M
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August2022

Volume 9

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N 24r
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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. 24r）
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-19 death in vaccinated(2) Lower COVID-19 incidence at the day of inoculation

19
32

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 “unvaccinated” 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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Aug. 2022/ Vol.9 No.24 ・ Page 19

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 thanas sudden death, but later diagnosed as myocarditis at autopsy

those disclosed in Japan.

[3]. Considering that there are many cardiovascular deaths inthe vaccinated [17], myocarditis might have been the cause

2) Healthy vaccinee effects (frailty exclusion bias) [12]:of death after vaccination in cases which was reported as

The package inserts of SARS-COV-2 vaccines warn“cardiac arrest”, “sudden death” or “arrhythmia”. Israeli study

that administration to persons with a serious acute illness

reported that overreporting may not explain high rate ratio ofor a history of hypersensitivity was inappropriate [13, 14].

myocarditis after SARS-CoV-2 vaccination [2].

Furthermore, considering that myocarditis was listed as aConsidering the above 3 points, namely omission of“serious adverse reaction”, administration to patients with

reporting, healthy vaccinee effects (frailty exclusion bias) anda heart disease or other serious illnesses would be avoided,

misclassification of causes of death, it can be inferred thatand thus both total mortality and myocarditis mortality due tomortality rate of myocarditis after vaccination would be evenvaccination could be underestimated.

higher than the results shown here.

The decisive evidence on healthy vaccinee effects (frailty
exclusion bias) was revealed in the analysis of the data from the

The harm and benefit of SARS-COV-2 vaccines

UK [15]. The age-adjusted mortality rate of non-COVID-19

are needed to consider

causes in 2021, which vaccination would not reduce, to

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

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

contribute to increased hemorrhagic stroke mortality [8,17]. It

fold (one-fifth) in those who had received the second dose athas been also suggested that they are associated with deaths

the beginning. Age adjusted mortality rate was 1.8-fold infrom arterial diseases, pulmonary venous thrombosis, andunvaccinated persons over the year 2021, and 0.83-fold at thepulmonary embolism [17].

beginning of vaccination and 2.6-fold over the year 2021 inThis article showed that myocarditis mortality rate

those who had received first dose (those who could not have theincreased especially in young adults after administration of

second dose) [15].

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

The reason why the mortality rate of non-COVID-19
causes, which vaccination would not reduce, was lower among
those who had received second dose is because they had been
healthier since before the vaccination and were able to receive
second dose as they had no problem after first dose. Mortality
rates over the year in the unvaccinated and those who received
only first dose were high because the former originally more
included those who had health problems 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 (for details, see
Web-Med Check No. 203 [15] and p24-32 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).

3) Information bias due to misclassification of
causes of death [16]:A Korean case report was the case which was first reported

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Aug. 2022/ Vol.9 No.24

should be carefully considered in the light of these findings.

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 deaths were reduced in thevaccinated 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 the unvaccinated. 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 unvaccinated population in the UK.
The mortality rate of non-COVID-19-related deaths (non-COVID-19 death), which vaccination would not
reduce, was 0.2-fold (one-fifth) 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 unvaccinated, and 2.6-fold over the year in those who had received only 1 dose (those who
could not receive the second 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 unvaccinated 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 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 the

Introduction

unvaccinated 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 the unvaccinated, and some cases of myocarditis

age, sex, comorbidities or socioeconomic characteristics

were reported as arrhythmia or sudden death (misclassification).

are adjusted. Vaccinees many of whom are healthy and thePeople who have severe illness especially who are about tounvaccinated many of whom have illnesses are compareddie or fever on that day would avoid vaccination. Therefore,

without adjustment of real health condition to conclude thatvaccinees are generally healthier than the unvaccinated. For

vaccines are “effective” and “not harmful”.

this reason, if morbidity rates of illnesses they would have

While the issues of omission of reporting andafter vaccination in the vaccinated and unvaccinated are

misclassification are relatively easy to understand, “healthy

directly 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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Aug. 2022/ Vol.9 No.24

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 methods

evaluation of seemingly effective and safe vaccines.

(1) Basic methods

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(frailty-exclusion bias) in studies on COVID-19 vaccines is aspeople receive vaccination (the vaccinated is healthier thanfollows;

the unvaccinated) , non-HPV-related cancers, which HPV

A. The 2021 age-adjusted mortality rate in the UK is estimatedvaccine would not prevent, are reduced in the vaccinatedbased on the national statistics data up to 2019 [6].

population. Furthermore, various other harms are reduced in

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

the vaccinated population because of the influence of the bias.

mortality rates by vaccination status (unvaccinated, 1 dose or 2

This article explains this important issue, “healthy vaccineedoses 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 deaths are mainly【1】Healthy vaccinee effect and frailty-exclusion bias

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 well as

underestimation of harm [2-5].

that of non-COVID-19 deaths were reported.[8] Among them,Distortion of results or yielding results different from the

non-COVID-19 death was the main focus of this analysis,truth is called “bias” in epidemiology. Causes of such a bias

Mortality rate of non-COVID-19 deaths may increase if

are shown in details in another article in this issue.

COVID-19 vaccines are harmful. It may also increase

MED CHECK

Aug. 2022/ Vol.9 No.24 ・ Page 25

Review
when COVID-19 deaths are classified as non-Figure 1: Method for estimation of age-adjusted mortality rate in 2021

COVID-19 deaths. However, it would not be
reduced by the vaccines. Therefore, this article
focuses on the mortality rates of non-COVID-19
deaths.
(3) Monthly age-adjusted mortality rate is used
Monthly age-adjusted mortality rates in theunvaccinated and the 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

rates (y = -6.3552x + 13776) is extended to meet the year 2021 atin the UK was very low from April to June. As explained

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

fact that during this period in the UK, mortality rates of non-Page 26 ・ MED CHECK

Aug. 2022/ Vol.9 No.24

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

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 theoriginal figures, are used in this analysis. The number of COVID-19 deaths was very small from April to June 2021.

COVID-19 deaths increased in the unvaccinated and 21 days

deaths, such as other infections, heart diseases and cancers,

or later after the 1st dose.

while they can increase these illnesses as adverse reactions.
Therefore, if the mortality rate of non-COVID-19 deaths(3) Age-adjusted mortality rate of non-COVID-19 deathsin the unvaccinated is higher than the 2021 estimated age-

COVID-19 vaccines are believed to be effective in reducing

adjusted mortality rate, the increase can be attributed to theonset and aggravation of COVID-19 (infection caused byincrease due to the effect of frailty-exclusion bias (healthy

SARS-CoV2), and thus reduce deaths. Its efficacy on reducing

vaccinee effect).

onset and aggravation is proven by RCTs.
However, they are not supposed to reduce non-COVID-19

In addition, if the mortality rate of non-COVID-19 deaths inthe vaccinated is lower than the 2021 estimated age-adjusted

Figure 3: Non-COVID-19 deaths in unvaccinated population

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

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Aug. 2022/ Vol.9 No.24 ・ Page 27

Review
Figure 4: non-COVID-19 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.

mortality rate, the reduction can be attributed to the reduction

2) Mortality rates of non-COVID-19 deaths after thedue to the healthy vaccinee effect (frailty-exclusion bias).

second and third doses

The source of data used for this analysis is Office for
National Statistics Dataset [8].

Fig.4 shows the following:
A. age-adjusted mortality rates of non-COVID-19 deaths
after the second and third doses and the 2021 estimated age-1) The mortality rate of non-COVID-19 deaths in theadjusted mortality rate as reference, andunvaccinated (F.igure 3)

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

Figure 3 shows the following:

adjusted mortality rate (1.0).

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

In the beginning of the immunization program, the mortality

deaths and the 2021 estimated age-adjusted mortality rate asrate of non-COVID-19 deaths in those who had received

reference, andsecond dose was 0.2-fold (one-fifth) of the estimated mortality

B. mortality rate ratio (risk ratio) of unvaccinated population

rate (Note 2). In other words, they were 5 times healthier than

to the 2021 estimated age-adjusted mortality rate as reference

the general population.

(1.0).

Mortality rates in the unvaccinated 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 deaths within 20 days of the

December, 2021. The average mortality rate ratio was 1.77

second dose (0.25) and that of 21 days or later after the second dosethrough the year 2021, and 1.9 between April and June,(0.15). Details of statistical testing is omitted here, but it is certain thatwhen the mortality rate of COVID-19 was extremely low.

they are statistically significant.

During the period from mid-March to the end of June, excess

This tendency is consistent with the fact that the mortality

mortality was almost minus according to OWID [9]. Thisrate ratio at the initial stage of introduction of booster shotsmeans that higher mortality rate of unvaccinated in this period

which began in September 2021 was 0.2 (mortality rate waswas not affected by the excess death due to potential SARS-

0.2-fold).

CoV-2 infection.

It can be said that people who received the first vaccination

This is because many frail people might have avoided
vaccination. In other words, it was the result of frailtyexclusion bias.
Page 28 ・ MED CHECK

early, and especially those who could receive second or
booster vaccination were originally very healthy.
Mortality rates of non-COVID-19 deaths are markedly

Aug. 2022/ Vol.9 No.24

Figure 5: non-COVID-19 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).

low at the early stage after the second and third dose. This isexactly the effect of healthy vaccinee effect.

3) Mortality rate of non-COVID-19 deaths after first dose
Figure 5 shows the following:

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

A. age-adjusted mortality rates of non-COVID-19 deaths afterin September, mortality rates drastically increased especiallythe first dose and the 2021 estimated age-adjusted mortality

in those who died 21 days or later after the second dose. Thisrate 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.

At the initial stage of immunization program, the mortality
rate after the first dose was lower than the estimated mortality

Figure 6: Mortality rate of non-COVID-19 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 deaths (summary)rate. The mortality ratio within 20 days of the first vaccination
was 0.62. This suggests that the vaccinees were healthy until
this point.

the estimated mortality rates.
People who had received the first dose were relatively
healthy. Among them, some died without receiving the second

However, the mortality rate ratio at 21 days or later after
the first dose increased to 1.05. Usually the second dose isdose. It can be inferred that the additional deaths to theestimated mortality rate might be caused by the vaccines.

administered 21 days after the first dose. At this point, it ishighly likely that those who could not receive the second dose4) Mortality rate of non-COVID-19 death comparing by

had had health problems after the first dose.

number of doses

This tendency became especially evident between May to
July 2021, when there were very few COVID-19 deaths. The

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

mortality rates increased to as high as 5.4-fold to 6.8-fold ofFigure 8: Summary of trend in mortality rates of COVID-19 death, non-COVID-19 deaths, and all-cause mortality rates

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Aug. 2022/ Vol.9 No.24

5) Mortadlity rate ratio of non-COVID-19 deaths (by the
number of doses)

Figure 7 shows mortality rate ratio of non-COVID-19 deaths
to the 2021 estimated age-adjusted mortality rate (1.0) by
the number of doses. Mortality rate ratios of non-COVID-19
deaths by the number of doses shown in the Figure 7 are theaverage of mortality ratios within 20 days and 21 days or later
after vaccination.
People who were vaccinated with the first dose were
supposed to be healthier than unvaccinated people at theinitial stage of the immunization program. However, as thevaccination was promoted, high-risk people began to receive
vaccination. Among such people, there might have been many
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
after the second vaccination since the administration of
booster shots began.
6) Non-COVID-19 mortality rates ratio in ever vaccinatedIn the ever vaccinated, age standardised non-COVID-19
mortality rate (/100,000 person-years) in January 2021 was
564.7 (95% CI: 540.8 to 588.6) and the mortality rate ratio tothe expected mortality rate in 2021 (932.1/1001000 person
years) was 0.61.
According to the analysis (see p34-38 of this issue) using
the disclosed data by Dagan et al [9], healthy vaccinee effectis the most prominent (odds ratio is the least) at the vaccinatedday (day 1) and the effect became less prominent (odds ratio
increased) as days passed over 1 to 2 weeks. It seems that theseverer the symptoms, the higher this tendency.
For example, for symptomatic COVID-19, the ratio of OR
on day 1 (0.40) to OR during day 8 to day 14 (1.02) was 0.39
(95% CI: 0.30 to 0.50). For hospitalised COVID-19, the ratioof ORs (day 1-3/day 8-14=0.12/0.68) was 0.17 (95%CI: 0.04
to 0.78).
Hence, non-COVID-19 mortality rate ratio at the day of
vaccination (day 1) may be far lower than 0.61. If the ratioof ORs for symptomatic COVID-19 (0.39) or hospitalised
COVID-19 (0.17) is used, OR of non-COVID-19 death atthe day of vaccination may be estimated as 0.24 or 0.10
respectively.
7) Mortality rates of COVID-19 death, non-COVID-19
deaths, and all-cause mortality rate (by the number of doses)
Finally, trend in mortality rates of COVID-19 death,
non-COVID-19 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-

COVID-19 deaths. Similar influence can be observed in
mortality rates of COVID-19, and thus all-cause mortality
rates, in which the former and the latter are combined.
Mrtality rates of COVID-19 in the vaccinated seem to bemarkedly lower than that in the unvaccinated. However, it
should be noted that the mortality rates in the unvaccinatedare overestimated by about 2 times, and the mortality rates inthose who received 2 doses are underestimated by one-fifth.
(4) Mortality rate ratio of vaccinated to unvaccinated
In order to estimate the magnitude of healthy vaccinee effectin the observational studies, mortality rate ratio of the SARSCoV-2 vaccinated to the unvaccinated for COVID-19 related
death and non-COVID-19 death is calculated by month. In
the beginning of the immunization program (January andFebruary 2021), non-COVID-19 mortality rate ratio of those
who died 21 days or later after receiving the second dose to
the unvaccinated was 0.11 (95%CI: 0.08 to 0.14) and 0.13
(95%CI: 0.10 to 0.17). These indicates that healthy vaccinee
effect may work to lower the apparent risk of death fromCOVID-19 too and may increase the apparent effectiveness of
the SARS-Cov2 vaccine.
Harm of vaccine may offset the healthy-vaccinee effect as thepost-vaccination period increases. Hence the non-COVID-19
mortality rate ratio at the beginning of immunization programis suitable as the indicator of healthy-vaccinee effect.
COVID-19-related mortality rate ratio of those who hadreceived the second dose to the unvaccinated was 0.02
(95%CI: 0.01 to 0.04), which means apparent vaccine
effectiveness is 98% (95%CI: 96 to 99%). This mortality
rate ratio should be adjusted by the healthy vaccinee effect toavoid the bias.
Dividing the COVID-19-related mortality rate ratio of
0.020 by the non-COVID-19 mortality rate ratio of 0.11
yields a healthy vaccinee effect-adjusted COVID-19-related

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Aug. 2022/ Vol.9 No.24 ・ Page 31

mortality rate ratio of 0.18 (95%CI: 0.09 to 0.37) and vaccine
effectiveness of 82% (95%CI: 63 to 91%).
These may be considered to be closer to the true COVID19-related mortality rate ratio and vaccine effectiveness.

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"(in Japanese) https://www.npojip.org/sokuho/211228.html
3) MedCheck Editorial Team. Resuming HPV vaccination is very dangerous. Med Check

Conclusion

in English 2022: 8(23): 3-10

The mortality rate of non-COVID-19 deaths, whichhttps://www.npojip.org/english/MedCheck/Med%20Check%20TIp-23-2022-04.pdf
4) MedCheck Editorial Team. Symptoms after HPV vaccine: typical "frailty exclusion

vaccine does not reduce, was 0.2-fold of the expectedbias" in Nagoya City study. Med Check in English 2016: 2(5): 18-21

age-adjusted mortality rate in full vaccinated. It was 1.8-

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

fold in the unvaccinated, and 2.6-fold in those who had

Supplement for MedCheck No92 (In Japanese):https://www.npojip.org/chk_tip/2020No92-furoku.pdf6) Office for National statistics, Dataset：Deaths registered in England and Wales

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 unvaccinated 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 deaths. These indicate robust healthyvaccinee effect with SARS-CoV2 vaccine.

Page 32 ・ MED CHECK

https://www.npojip.org/english/MedCheck/Med%20Check-TIP%2005-08-08.pdf

Aug. 2022/ Vol.9 No.24

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/deathsbyvaccinationstatusengland9) 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):1412-1423.
doi: 10.1056/NEJMoa2101765.PMID: 33626250

NEWS
Imbalance 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.

MED CHECK

Aug. 2022/ Vol.9 No.24 ・ Page 33

Review

Why does 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.

on the Omicron variant [2-4] also suggest that the SARS-Introduction

CoV-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

Page 34 ・ MED CHECK

Aug. 2022/ Vol.9 No.24

recommend vaccination.

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, asymptomatic SARS-CoV-2

this discrepancy may be because observational studies do notinfection, symptomatic COVID-19, COVID-19 hospitalisation,

take “healthy vaccinee effect” (p 24 of this issue) into account.

severe COVID-19 and death due to COVID-19)from the day ofThis article presents the results of an analysis ofvaccination (day 1) to day 44.

epidemiological study from Israel: although the vaccine does

The daily incidence rates of event (/100,000 person-days

not work on the day of vaccination, the results show that the(pd)) comparing the vaccinated and the unvaccinated for 1

vaccinee’s incidences of asymptomatic infection, symptomatic

week after the first inoculation are shown in the Figure 1

infection, hospitalisation, severe disease and death were(asymptomatic SARS-CoV-2 infection: Figure 1 A and symptomatic

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

Covid-19: Figure 1 B).

will explain how these data were obtained from the original
paper and will discuss what these mean.

Incidence rates are lower in the vaccinated group thanthe unvaccinated group on day 1 especially of symptomatic
Covid-19.

Israel survey

Incidence rates of asymptomatic infection (/100,000

A nation-wide cohort study to evaluate the effectiveness ofpd) were 14 and 22 for the vaccinated and unvaccinatedthe SARS-CoV-2 vaccine was conducted in Israel [8]. Aboutgroups, respectively (difference is 8/100,000 pd), while those

600,000 people each were selected from vaccinated andof symptomatic COVID-19 were 15 and 38, respectively

unvaccinated population during the period from 20 December(difference is 23/100,000 pd). These indicate that vaccinated2021 to 1 February 2021. The vaccine effectiveness wasgroup has lower risk of SARS-CoV-2 infection.

assessed by SARS-CoV-2 infection at day 7 or later after
the second dose of vaccine, and it was 92% for documented

Risk increases until second week

infections, 94% for symptomatic COVID-19, 87% for

In the unvaccinated population, incidence rate (/100,000 pd)

hospitalised COVID-19, and 92% for severe COVID-19.

is almost consistent at around 25 for asymptomatic infection

Effectiveness for death was reportedly not assessed.

and 40 for symptomatic COVID-19.
In the vaccinated population, incidence is the lowest on day

Fewer illnesses from the day of inoculation
In the supplementary material of the report, precise life

1 and the difference is the largest on day 1. It increased andalmost reached the incidence of the unvaccinated on day 5

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].

MED CHECK

Aug. 2022/ Vol.9 No.24 ・ Page 35

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].

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

infection was 0.91 (0.83, 1.00) and that of the second week

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

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

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

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

exceeded unvaccinated population on day 7 (47 and 46,

respectively (Figure 2B).

difference was –1/100,000 pd) (Figure 1 B).

Estimation of odds ratio on day 1 for
Odds ratios of COVID-19 by time from first
inoculation by severity

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

Figure 2 shows odds ratios (ORs) of the vaccinated to the

COVID-19 or other severer COVID-19 patients. In theunvaccinated by time (days) from the first inoculation of

unvaccinated population, hospitalisation occurred from day

vaccine, by severity of SARS-CoV-2 infection:

1, but in the vaccinated population, hospitalisation did not

A. asymptomatic infection,

occur until day 3. Severe COVID-19 occur from day 3 inB. symptomatic COVID-19,

the unvaccinated, while it did not occur until day 6 in the

C. hospitalised COVID-19,

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

D. Severe COVID-19 and

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

E. 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

unvaccinated), OR cannot be calculated. Therefore, OR for theand reached 1.34 (1.05,1.70) for asymptomatic infection andhospitalised, severe cases and death due to COVID-19 on day

1.03 (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

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Aug. 2022/ Vol.9 No.24

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(HPd1)=OR(HPd1-7)×(OR(SYd1)/OR(SYd1-7)） (1)hospitalized COVID-19, severe COVID-19 and death due toOR(SVd1)=OR(SVd1-7)×(OR(SYd1)/OR(SYd1-7)） (2)

COVID-19 are 0.62, 0.40, 0.27, 0.18 and 0.13, respectively

OR(D d1)= OR(D d1-14)×(OR(SVd1)/OR(SVd1-14)(Figure 3).

(3)(1) OR of hospitalisation on day 1 (OR(HPd1)) is estimated

These data do not indicate the effectiveness of vaccine,by multiplying the OR of hospitalisation during day 1-7

but if this is described in terms of “vaccine effectiveness”,(OR(HPd1-7)) by the ratio of OR for symptomatic COVID-19

asymptomatic infections were reduced by 38%, symptomaticon day 1 (OR(SYd1)) to that of day 1-7 (OR(SYd1-7)).

infections by 60%, hospitalization by 73%, sever COVID-19
by 82%, and death due to COVID-19 by 87%.

(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.

epidemiological study which ignored “healthy vaccinee
effect”.

Moreover, the OR decreased as the symptom became severer:
OR for asymptomatic infection, symptomatic COVID-19,
MED CHECK

Aug. 2022/ Vol.9 No.24 ・ Page 37

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:10.1101/2021.12.30.21268565
6) Hansen CH, Schelde AB, Moustsen-Helm IR, et al. Vaccine effectivenessagainst SARS-CoV-2 infection with the omicron or delta variants following a twodose or booster BNT162b2 or mRNA-1273 vaccination series: A Danish cohort
study. medRxiv. 2022. doi:10.1101/2021.12.20.21267966 24
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9)Med Check editorial team. Web MedCheck No 205 (Aug 30) Why vaccine looks likeeffective to prevent severe Covid-19？-Another evidence of Healthy vaccinee effect.

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Editor-in-Chief: HAMA, Rokuro (MD)
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