/OR (sympt.

OR for asymptomatic infection, symptomatic COVID-19,

d1-7)） (1)hospitalized COVID-19, severe COVID-19 and death due to

OR (sever.d1) = OR (sever.d1-7) ×（OR(sympt.d1)/OR (sympt.

COVID-19 are 0.62, 0.40, 0.27, 0.18 and 0.13, respectivelyd1-7)） (2)(Figure 3).

OR(death.d1) = OR(death.d1-14) ×（OR(severe.d1)/OR(severe.
These data do not indicate the effectiveness of vaccine,

d1-14)） (3)but if this is described in terms of “vaccine effectiveness”,(1) OR of hospitalisation on day 1 (OR(HPd1)) is estimatedasymptomatic infections were reduced by 38%, symptomaticby multiplying the OR of hospitalisation during day 1-7

infections by 60%, hospitalization by 73%, sever COVID-19(OR(HPd1-7)) by the ratio of OR for symptomatic COVID-19

by 82%, and death due to COVID-19 by 87%.

on day 1 (OR(SYd1)) to that of day 1-7 (OR(SYd1-7)).
(2) For severe COVID-19, odds ratios on day 1 wasestimated by the similar method as (1).

Since it is impossible to have such an effect at day 1
after vaccination, this apparent "effectiveness" simply
indicates that the vaccinated persons were much healthier(3) Odds ratio for death due to COVID-19 on day 1 (OR(Dthan unvaccinated persons. It clearly creates the illusiond1)) was estimated by multiplying the OR of death during day

that the vaccine works very well especially on severe cases,

1-14 (OR(D d1-14)), by the ratio of OR for severe COVID-19

unless “healthy vaccinee effect (frailty exclusion bias)” ison day 1（OR(SVd1))(calculated by the formula (2)) to that oftaken into account.

day 1-14(OR(SVd1-14)).

Conclusion
The severer the symptoms, the lower the odds
ratio

Incidence rate of SARS-CoV-2 infection was lower
in the vaccinated population on the day of inoculation:

Figure 3 shows the results. The ORs for asymptomatic

Asymptomatic infection by 38%, symptomatic infection by

infection and symptomatic COVID-19 on day 1 odds ratios

60%, hospitalised COVID-19 by 73%, severe COVID-19

and their 95% confidence intervals (95%CI) for asymptomaticby 83% and death due to COVID-19 by 87%. These are

infection, symptomatic COVID-19 that are accurately

the results simply due to the fact that vaccinees were

calculable by raw data are 0.62 (0.47, 0.82) and 0.40 (0.31,

healthier than the unvaccinated. Reduction of severity

0.51) , respectively. However, 95%CI is not accurately

by 80% to 90% in epidemiological surveys may simply

calculated and it is not shown for hospitalisation, severe

be the results of “healthy vaccinee effect”. Hence, we

disease and death.

should not be fooled by experts' explanations based on the

Vaccinees showed significantly lower OR of COVID-19
on the day of vaccination (on day 1) than the unvaccinated.
Moreover, the OR decreased as the symptom became severer:
Page 36 ・ MED CHECK

Aug. 2022/ Vol.9 No.24

epidemiological study which ignored “healthy vaccinee
effect”.

References
1) Med Check editorial team. Editorial ”Vaccine cannot end the Covid-19
pandemic” MedCheck 2022: 22(101): 55 (in Japanese)
2) Bruel T, Hadjadj J, Maes P, et al. Serum neutralization of SARS-CoV-2
Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal
antibodies. Nat Med 2022. https://doi.org/10.1038/s41591-022-01792-5
3) Iketani S, Liu L, Guo Y, et al. Antibody evasion properties of SARS-CoV-2
Omicron sublineages. Nature 2022;604:553-6.
4) Takashita E et al. Efficacy of Antibodies and Antiviral Drugs against
Omicron BA.2.12.1, BA.4, and BA.5 Subvariants. NEJM 2022; 387:468-470
DOI: 10.1056/NEJMc2207519
5) Buchan SA, Chung H, Brown KA, et al. Effectiveness of COVID-19 vaccines
against omicron or delta infection. medRxiv. 2022. doi:10.1101/2021.12.30.2
1268565
6) Hansen CH, Schelde AB, Moustsen-Helm IR, et al. Vaccine effectivenessagainst SARS-CoV-2 infection with the omicron or delta variants following
a two-dose or booster BNT162b2 or mRNA-1273 vaccination series: A
Danish cohort study. medRxiv. 2022. doi:10.1101/2021.12.20.21267966 24
7) Arashiro T, Arima Y, Muraoka H. et al . COVID-19 vaccine effectivenessagainst symptomatic SARS-CoV-2 infection during Delta-dominant andOmicron-dominant periods in Japan: a multi-center prospective case-control
study (FASCINATE study). Clin Infect Dis. 2022. PMID: 35918782
8) Dagan N, Barda N, Kepten E et al. BNT162b2 mRNA Covid-19 Vaccine in
a Nationwide Mass Vaccination Setting. NEJM. 2021 Apr 15;384(15):14121423. doi: 10.1056/NEJMoa2101765.PMID: 33626250
9)Med Check editorial team. Web MedCheck No 205 (Aug 30) Why vaccine
looks like effective to prevent severe Covid-19？-Another evidence of
Healthy vaccinee effect.

M
C

ED

2022

Vol.9

No.24

HECK

Editor-in-Chief: HAMA, Rokuro (MD)
Deputy Editor: KIMOTO, Yasusuke (MD)Managing Editor: SAKAGUCHI, KeikoE d i t o r i a l S t a f f : N A K A N I S H I ,Ta ke a k i ( P h a r m a c i s t ) ; TA K A N O,
Yo s h i h i ko ( M D [ p e d i a t r i c i a n ] / P h a r m a c i s t ) ; U M E DA , Ta d a h i t o(MD[psychiatrist]) ;YANAGI, Motokazu (MD) ; YASUDA, Yoshinobu(Pharmacist)

Translators: NAKAMURA, Akari
Advisors:HONZAWA,Tatsuo (MD[GP]) ; IKEDA,Akiko (Pharmacist) ;KIM,Mieko (Pharmacist) ; KUDO,Shino (Pharmacist) ; MITA,Yasuko(Pharmacist) ; MUKAI, Junji (Pharmacist) ; SUMIDA, Sachie (MD[Dermatologist]); TERAOKA, Akio (Pharmacist) ; TOI, Chihiro (Pharmacist);
WADA,Masahide (MD[GP])Editorial Officer: SAKAGUCHI, Keiko
Production Team: UMEKI, Yukiko; SAKAGUCHI, Keiko; MATSUMOTO,
Koji
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