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Volume 6

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Editorial
Sin of Being Deceived
Urgent Recommendations
Five Don'ts to Prevent COVID-19 and Death(Part 2)Five Do's to Prevent COVID-19 and Death
CONTENTS （April 3, 2020, Vol. 6, No. 17）
Editorial
Sin of Being Deceived

18

Urgent Recommendations
Five Don’ts to prevent COVID-19 and death (Part 2)
3. Don't use Tamiflu and Xofluza
4. Avoid ACE2 enhancers and (hidden) immunosuppressants
5. Don't sit up late at night. Lack of sleep is the strongest stress
impairing your immunity
Five Do's to prevent COVID-19 and death

19

30

MED CHECK

April 2020/ Vol.6 No.17 ・ Page 17

M
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Editorial

HECK

Sin of Being Deceived
Translated from the Editorial in Med Check(in Japanese) Nov 2019 ; 19 (123) ahead of print,

Do you know about Mansaku Itami, aJapanese film director and screenwriter? He
is Juzo Itami’s father, a Japanese movie actor
and director (The Funeral, A Taxing Woman) .
He died of tuberculosis in 1946, a year after
the end of the WWII. The title of this article
is taken from his essay "The Problem of War
Criminals".
After the world war II, the majority of theJapanese were trying to escape from their
responsibilities by justifying themselves thatthey had participated in the desperate war“because they had been deceived”. However,Itami said that being deceived is sin in itself,
pointing out that no dictionary had said “those
who were deceived are innocent”. He also said
that people were deceived not only because ofa lack of knowledge, but also of weak will.
Med-Check No.85 and No.86 criticize theJapanese Hypertension Guidelines 2019.
Physicians who have lost ability to thinkcritically and logically and have no faith areeasily deceived into believing in the guideline.
They prescribe expensive hypertensives,often leading to polypharmacy. In the wordsof Itami, it can be said that they are sinners. .
Remember the Diovan Scandal. Many doctors
were misled by the fake papers, prescribed
Diovan and contributed to the total sale of $1 billion per year. They are probably thinking
that they were just deceived.
However, doctors are professionals. If they
had read the fake papers critically with evena little skepticism, they would not have been

Page 18 ・ MED CHECK

April 2020/ Vol.6 No.17

fooled. Dr. Yoshiki Yui, Kyoto University, is theexample (see ref Concerns about the Jikei Heart
Study. Lancet 2012:379(9824) e48 and Med
Check in English No15).

Itami also said if people were not concerned
about the fact that they had been deceived,
they would be deceived again and again in
the future. If this applies to the world ofphysicians, if they do not mind that they weremisled in the Diovan incidence, they would
probably be repeatedly deceived.
If physicians who were deceived deeply
reflect on themselves, they would not trust
the Japanese Hypertension Guidelines
2019 created by the Japanese Society ofHypertension, which has not learnt any lessons
from the Diovan case. Instead, they would referto guidelines created by organizations without
conflicts of interest, such as National Instituteof Health and Care Excellence (NICE).
When people find out that they havehypertension through medical examination,
they simply take medicines prescribed by theirdoctors. To put it strictly, it can be said thatthese “patients” are guilty of being fooled.
When you buy something expensive like a
car or a house, you would research online orby reading books. Because whether to take a
medicine or not is about your or your family's
health, you should research more than when
you do shopping. It takes little effort to find areliable source of information with no conflictof interest, such as Med-Check.
To be deceived is sin in itself.

Urgent
Urgent Recommendations
Recommendations
Five Don’ts to prevent COVID-19 and death(Part 2)
Translated from Med-Check News No.185 (March 23 2020)
Med Check Editorial TeamMed Check in English No16 discussed two of the five Don’ts to prevent novel corona virus infection (COVID-19) anddeath. This article is for the remaining three Don’ts.
Before we get into the main subject, let's take a look at the world trend related to the antipyretic and corticosteroid use
discussed in Med Check in English No16.
Keywords:
COVID-19, ibuprofen, NSAIDs, paracetamol, corticosteroid, SARS-CoV, ACE, ACE2, ACE-I, ARB, immunosuppressants, sleeping pills,
glitazones hidden-immunosuppressantsFrench Health Minister: Avoid NSAIDs for COVID-19
The Guardian reported on March 13 that the Frenchalready contains warnings that their anti-inflammatory
effects may hide the symptoms of a worsening infection” [5].

health minister, Olivier Véran tweeted “The taking ofanti-inflammatories [ibuprofen, cortisone … ] could be a

However, a lot of epidemiologic studies and infectedfactor in aggravating the infection. In case of fever, takeanimal studies provide evidence that NSAIDs increaseparacetamol. If you are already taking anti-inflammatory

mortality and so do corticosteroids (see Med Check in

drugs, ask your doctor’s advice.” [1]. A similar statement

English No16), but WHO and EMA rarely mention thesewas made by the UK health authorities [2]. Thesestudies. In particular, they never mention the infected

were also reported in Japan [3] and the information

animal studies showing increased mortality without

seems to be spreading. Med Check thinks the advice is

exception.

basically good. , buAcetaminophen (paracetamol), which

Some researchers criticized the ideas of French

is recommended to use instead, is better than NSAIDs

minister or UK health authorities [6], but few have

and/or corticosteroid, but unfortunately inappropriate in

criticized them by showing evidence. Even whensome situations as we described in Med Check in English

evidence is presented, it is not strong enough to deny

No16.

the harm of NSAIDs. For example, Prof. Little (Primary

The World Health Organization (WHO) recommended

Care Research, University of Southampton) referred toon March 17 that people suffering from COVID-19

some studies, including practical randomized studies

symptoms to avoid taking ibuprofen [4]. But soon after

conducted by them. It is a small survey with participantsthat (as of March 22) , they updated their statement

less than 1,000 people and has no power to detect rarethat they did not recommend avoiding ibuprofen forcomplication of encephalopathy. He criticized French

COVID-19 symptoms [4].

minister based on such an inadequate research and

The European Medicine Agency (EMA) also questioned

pointed out methodological problems in observational

the scientific basis for ibuprofen regulation and saidstudies. He says “The observational evidence is always“patients and healthcare professionals can continue

difficult to interpret due to so called protopathic bias/

using NSAIDs” [5]. However, the EMA has acknowledged

confounding by indication (i.e. were the NSAIDs prescribedthat infection due to chickenpox (varicella) and someat an early stage of the complications developing and so thebacterial infections could be made worse by these

NSAIDs use reflects the complications or a more severe illness

medicines (NSAIDs including ibuprofen and ketoprofen).

rather than causing it)”

They also say “The product information of many NSAIDs

However, meta-analysis results of three case-control
MED CHECK

April 2020/ Vol.6 No.17 ・ Page 19

studies with least bias among 10 studies he referred

In addition, they never quote the fact that mortality ofshowed that use of NSAIDs such as ibuprofen is related

infected animals is increased by use of NSAIDs and/orwith increased severe infections by 4 to 6 times [8].

corticosteroids as reported in Med Check News No. 184.

Here is the summary of 5 Don’ts
1. Do not use antipyretics to lower fever. Human body can endure fever at 40-41℃. Because viruses are weak
to heat, lowering fever with antipyretics will lead to regrowth of the viruses. In particular, non-steroidal antiinflammatory drugs (NSAIDs) should be avoided, because they also weaken your defense system. Acetaminophen(paracetamol) is basically harmful, as well.

2. Do not use corticosteroids for the same reasons. Its use in the early phase of infection induce higher mortality.
3. Do not use Tamiflu and Xofluza as they suppress immunity.
4. Avoid ACE inhibitor and ARB (angiotensin II receptor blocker) as possible,because they increase
ACE2, an enzyme counteracting angiotensin II which acts as a main receptor for SARS-CoV-2 to infecthuman. Apart from anticancer drugs, corticosteroids and overt immunosuppressants used for collagendiseases etc., there are many other drugs that reduce your immunity (hidden immunosuppressants).
They include antihypertensive drugs especially ARBs and calcium antagonists, sleeping pills,
anxiolytics, cholesterol lowering agents, antidiabetics (glitazons, DPP-4 inhibitors, GLP-1 agonists)
and PPIs etc. They should be avoided unless they are essential.
5. Do not sit up late at night. A lack of sleep can be the biggest cause of stress that impairs your immunity.

3. Do not use Tamiflu or Xofluza for fever
Regarding Tamiflu and Xofluza, please read, the latest

3-1. What will happen if doctors diagnose influenza
without test?

information on Med Check in English No 15 (Dec. 2019)

In this flu season, flu was not very prevalent due tohttps://www.npojip.org/english/MedCheck/Med%20Check%20Tip-1

the unusually warm winter. However, a case has been

5-2019-12-29.pdf

confirmed in which a medical doctor who conductedwhich includes two papers:

a rapid testing for a patient suspected influenza was

1. Tamiflu: Deaths after Abnormal Behaviour among

infected with a novel coronavirus (SARS-CoV-2 orTeenagers Revisited: Probably related to the removal of

COVID-19 virus), because the patient was found infected

contraindications

with SARS-CV-2 later. Therefore, the Japan Medical

2. High Risk of Death from Tamiflu and Xofluza: Serious

Association recommended member doctors against

toxicity necessitating suspension of its use

testing even in case with suspected flu and recommended

And others in Med Check in English

diagnosis based on the clinical symptoms [8].

https://www.npojip.org/english/MedCheck/medchecktip.html:

This measure may be unavoidable and permissible

including:under the current situation where protective equipment

3. Cochrane team criticises the ECDC experts' draft

for infection prevention is lacking and the risk ofadvice on oseltamivir use:

infection will increase for doctors in collecting samples

https://www.npojip.org/english/MedCheck/Med%20Check-and for subsequent other patients.

TIP%2004-04-05.pdf(Apr. 2016)

However, the initial symptoms of the COVID-19 are

4. Critical comments to ECDC by Cochrane team.

very similar to those of flu. In China, Tamiflu was used as

https://www.npojip.org/english/MedCheck/Suppl% 20Critical%

an anti-influenza agent in about 90% or more patients at

20comments% 20to% 20ECDC% 20by% 20Cochrane% 20team.pdf

the beginning of the epidemic [9,10]

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April 2020/ Vol.6 No.17

What happened with these influenza viruses

3-2. Tamiflu might be prescribed to patients with
COVID-19
Of course, especially in Japan, Tamiflu, Xofluza or

and RS viruses, will happen naturally with the
COVID-19

other antivirals will be prescribed to patients with
COVID-19 if diagnosed influenza.

Do not use Tamiflu and other NIs as it makethe COVID-19 more severe

However, they have no effect on COVID-19. Will they
make COVID-19 worse?

3-4.No worries: Flu, COVID-19 will be better without
drugs
As described in the previous section, neuraminidase

3-3. Neuraminidase inhibitors such as Tamiflu
suppress immunity

inhibitors, such as Tamiflu, do not reduce the virus but

Influenza virus has an enzyme called neuraminidase.

reduce oniy symptoms as they reduce cytokines which

Tamiflu, which is still commonly used as anti-influenza

have actions to destroy virus. They simply prevent thevirus agents, are called "neuraminidase inhibitors (NIs)"

body from fighting the virus.

because it interfere with the action of this enzyme of thevirus.
Inhalers such as Relenza (zanamivir) and Inavir

Because anybody has strength to fight against viral
infection with their own defense system, drugs are notnecessary. They rather interfere the recovery.

(laninamivir) or an injection (Rapiacta or peramivir) also

belong to the group of "neuraminidase inhibitors (NIs)".

Even when you are infected with flu, nothing should befearedMany people including many physicians believe thatneuraminidase inhibitors (NIs) are effective to treat

Take this opportunity to develop a habit of not using
anti-influenza virus agents.

influenza, because they can decrease influenza virus. But
this belief is not supported with evidence.

3-5. Xofluza is more toxic than Tamiflu

On the contrary, “neuraminidase” is also found in cells

Xofluza is the newest anti-influenza virus agent

throughout the body of animals including humans. It

introduced in the clinical setting in Japan. It definitely

is an essential enzyme to keep cells healthy. When you

reduces influenza virus unlike Tamiflu or Relenza.

take Tamiflu, neuraminidase in your body (“endogenous

However, it produce resistant virus frequently. Moreoverneuraminidase” in medical term) is also inhibited, andit seems that it could inhibit important human enzymes.

immune function will be inhibited. Tamiflu reduce

In addition, since intra-intestinal concentration

cytokines which is induced to fight influenza virus. Hence

becomes high, intestinal mucosal cell function may

symptoms seem lighter, but the healing may be delayed.

be first weakened; subsequently water absorption is

It has also been confirmed in animals and humans

interfered, leading to diarrhea. Next, the regenerationthat clinical dose of Tamiflu reduces IgA antibodies ofof intestinal mucosal cells is inhibited causing injuries,

the mucosa in the nose and other respiratory tract forbleeding with melena. In addition, intestinal bacteria

protecting against influenza infection to one-fifth of

can enter the blood stream through injured mucosal

control (those without Tamiflu).

membranes and be translocated throughout the body,

There is a virus that causes severe respiratory

causing severe systemic infections (bacteremia and sepsis).

infections in infants called the respiratory syncytial

During the last influenza season (2018/19) , 4.27

virus (RS virus). This virus has no neuraminidase. Micemillion patients with influenza were prescribed withchallenged by RSV and administration with a clinically

Xofluza. Total 37 death cases were reported by doctors

compatible dose of Tamiflu showed symptom-relieving

who suspected these deaths may be related to the drug.

effects (decreased weight loss). However, virus increased

Mortality rate is at least 1 in 120,000. For those over 60

in the lung of mice.

years of age, mortality rate was 1 in 80,000. There wereThese are detailed in a review article on “ Theno reports of deaths among 3 million inhaler users, suchmechanisms of delayed onset type adverse reactions to

as Relenza and Inavir.

oseltamivir” [11]. It is also translated into Japanese [12].

.
MED CHECK

April 2020/ Vol.6 No.17 ・ Page 21

The novel coronavirus is transmitted not only fromsmoking followed by inflammatory reactions to repair.

the respiratory tract such as the lungs, but also from

They increase angiotensin II (Ang II), a substance thatthe mouth and enters the gastrointestinal tract. If theincreases blood pressure. At the same time, an enzyme

intestine is injured with Xofluza, intestinal mucosa iscalled ACE2 also increases in order to counteract Ang II.

easily infected with novel coronaviruses. As described in

ARBs (ang iotensin II receptor blo cker) and ACE

detail in the next section, the enzyme called ACE2, which(angiotensin converting enzyme) inhibitors further increaseacts as a receptor of novel CoV will increase where theACE2. In addition ARB has immunosuppressive action.

tissue is injured. It infects the intestinal mucosal cells,

Hypertension itself increases the risk of COVID-19 but

leading to translocation into the blood stream, leading to

drugs in addition worsen COVID-19. Actos, an agent forviremia. It infects various organs of the body attaching

diabetes (glitazones) also increases ACE2.

ACE2 as the receptor which is present throughout thebody, leading to multi-organ failures.

Apart from anticancer drugs, corticosteroids andovert immunosuppressants used for collagen diseases
etc, there are many other drugs that reduce yourDo not use Xofluza because it also makes theimmunity (hidden immunosuppressants) . They include

COVID-19 more severe

antihypertensive drugs especially ARBs and calcium

No worries again: Flu, COVID-19 will be better without

antagonists, sleeping pills, anxiolytics, cholesterol
lowering agents, antidiabetics (glitazons, DPP-4 inhibitors,

drugs.
Without Xofluza, you will recover faster overall. Of
course, even if you are infected with the novel CoV, it isbest to wait to recover naturally.

GLP-1 agonists) and PPIs etc. They should be avoided

unless they are essential.
Stop taking cholesterol-lowering agents at any time. Itis very safe to discontinue them. However, you should

4. There are many other drugs you
should avoid

stop some agents carefully. For example, if you want to

Summary

doctor.

stop sleeping pills or corticosteroids, please consult yourThe novel coronavirus (CoV) enters the cell withan enzyme called ACE2 as a receptor. This enzyme is4-1. The elderly is more susceptible to COVID-19 andfound on the surface of almost all cells in the bodymore easily deteriorated

and increases when the body is injured by sustained
excessive stress.

There were 3711 passengers and crew members on
the Diamond Princess. Because the population was inWhile influenza virus does not infect anything otherclose contact, all were tested, and the proportion ofthan the respiratory tract, Novel CoV infects the cells of

infected people and mortality were examined by age andthe intestine, translocates into the blood stream, goesby the presence or absence of symptoms (Figures 1-A andaround the body, and infects the cells throughout the

1-B).

body.

With a little exception of under 20 years of age, theIt is known that children and adolescents are lesshigher the age, the higher the percentage of positive

likely to be infected or become seriously ill, and that

PCR testing in both symptomatic and asymptomatic

elderly people, especially those aged 70 and older, areindividuals. Of all 3711 persons aboard of all ages, 712

more susceptible to infection and illness, and are more

were positive including asymptomatic as of March 29,

likely to become severely ill. In particular, patients withand the infection rate was 19.2% overall. Roughly, itchronic respiratory disease, stroke, high blood pressure,indicates that about 20% of the population, including

diabetes, and/or heart disease are known to be 3 to 8

asymptomatic individuals, may have been infected.

times more likely to be severely ill than those without.
Smoking also increases the risk by about 3-folds.

4-2.Chronic illness increases severity by 3-8 times

People with such chronic diseases or smokers have

Many reports point out that chronic illnesses are

tissues injured by the sustained stress or directly by

the risk factors which aggravate COVID-19 severe orPage 22 ・ MED CHECK

April 2020/ Vol.6 No.17

Figure 1: Percentage of PCR positive among people on Diamond Princess by age and by symptoms.
A: By age divided into 3 classes

Percentage of PCR positive for SARS-CoV-2 is higher in older people: more pronounced in asymptomatic individuals. Overall approximately 20 % of
all populations may be infected. Data for all ages* and mortality are based on the data on March 29, while others are those on Feb 20.
Figure was made by Med Check editorial team using data from ref [13-15].

B. By age every 10 years

This figure (1-B) shows a little exception that children tend to have a higher percent positive. Although the number is small and the 95% confidence
limit is wide, it may be due to the higher activity of children. Plot using data from Ref [13, 14]

MED CHECK

April 2020/ Vol.6 No.17 ・ Page 23

increase mortality. So far, weFigure 2: Chronic diseases make illness worse or increase death from COVID-19

meta-analysed the data forthe risk of comorbidity fromthe six reports [9,10,16-19]
up to March 10.
These reports comparedpatients who wereadmitted to ICU with those
who were not [9,10,18],
severe cases with nonsevere cases [16], or nonsurvivors with survivors[16,17,19]. Combined odds
ratio was 3.75 (95 % CI:2.73,* By fixed effect (Mantel-Haenszel, Robins-Breslow-Greenland)

5.19)(Figure 2).

The Table shows the results of meta-analysis forvarious chronic diseases and smoking. Among them,
the risk of stroke is particularly high. Is it related to thenumber of receptors in the brain?
Anyway, note that these odds ratio were derived
from the comparison of hospitalized patients andbody using an enzyme called angiotensin converting
enzyme-2 (ACE2). .
As we have seen in the previous section, elderly people
are more susceptible to COVID-19, especially those withchronic diseases. These may be deeply related. Let’s
explain how they are related.

not comparison with non-hospitalized mild cases. If

The first thing you need to know is that ACE2 is ancomparison were conducted between severe or deceased

important enzyme on the cell surface of all tissues

patients with non-admitted mild cases, the odds ratio

throughout the body, including the gut, lungs, brain,

may be much higher.

liver, kidney, and heart [20-23] (Figure 3) .
ACE2 is most commonly found in the small and large

4-3. Virus enters injured tissues attaching ACE2

intestines, but is found on the cell surface of organs(1) SARS-CoV-2 attach ACE2 to enter the body tothroughout the body, such as the lungs, kidneys, heart,systemic disseminationand liver. Furthermore, among leukocytes, ACE2 is

Not only the novel coronavirus (SARS-CoV-2 or
COVID-19 virus) [20-22] and SARS-CoV that emerged in2003 [23] but also non-SARS-CoV [24] infect the humanpresent in granulocytes and lymphocytes that are
significantly involved in the immune response.
For example, small intestine or colon is the organs with

Table: COVID-19 will be worsened with various chronic diseases and smoking

the highest expression of ACE2.
This may be because these organs
are vulnerable to injuries with a lotof bacteria inside. ACE2 modulates
innate immunity and influences thecomposition of the gut microbiota[23].
SARS-CoV-2 migrates into theblood, is distributed throughout the* Fixed effect by conditional maximum likelihood. Data from Huang[9], Wang[10], Zhang[16], Yang[17],body, and could infect every cell ofGuan[18] and Zhou [19] were meta-analysed.

the body [22, 25] (Figure 4).

Note the higher odds ratio of stroke/cerebrovascular diseases. Smoking is also one of the risk factors.
Note also that these are the results of comparison of all admitted patients. If comparison were conducted
between severe or deceased patients with non-admitted patients, the odds ratio may be higher.

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April 2020/ Vol.6 No.17

SARS-CoV-2 could enter into thebrain not only through the routeFigure 3: ACE2 is present in almost all cells of various organs

Expression of ACE2 in human tissues. Data represent Consensus Normalized eXpression levels for 55 tissue types and 6 blood cell types obtained fromThe Human Protein Atlas (www.proteinatlas.org). Cited from Ref. [20] with little modified by Med Check editorial team. ACE2 is expressed on all surfacesof cells throughout the body and increases when tissue is injured. In this data, the expression of ACE2 in the lung appears to be low, but in anotherdocument [21], the expression in the lung is about one third of the large intestine.

via the blood but also directly through the nose [22]cerebral infarction. If ischemia derived from persistent(Figure 4).

excessive stress affects your brain dopaminergic nerve,
it can cause inflammation in the dopaminergic system(2) Persistent stress with a lack of sleep injure your bodyleading to depression.

Excessive stress contracts blood vessels and increases
blood pressure, leading to poor supply of blood withoxygen. This situation is called "ischemia". If ischemia
continues, the tissue will be damaged.

(3) ACE2 increases when the body is injured
Stress causes a person excited and vasoactive
angiotensin II which is converted from inactive

The injured tissues made during daytime have to beangiotensin I by angiotensin converting enzyme (ACE)repaired while sleeping at night. However, if the injury

increases. This angiotensin II works towards making

during day time is serious and if you don’t sleep longwounds on the body. Our body is well-equippedenough to repair wounds, injured tissue remains evenand brakes to prevent injury induced by excessivein the morning. If these situations continue, wounds

angiotensin II. An enzyme called ACE2 is required towill build up in weak areas of your body, and themake the braking substance (Figure 5). The substanceinflammatory response will
gradually increase, manifesting

Figure 4: SARS-CoV-2 enters into the blood and infects cells throughout the body.

as a disease.
Eczema/dermatitis may be
the results of injured skin due
to the ischemia derived frompersistent excessive stress.
Injuries in the bronchi could
lead to asthma and chronic
obstructive respiratory disease(COPD). The same may be true

for colon leading to ulcerative
colitis, and for arteries toarteriosclerosis, hypertension,
myocardial infarction andCited from Ref. [22] and modified by Med Check Editorial team.

MED CHECK

April 2020/ Vol.6 No.17 ・ Page 25

Figure5: Inflammatory response differently affected by ARB or ACE-I

acting as a brake is called "angiotensin 1-7".

hypertension tends to cause intravascular injury due

In addition, when blood pressure becomes high, blood

to “shear stress” [26], and the antihypertensive drugs

flow becomes faster, and inner surface of the blood

including ACE inhibitor and angiotensin II receptor

vessel have pulsatile shear stress (PSS) . Experiments

blocker (ARB) further increase ACE2 [27,28].

have shown that PSS increases ACE2 as a compensatory

Patients with type 1 diabetes and/or with coronary

response to maintain normal function of cells inside theartery disease had more ACE2 than those without [28].

blood vessels [26].

Also, among diabetics, those who take ACE inhibitors or

The main reason why old people rarely infected and

ARBs also had higher ACE2 than those who do not.

deteriorated with non-SARS-CoVs even though they
have many receptors (ACE2), may be because they had(5) Young people getting ill with COVID-19 have diseases

been frequently exposed with non-SARS-CoVs in their

If you have complications, ACE2 increases in diseased

childhood and have immunity to these viruses. However,organs, making it more susceptible to infection and more

SARS-CoV-2 is a completely new virus and old people

severe condition with COVID-19.

have no immunity to protect against it and they alreadyOn the other hand, young adults without complications

have a lot of receptors (ACE2) in their body, while

relatively less intected whether asymptomatic or

younger people have far less ACE2.

symptomatic. It is probably because ACE2 has notincreased significantly in young adults. Young person(4) ACE inhibitors and ARBs further increase ACE2
The liver of the rats that was administered carbon

having comorbidity may be susceptible to COVID-19 andcould get severely ill.

tetrachloride expressed more ACE2 than that of control

Therefore, those who have no complications do not

rats. If rats were pretreated with ACE inhibitors ACE2

need to be overly afraid of the COVID-19 if they are

increased further compared to rats not receiving ACE

aware of what has been said in this article so far.

inhibitors [27].

Of course, in order to avoid infection as much as

Usually mild hypertension does not lead to a serious
disease, but SARS-CoV can be as severe as diabetes
or heart disease (see Table). This is due to the fact that
Page 26 ・ MED CHECK

April 2020/ Vol.6 No.17

possible, actions to avoid “closed environment”, “crowd”
and “close contact” are essential.

4-4. The other Drugs that worsen COVID-19

tuberclosis. These trials should be stopped, because they
may increase severity and death from COVID-19.

Substances that reduce inflammation, such as
nonsteroidal anti-inflammatory drugs (NSAIDs) and(2) Beware of the many "hidden immunosuppressants"

corticosteroids, exacerbate any infectious diseases

Although, we can easily understand that anticancer

because they diminish the body's function to protect

agents, corticosteroids and overt "immunosuppressants"

against pathogens, such as viruses.

have immunosuppressive effects, we should be aware of

These agents apparently relieve symptoms transiently,
because they stop defense system including fever andmany other agents that suppress immunity even if they
are not classified as immunosuppressants.

induction of cytokines to fight pathogens. However,For more information, please refer to each issue ofin the meanwhile, the virus goes deeper into the

Med Check (Med Check TIP) in English, Encyclopedia ofbody and multiplies, causing the body to emit moreDrugs You Should avoid(in Japanese), Encyclopedia ofcytokines and symptoms become more severe. The"How to Stop Drugs" (in Japanese).

so-called cytokine storm (storm of cytokines) blows.
NSAIDs including ibuprofen and aspirin typically induce

1) Antihypertensive agents:

cytokine storm injuring endothelial cells all over the

1. ARB is a typical hidden immunosuppressants (seebody. It induces acute respiratory distress syndrome

above). See Figure 5 for a detailed explanation of how(ARDS), encephalopathy with liver damage or necrotizing

immunity is suppressed and how its mechanism differs

encephalopathy with multi-organ failures.

from ACE inhibitors [32].
2. Calcium antagonists suppress the influx of calcium

Lancet's article [29], quoted by the WHO [4] toions into the cells of vascular smooth muscle, dilate blood

recommend against ibuprofen in COVID-19 cited thevessels and lower blood pressure. However, it is notreason why ibuprofen increases ACE2. However, only aonly smooth muscle that activates cells due to calcium

single paper was found for the evidence basis on this [30].

influx. Many immune cells are also activated by calcium

Moreover, ibuprofen was not used for infectious diseases

influx, such as the action of pancreatic beta-cells thatin the study[30]. Therefore, causing cytokine storms

secrete insulin and mast cells and lymphocytes that playthrough hypothermia and anti-inflammatory effects may

an important role in immunity [33]. Therefore, calcium

be far more important than increasing AEC2 for the

antagonists not only dilate blood vessels and lower bloodmechanisms in which NSAIDs worsen COVID-19.

pressure, but also slow down insulin secretion to develop
and exacerbate diabetes. It suppresses immunity, making(1) Immunosuppressants worsen infections

it more susceptible to infections and cancer.

It is clear that anticancer drugs, corticosteroids andimmunosuppressants used for rheumatism and collagendisease exacerbates COVID-19 because they block
defense response to the virus.

2) Cholesterol-lowering agents [34-36]
All cholesterol-lowering agents suppress immunity.
People with high cholesterol level live longer with better

People with atopic dermatitis may not only use

activity of daily life than people with low cholesterol. This

topical steroids, but also immunosuppressants such as

is because cholesterol is essential for the function of all

tacrolimus (Protopic) ointments. These are very harmful.

cells, including immune cells. Do not lower cholesterol.
In particular, the most commonly used statins not only

We noticed that many clinical trials testing strong

lower cholesterol, but also suppress immunity throughimmune suppressants are conducted for treatment

function other than lowering cholesterol. Do not use

to reduce severity and/or mortality from COVID-19

them. If you are taking cholesterol lowering drugs, you[31]. These include methylprednisolone, tocilizumab

can stop them at any time. There is no inconvenience orand baricitinib. They are planned mainly in Italy. But

harmful effect for you even if you stop them.

these immunosuppressants increase infection including3) Sleeping pills and anxiolytics [37-39]
MED CHECK

April 2020/ Vol.6 No.17 ・ Page 27

In addition to the most commonly usedbenzodiazepines (Note) such as Ambien (zolpidem) ,relatively new melatonin derivative ramelteon (trade name
Rozerem) and the orexin receptor antagonist suvorexant

5. Don’ t sit up late at night. A lack ofsleep is the biggest cause of stress andreduces immunity(Bersomura) also suppress immunity. The quality ofWhen you have a fever, you have to take a rest. Whensleep obtained with sleeping pills is poor, increasing

you are not infected, it is important that you exercise

depression, infectious diseases and cancer, and thus

moderately during the day time and take enough sleep

shortening life expectancy. Don't use them. However, in

at night to avoid stress and repair injuries that you hadorder to discontinue, you must be patient and decrease it

during the day time. A lack of sleep is the greatest stress.

very slowly. The same is true for anxiolytics.

A lack of sleep at night with excessive stress during
day time, sympathetic nerves are activated and immunity

Note: The so-called “non-benzodiazepines” are classified
based on the structure. Because "non-benzodiazepines"or “z-drugs” also act as benzodiazepine receptor agonist,same as the structurally classified benzodiazepines, “MedCheck" classify them (z-drugs) as benzodiazepines in termsof mechanism of action.

4) hypoglycemic agent [40-43]
・ Actos (glitazone): Carcinogenic and increases ACE2.
https://www.npojip.org/english/MedCheck/Med%20Check-is suppressed. As a result, blood vessels in various partsof the body contract, resulting in an inadequate supply ofoxygen and nutrients. This is "ischemia", which can cause
tissue injuries. ACE2 increases in the injured tissues
through which SARS-CoV invades your body easily,
making your body susceptible to disease and severe
condition.
When you sleep, sympathetic nerves are calmed. On
the contrary, parasympathetic nerves become active

TIP%2005-08-08.pdf

and activate immunity. Injured tissues are healed by

・ DPP4 inhibitor

immunity while sleeping enough at night, before you get

・ GLP-1 receptor agonist (Injection)

up in the morning. However, if the stress during the day

・ SGLT-2 inhibitors

is too strong or the sleep time is too short, the injuries

They are also carcinogenic and exacerbate infectious

induced during the day time will not be cured and will

diseases.

be carried over to the next day, accumulate and become
inflamed in various parts of the body. This is the disease.

5) Drugs for asthma [44]The cause is common in many diseases even if they・Inhaled corticosteroids: Fluticasone is a very strong

occur in different parts of the body.

immunosuppressant.
・Beta agonists (salmeterol, formoterol, salbutamol,

Don't sit up late at night! A lack of sleep is theetc.) suppress function of immune cells suppressing

biggest stress.

inflammation. Minimum required should be used.

Don't have sleep debt, the main cause of
immune suppression6) Gastric acid suppressant (also frequently used for reflux
esophagitis etc.) [45]・ Proton pump inhibitors (PPI)・H2 blockers7) Others: Fluoride [46] also suppress immunity.

Page 28 ・ MED CHECK

April 2020/ Vol.6 No.17

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Biochem Biophys Res Commun. 2020 Mar 10. pii: S0006-291X(20)30440-X.
PMID:32169277

1) https://www.theguardian.com/world/2020/mar/14/anti-inflammatory-drugsmay-aggravate-coronavirus-infection2) https://www.dailymail.co.uk/news/article-8121255/NHS-no-longer-advisescoronavirus-patients-ibuprofen.html
3) https://news.yahoo.co.jp/byline/saorii/20200315-00167830/
4) https://www.sciencealert.com/who-recommends-to-avoid-taking-ibuprofen-forcovid-19-symptoms5) https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-antiinflammatories-covid-196) https://www.sciencemediacentre.org/expert-reaction-to-reports-that-the-frenchhealth-minister-recommended-use-of-paracetamol-for-fever-from-covid-19-ratherthan-ibuprofen-or-cortisone/7) Hama R unpublished data8) https://www.mixonline.jp/tabid55.html?artid=68919
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32031570
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14) https://cmmid.github.io/topics/covid19/severity/diamond_cruise_cfr_estimates.html
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Jan;37(1):e1-6. doi: 10.1111/j.1440-1681.2009.05302.x. Epub 2009 Sep 28.
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10.1159/000375362. Epub 2015 Apr 15. PMID: 25896805
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Check 2019: 5: (15): 38-43 https://www.npojip.org/english/MedCheck/Med% 20C
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34) Ravnskov U, Diamond DM, Hama R, Hamazaki T, Ogushi Y, Okuyama H et al.
Lack of an association or an inverse association between low-density-lipoproteincholesterol and mortality in the elderly: a systematic review. BMJ Open. 2016 Jun
12;6(6):e010401. PMID:27292972
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16) Zhang JJ, Dong X, Cao YY, Yuan YD et al Clinical characteristics of 140 patients36) Ravnskov U, de Lorgeril M, Diamond DM, Hama R, Hamazaki T et al. LDL-C does

infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Feb 19. doi: 10.1111/

not cause cardiovascular disease: a comprehensive review of the current literature.

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Belsomra): A substance that causes narcolepsy and cataplexy. Is it a “medicine”?

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Med Check 2017: 3: (9): 29-33.

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cohort study. Lancet. 2020 Mar 11. pii: S0140-6736(20)30566-3. doi: 10.1016/

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S0140-6736(20)30566-3. [Epub ahead of print] Erratum in: Lancet. 2020 Mar 12;

2016: 2: (5):22-25. https://www.npojip.org/english/MedCheck/Med% 20Check-

PMID:32171076
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TIP% 2005-08-08.pdf41) Med Check team. SGLT-2 inhibitors: Unacceptable products Med Check 2015: 1: (1):3-4

of 2019-nCoV. Biochem Biophys Res Commun. 2020 Feb 17. pii: S0006-

https://www.npojip.org/english/MedCheck/Med% 20Check-TIP% 2001-4-25.pdf

291X(20)30339-9. doi: 10.1016/j.bbrc.2020.02.071. PMID:32081428

42) Med Check team. Critical assessment of Diabetic Guidelines. Med Check 2019:with reference from “Human protein atlas”: https://www.proteinatlas.org/

5(13):10-15.

ENSG00000130234-ACE2/tissue

https://www.npojip.org/english/MedCheck/Med% 20Check% 20Tip-13-2019-5-3.pdf21) Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, Li T, Chen Q. High expression of43) Med Check team. GLP-1 Agonists (liraglutide): No evidence of improving

ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci.

prognosis in patients with diabetes: Not recommended. Med Check 2016: 2

2020 Feb 24;12(1):8. doi: 10.1038/s41368-020-0074-x. PMID:32094336(6):36-42

22) Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targetinghttps://www.npojip.org/english/MedCheck/Med% 20Check-TIP% 2006-12-12.pdf

the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic44) Med Check team. Cardiovascular toxicity of beta agonist for asthma and COPD.

Mechanisms.
ACS Chem Neurosci. 2020 Mar 13. doi: 10.1021/acschemneuro.0c00122. [Epub

Med Check (in Japanese): 2020: 20 (88): 36-38. (in Japanese)45) Med Check team. Pneumonia caused by proton pump inhibitors (PPI) Med Checkahead of print]

2017: 3 (9):40-45

PMID: 32167747

Part 1:meta-analysis, Part 2:Critical appraisal of a study using prior event rate ratio23) Perlot T, Penninger JM. ACE2 - from the renin-angiotensin system to gut
microbiota and malnutrition. Microbes Infect. 2013 Nov;15(13):866-73. PMID:
23962453
24) Chang L, Yan Y, Wang L. Coronavirus Disease 2019: Coronaviruses and Blood
Safety.. Transfus Med Rev. 2020 Feb 21. pii: S0887-7963(20)30014-6. PMID:
32107119
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Isolation of Human Coronavirus 229E. Jpn J Infect Dis. 2016 Sep 21;69(5):452-4.
PMID:27357992
26) Song J, Hu B, Qu H, Wang L, Huang X, Li M, Zhang M Upregulation ofangiotensin converting enzyme 2 by shear stress reduced inflammation andadjustment method
https://www.npojip.org/english/MedCheck/Med% 20Check-TIP% 2009-12-27.pdf46) Hama R et al. Fluoridation of tap water increase cancer risk. The Informed
Prescriber 2002: 17 (8/9): 86-98 (in Japanese) https://www.npojip.org/fusso/tipfusso.html
47) Hama R. Benefit and harm of fluoridation of tap water. The Informed Prescriber
2004:19(8/9): 82-91 (in Japanese)48) Hama R Don’t hungover injuries. Inflammation is the cause of all diseases andstress is the cause of inflammation.
Med Check No56 (in Japanese) https://www.npojip.org/contents/book/mag056.html
49) Hama R. Encyclopedia of "How to Stop Drugs" (in Japanese). Sangokan 2018proliferation in vascular endothelial cells.

MED CHECK

April 2020/ Vol.6 No.17 ・ Page 29

Urgent
Urgent Recommendations
Recommendations
Five Do’s to prevent COVID-19 and deathTranslated from Med-Check News No.185 (March 23 2020)
Med Check Editorial TeamThe ongoing epidemic of corona virus infectious disease (COVID-19) is disrupting our daily life. Controversial
information is prevailing. “Ibuprofen is harmful/safe” “The SARS-CoV-2 is/not vulnerable to high temperature.” “Drinking
hot water is/not effective.” True information is sometimes treated as false. As we wrote in the No 16 issue of Med Checkin English, we are trying to our best to meet such needs as much as possible. In this article, we rather focus on somepoints based on evidence which are widely misunderstood and will not discuss things which are commonly covered by
the media.

Five Do’s (summary)
1. Simple mask-wearing is effective. It reduced illness from SARS to one-third, and is more
effective than frequent hand-washing (>10/day) that halved it.
2. Mask-wearing is effective because SARS-CoV is vulnerable to high temperature with humidity. It
helps your nose and throat keep warm and moisturized.
3. When masks are not available, make it with cloths or handkerchief. They can be washed andused repeatedly.
4. Drink hot drinks such as “kuzuyu (drink made from arrowroot starch). Blowing on and sipping it
help warm the throat and the whole body.
5. Get moderate exercise during the day, and have enough sleep at night, but without sleeping
pills.

Keywords:
COVID-19, SARS, mask-wearing, hand washing, high temperature, humidity, Cochrane review, enough sleep, stress, ischemia

1. Simple mask-wearing is effective
The results of the Cochrane review [1] provide thea result for mask-wearing.
Overall odds ratio was 0.32 (95% confidence interval(95%CI): 0.26-0.39, p<0.00001). This suggests that simple

most reliable information as of today on the effect ofmask-wearing reduces the risk of onset to 32

mask-wearing. It can be accessed for free of charge.

result of 7 studies combined.

% as aDuring the SARS epidemic, the association between

With hand-washing for more than 10 times daily, odds

the onset of SARS and various preventive measures wereratio for infection with SARS was 0.54 (95% CI:0.44- 0.67,

examined. Jefferson et al [1] reviewed and meta-analyzed

p<0.00001) (Figure 1B). This suggests that it only halved

these studies. Odds of several interventions such as

the risk. Statistically, mask-wearing is more effective thanmask-wearing and hand-washing were compared inhand-washing, because upper limit of 95% CI for Mask

patients who developed SARS (cases) and those who did

wearing (0.39) is lower than the lower limit of 95 %CI fornot (controls) after matching sex and age. Figure 1 shows

hand washing (0.44).

Page 30 ・ MED CHECK

April 2020/ Vol.6 No.17

Figure1: Effect of physical intervention in SARS Prevention
A: Simple Mask-wearing

How to read the figure 1a above: The data in the top column is based on the report by Chan (2009). In people who did
not develop SARS, 541 of 657 persons were wearing masks while in those who developed SARS, only 59 out of 91 were
wearing masks. Odds ratio, which was a ratio between odds of mask users/non-users in people with SARS and odds ofmask users/non-users in people without SARS, was 0.40. This means that the risk of infection with SARS is reduced to
40% by wearing mask. In the next study by Lau (2004), odds ratio is 0.28 (93/237:388/272). This means that the risk ofinfection with SARS is reduced to 28% by wearing mask. Based on the combined data from 7 case-control studies (Total),mask-wearing reduced risk for SARS infection to 32% .

B: Hand washing (>10/day)

Jefferson T et al. Cochrane Database Syst Rev. 2011 Jul 6; Issue 7[1]Most experts emphasize the importance of hand-

N95 respirators are also effective in preventing thewashing. They say that mask-wearing is effective only

onset, and their preventive effect was apparently greaterin preventing the spread of virus from the infected

than that of simple masks. However, the difference wasthrough sneezing and cough, but not really effective innot statistically significant, because upper limit of 95%

preventing healthy people from being infected. They also

CI for N95 respirators (0.43) is higher than that for Mask

recommend disposing and changing masks frequently.

wearing (0.39). Rather, because N95 respirators, whose

We do not know why, but we have never heard themreferring to the result of the Cochrane’s review [1].

fiber is densely packed, tend to be uncomfortable andirritating to skin [1].
MED CHECK

April 2020/ Vol.6 No.17 ・ Page 31

The information from the World Health Organization(22-25℃ )and 33℃ , but the speed is slow. The majority(WHO) [2] is slightly different from that of Japaneseof the media labeled the information that “the virus die

experts. It announced that healthy people do not usuallyat 26-27 ℃ ”as false, claiming that if it is true, the virus

need to wear a mask, but when they have contact withshould die immediately after they enter human body, butpeople who are infected or suspected to be infected

they do not. However, as shown in Figure 2, even at thewith SARS-CoV-2, they should wear a mask. Although it

temperature of 38 ℃ , they do not die immediately. At

does not cite references, it can be said that the WHO hasroom temperature (22-25℃ ), at one to two days after theadmitted the preventive effect of mask-wearing whenstart, titre is reduced to almost 1/10, but it takes 2 to 3

personal contact with infected patients is involved.

weeks until they are totally lost.

２．Why mask is effective?
Higher temperature and humidity
Masks keep the nose and through warm andmoisturized.

Under low humidity environment, viral viability isdecreased at slower rate even at 38℃ (Figure 3). Viruses
survive for a long time under low humidity and low
temperature conditions.

At the time of writing this article, at 10 a.m. on March
5th, the ambient temperature was 9℃ .
RH took the temperature in his mouth just near his

This proves that keeping nose and throat warm andmoisturized is extremely important for preventing the
growth of viruses at the sites.

throat, and it was 22-23℃ without wearing a mask. Afterputting on a mask, he took the temperature again in the

Another experiment investigated how much surrogate

same way, and it was 32-33℃ . The difference was aboutviruses of SARSCoV, such as transmissible gastroenteritis

10℃ with and without wearing a mask.

virus (TGEV) and mouse hepatitis virus (MHV), survive on

Although he did not measure and compare thestainless steel[4](Figure 4).

moisture in his throat, it would probably be more than
95% with a mask. In winter, both temperature and

The result showed that the infectious viruses persisted

humidity are low. Especially in areas like Hokkaido,

for as long as 28 days at 4 ℃ and relative humidity (RH)

ambient temperature goes below 0℃ .

20%.
However, at 40℃ and RH 80%, the levels of the viruses

Figure 2 compares infectivity of SARS-CoV at different
temperature [3]. It gradually die at room temperature

were undetectable after only 6 hours, suggesting thatthey had actually been all inactivated.

Figure2: Effect of temperature on SARS-CoV viability

Cited from Chan Kh et al [3], modified and comments by Med Check team.

Page 32 ・ MED CHECK

April 2020/ Vol.6 No.17

At near room temperature(20℃ ) and at RH 20

Figure3: Reduction of SARS-CoV by different temperature and relative humidity% ,viruses decreased to 1/100
after 28 days, while they wereundetectable after 1 to 2 weeks
when RH was over 50%. This
coincides with the result shownin Figure 2 and Figure 3.
In other words, viruses areinactivated much more rapidly
at room temperature (26-27℃ )than at 4℃ and at RH 20%.

Therefore, the information“viruses die at 26-27 ℃ ”is not

Cited From Chan Kh et al. Adv Virol 2011;734690 [3]simply “wrong”. They just do
not die “immediately” under such a condition.

Mask-wearing keeps nose and throat moisturized(probably over 95%) and keeps the temperature at least

These explains why epidemic of SARS and COVID-19

at over 30℃ , and is effective. As mentioned earlier, thishave occurred in winter, when it is cold and dry.

is why even simple masks are effective. When infected,

Therefore, it might subside in Japan during rainy season,

high fever is expected, but it should not be lowered

when it is warm and humid. However, room temperatureespecially with medicines. This was discussed more inshould not be made too low by air conditioners.

detail in Med Check No 16.

Figure4: Reduction of viruses by different temperature and relative humidity

Cited From Casanova LM et al. Appl Environ Microbiol 2010; 76::2712-7 [4]MED CHECK

April 2020/ Vol.6 No.17 ・ Page 33

３． If masks are not available, use
handkerchief or hand-made masks. They
can be washed and used repeatedly.

When it is over 55 ℃ , it would be difficult to drink in
big galps. By drinking a hot drink slowly, it will warm
throat while passing. It takes time for kuzuyu (drink
made with arrowroot starch) to cool down. So prepare it

Mask shortage is lingering world widely. In order towith boiling water, and sip it while blowing on it. This

keep nose and throat warm, not only masks but also

warms and moisturizes throat and the whole body, andcovering mouth with handkerchief is very effective. You

also suppresses the growth of viruses which just entered

can find how to make masks with handkerchief at thethe throat. The most important measure for preventing

following website.

infection and onset is to keep the body warm including

https://news.nifty.com/article/domestic/society/12159-0303m040324/

nose and throat.

https://m.facebook.com/story.php?story_fbid=2828756543847418&id=

Hand-washing is also important, but hand-washing for５． Get moderate exercise during the
day and enough sleep at night, but do
not rely on sleeping pills.

more than 10 times a day is less effective than mask-

When you have fever, take a rest. When you are notwearing. Some experts recommend to frequently change

infected and healthy, get moderate exercise duringmasks in a day, but this would aggravate the shortage.

the day and have enough sleep at night to avoid

Moreover such an advice is unrealistic as they are notaccumulation of stress. A lack of sleep is the biggest

available in market.

cause of stress.

415021871887576

Even if a small amount of virus that may be on yourA lack of sleep with persistent excessive stresshands enters nose and mouth, if you can suppress its

activates sympathetic nerve and suppresses immunity,

growth in the body, the onset can be prevented. Masks

constricting vessels and impeding blood flow. Thiscan be washed and used repeatedly. When washedcondition is called ischemia, which injure tissue due torepeatedly, the metal part of masks might become rusty.

lack of oxygen and nutrition. As viruses easily enter fromIf so, drying them under the sun would also kill viruses

the injured tissue with excessive expression of a receptor

as they are weak to ultraviolet, and they can be usedenzyme ACE2, as shown in the previous article (Five Don’repeatedly. Spraying alcohol would also be effective in

ts Part 2), such a condition leads to COVID-19.

sterilizing masks.

At night, sympathetic nerves are calmed down,
and parasympathetic nerves become dominant. The

４．Sipping hot drink while blowing on it
helps warm throat and the whole body.

injuries created during the day are healed by morning

Some media report “if viruses really die at 26-27 ℃ ,However, if the stress during the day is too intense

they should die as they enter the body, but they do not.

and/or sleep hour is too short, the injuries cannot be

So this information is false, and drinking hot water ishealed during sleep, but is accumulated and develop

not effective, either”. However, this is totally based on

inflammation, causing disorder at various parts of themisunderstanding.

body [5,6]. This is how sickness is caused. Different

As mentioned in points 1 and 2 above, corona virus
and transmissible gastroenteric virus (TGEV), as wellby immunity which is activated during sleep at night.

people might develop disorder at different parts of thebody, but the cause is very similar.

as influenza virus, persist for a long time in a cold andMost patients who develop severe COVID have somedry environment. On the contrary, they are rapidly

kind of sickness at baseline. For instance, in those withinactivated at high humidity and temperature above

only hypertension, the disease is 2.3 times more likely to

38-40 ℃ , which is like the body temperature when we

become severe, and in those with diabetes and/or heart

have fever.

disease as well as with history of stroke, it is 3-5 times

The temperature of hot water which we can drink

more likely to become severe as shown in the previous

in big galps is probably more or less around 46-50 ℃ .

article (Five Don’ts Part 2). People with chronic illness

Page 34 ・ MED CHECK

April 2020/ Vol.6 No.17

have damaged tissue caused by excessive stress and/or

only in respiratory organs and does not enter blood nora lack of sleep, and inflammation to heal the injuries.

infect other parts of the body while the latter infect not

Viruses easily penetrate into the body from the woundonly infect respiratory cells byt also digestive system

or site of inflammation with excessive expression of aincluding mouth and gut and enter into blood, circulating

receptor enzyme ACE2, leading to be infected easily andthe whole body and infecting cells all over the body.

aggravated.

Most children and the youth are usually healthy andNovel corona virus is more contagious than SARS,

have less injured tissues. That is why they are less likely

which spread in 2003, but these two viruses are very

to be infected or develop severe infection. Young people

similar. SARS-CoV enters the body by binding to ACE2

with chronic illness are infected more easily and might

receptors that are present in any cells. One of the most

become severer than without. Majority of people do notprominant differences between influenza virus and SARS-

need to be so afraid of novel corona virus as long as they

CoV or SARS-CoV-2 is that the flu virus infects cells

follow the recommendations we described in this series.

Five Don’ts
1. Do not use antipyretics to lower fever. Human body can endure fever at 40-41℃ . Because viruses are
weak to heat, lowering fever with antipyretics will lead to regrowth of the viruses. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided, because they also weaken yourdefense system. Acetaminophen (paracetamol) is basically harmful, as well.
2. Do not use corticosteroids for the same reason. Its use in the early phase of infection induce higher
mortality.
3. Do not use Tamiflu and Xofluza as they suppress immunity.
4. Avoid ACE inhibitor and ARB (angiotensin II receptor blocker) as possible, because they increase
ACE2, an enzyme counteracting angiotensin II which acts as a main receptor for SARS-CoV-2 to infecthuman. Apart from anticancer drugs, corticosteroids and overt immunosuppressants used for collagendiseases etc., there are many other drugs that reduce your immunity (hidden immunosuppressants).
They include antihypertensive drugs especially ARBs and calcium antagonists, sleeping pills,
anxiolytics, cholesterol lowering agents, antidiabetics (glitazons, DPP-4 inhibitors, GLP-1 agonists)
and PPIs etc. They should be avoided unless they are essential.
5. Do not sit up late at night. A lack of sleep can be the biggest cause of stress that impairs yourimmunity.

Five Do’s
1. Simple mask-wearing is effective. It reduced illness from SARS to one-third, and is more effective
than frequent hand-washing (>10/day) that halved it.
2. Mask-wearing is effective because SARS-CoV is vulnerable to high temperature with humidity. It helps
your nose and throat keep warm and moisturized.
3. When masks are not available, make it with cloths or handkerchief. They can be washed and used
repeatedly.
4. Drink hot drinks such as “kuzuyu (drink made from arrowroot starch). Blowing on and sipping it help
warm the throat and the whole body.
5. Get moderate exercise during the day, and have enough sleep at night, but without sleeping pills.

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April 2020/ Vol.6 No.17 ・ Page 35

References
1) Jefferson T et al. Physical interventions to interrupt or reduce the spread of
respiratory viruses. Cochrane Database Syst Rev. 2011 Jul 6; Issue 7. No:
CD006207. PMID: 21735402
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993921/
2) WHO Coronavirus disease (COVID-19) advice for the public
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-forpublic
When and how to use masks
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-forpublic/when-and-how-to-use-masks
3) Chan KH, Peiris JS, Lam SY, Poon LL, Yuen KY, Seto WH. The Effects ofTemperature and Relative Humidity on the Viability of the SARS Coronavirus. Adv
Virol 2011;734690. PMID:22312351
4) Casanova LM, Jeon S, Rutala WA, Weber DJ, Sobsey MD. Effects of air temperatureand relative humidity on coronavirus survival on surfaces. Appl Environ Microbiol
2010;76::2712–2717 PMID: 20228108
5) Hama R. Do not have hungover injuries! All illness are caused by inflammation
which are cased by excessive stress Med Check No56：https://www.npojip.org/
contents/book/mag056.html
6) Hama R. Encyclopedia for stopping drugs. Sangokan Publshing Co. Ltd. 2018https://bookmeter.com/books/11662184

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2020

Vol.6

No.17

Editor-in-Chief: HAMA, Rokuro (MD)
Deputy Editor: KIMOTO, Yasusuke (MD); TANIDA, Noritoshi (MD)Managing Editor: SAKAGUCHI, Keiko
Editorial Staff: NAKANISHI,Takeaki(Pharmacist); TAKANO, Yoshihiko(MD[pediatrician]/Pharmacist) ; YANAGI, Motokazu (MD); YASUDA, Yoshinobu(Pharmacist)
Translators: NAKAMURA, Akari ; TAKAMACHI, Koji

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April 2020/ Vol.6 No.17

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