Vol.11 (July 2020, 7) BCG and polio vaccines / Clinical trials in the UK: dexamethasone / Masks in hot and humid weather / etc.

[1] BCG and polio vaccines: Cell-mediated immunity

(1) A paper on the correlation between the BCG vaccination system and the new coronavirus

The COVID-100 death rate per million people is 2.1 in countries with BCG vaccination systems and 42.6 in those without.
Among countries that do not currently have a BCG vaccination system, the highest rate was 146.5 people in countries that have never had a vaccination system in the past, while the rate was 34.0 people in countries that had a system in the past.
It seems that there is a relationship between the presence or absence of a BCG vaccination system and the COVID-19 mortality rate.

(Figure 1) Differences in mortality rates according to BCG vaccination status

(Source) T. National policies for paediatric universal BCG vaccination were associated with decreased mortality due to COVID-19 [published online ahead of print, 2020 Jun 18]. Respirology. 2020;10.1111/resp.13885. doi:10.1111/resp. 13885
https://onlinelibrary.wiley.com/doi/full/10.1111/resp.13885

(2) The Japanese BCG strain is the oldest and most potent.

This is a paper by Professor Miyasaka of Osaka University, which I also mentioned in my previous article.
The BCG vaccine used today was first produced at the Institut Pasteur in Paris in 1921, and the original vaccine strain was then distributed to various laboratories around the world and cultivated in each country.

(Figure 2) History and genetics of BCG vaccine strains

This paper scores the strength of each BCG vaccine strain's effectiveness in vaccinating children, and shows that the type cultivated in Japan has the strongest effectiveness.

(Source) Is BCG vaccination causally related to reduced COVID‐19 mortality?
EMBO Mol Med (2020)12:e12661https://doi.org/10.15252/emmm.202012661
https://www.embopress.org/doi/full/10.15252/emmm.202012661

(3) Using polio vaccine instead of BCG to promote cell-mediated immunity

I have read papers about the low mortality rate of COVID-19 in countries that have BCG vaccination systems and the background to this (BCG strains), but that does not mean that people who have never received BCG should just get vaccinated now.
There is a paper that discusses the possibility of a "polio vaccine" as an alternative to BCG.

Vaccines include both attenuated (viruses whose toxicity has been sufficiently reduced) and inactivated (killed) vaccines.
These can induce neutralizing antibodies to acquire long-term immunity against specific pathogens, or they can activate cellular immunity to attack specific viruses.

It has become clear that live vaccines have the ability to activate natural immune mechanisms and create a broad-based barrier to protect against infection.
In particular, it may be possible to temporarily prevent COVID-19 infection by stimulating natural immunity with the live polio vaccine (OPV).

Because both polio and COVID-19 are positive-strand RNA viruses, it is expected that they will activate common innate immune pathways. There are many benefits to administering OPV.

• ①Safety has been thoroughly confirmed
• ②Since it is compatible with multiple virus types, it can be expected to stimulate immunity for a long period of time.
• 3) Inexpensive
• 4. Easy to administer
• ⑤ Abundant supply

One billion doses are produced each year and administered in more than 10 countries.
BCG is in limited supply, while OPV only requires a small amount from the polio eradication campaign to be diverted for clinical trials.
If it proves effective against COVID-19, it may be possible to increase production all at once.

OPV is safer than BCG.
BCG has a 1% side effect rate after vaccination. Side effects from OPV are extremely rare.
Vaccine-associated paralytic polio (VAPP) has an incidence of 300 in 1 million, mostly affecting immunocompromised children.
If administered properly, OPV is a safer choice than BCG.

(Source) Dr. Michiyuki Matsuzaki's explanatory material "SCIENCE Perspective: Can the Live Polio Vaccine Prevent COVID-19?"

(Original source) Can existing live vaccines prevent COVID-19?. Science. 2020;368(6496):1187‐1188.
https://science.sciencemag.org/content/368/6496/1187

[2] The Oxford University clinical trial "dexamethasone" and the effects of steroid treatment

In June, the results of a clinical trial led by the University of Oxford in the UK in which the common steroid dexamethasone was administered to 2000 patients with COVID-XNUMX (announcing that it was effective in reducing the mortality rate in the most severely ill patients) attracted worldwide attention and was widely reported in the media.
Please do not misunderstand. Taking dexamethasone on a regular basis does not mean that you will not be infected with the new coronavirus or that if you are infected, your condition will not become severe.
Taking steroids when you don't need them can even cause side effects.
In patients with rheumatoid arthritis, taking steroids increased the risk of developing severe symptoms, but in asthma, the risk of infection did not increase, possibly due to the use of inhaled steroids.
Steroid therapy should be administered carefully and based on a doctor's diagnosis.

(1) Clinical trials of dexamethasone have shown it has a life-saving effect on severely ill patients

Dexamethasone reduced mortality by 2% in patients requiring oxygen and by 35% in patients on ventilators.
No benefit was seen in milder patients who were not receiving oxygen or mechanical ventilation.

(Source) Nature News
Coronavirus breakthrough: dexamethasone is first drug shown to save lives [2020 Jun 16]. Nature. 2020;10.1038/d41586-020-01824-5. doi:10.1038/d41586-020-01824-5
https://www.nature.com/articles/d41586-020-01824-5

(2) Among rheumatoid arthritis patients, the number of hospitalizations increased in those taking 10 mg or more of steroids.

People with rheumatic diseases are thought to be at risk of serious infection with the new coronavirus, and a paper on this has been published.

A daily steroid dose of 1 mg or more was associated with an increased incidence of hospitalizations, whereas anti-TNF drugs were associated with a decreased incidence of hospitalizations.
Antirheumatic drugs and nonsteroidal anti-inflammatory drugs were not associated with an increased risk of hospitalization.

(Source) Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician- reported registry
Ann Rheum Dis 2020;79:859-866. doi:10.1136/annrheumdis-2020-217871
https://ard.bmj.com/content/79/7/859

(3) The prevalence of underlying bronchial asthma was significantly lower among people infected with the new coronavirus

A study of over 3 patients with COVID-8, conducted in eight regions across three countries (China, the United States, and Mexico), revealed the prevalence of COVID-17,000 comorbidity with asthma.

Compared to the prevalence of asthma in each region, it was found that the rate of people with underlying bronchial asthma was significantly lower among those infected with COVID-19.
Patients with severe COVID-19 infection were significantly more likely to have chronic obstructive pulmonary disease (COPD) and diabetes, but having bronchial asthma was not correlated with the severity of the disease.
It has been found that a cytokine related to allergic diseases (interleukin 13: IL-13) reduces the expression of a molecule (angiotensin-converting enzyme 2: ACE2) that the new coronavirus binds to when it invades epithelial cells.

(Figure 3)

■Of the 8 total COVID-17,485 patients reported from eight cities in China, the United States, and Mexico, the prevalence of bronchial asthma was 5.27%. The prevalence of bronchial asthma in the general population of the countries was 7.95%, which was significantly lower in the patient group.

■Among the total of 2,199 COVID-1,193 patients in China and the United States (1,006 mild cases and XNUMX severe cases), the proportion of patients with chronic obstructive pulmonary disease and diabetes was significantly higher among severe cases. There was no difference in the proportion of patients with bronchial asthma.

(Source) Kenji Matsumoto, and Hirohisa Saito. Does asthma affect morbidity or severity of Covid-19? Journal of Allergy and Clinical Immunology 2020
https://www.jacionline.org/article/S0091-6749(20)30736-3/fulltext

[3] Regarding masks during hot and humid seasons

Finally, I would like to introduce various papers on masks.
With summer approaching, many people are already feeling the heat and breathlessness of wearing masks, but at the same time, "wearing a mask correctly" is essential as a risk measure for contracting the new coronavirus.
This is the first summer since wearing a mask has become a must-have item in our new daily lives, and many new products have been released, but we recommend that you look for a mask that fits you well and can withstand high temperatures and humidity.

(1) Wearing a mask can reduce the risk of infection from a pre-symptomatic patient by more than half.

Research has also shown that wearing a mask reduces the risk of infection.

Between January 1 and March 23, 3 cases of COVID-1 were discovered in Taizhou City, Zhejiang Province (127 were returnees from Wuhan and 63 were city residents). A retrospective analysis was conducted on the contact histories of city residents who had community-acquired infection.
Those who wore masks were significantly less likely to become infected than those who did not (8.1% vs. 19.0%, p > 0.001).

(Figure 4) Comparison of the incidence of COVID-19 patients when wearing masks and when not wearing masks

(Source) Mask wearing in pre-symptomatic patients prevents SARS-CoV-2 transmission: An epidemiological analysis [2020 Jun 24]. Travel Med Infect Dis. 2020;101803. doi:10.1016/j.tmaid.2020.101803
https://www.sciencedirect.com/science/article/pii/S1477893920302994

(2) When doing walking-level exercise while wearing a mask, carbon dioxide may accumulate.

Masks have become an indispensable item, but you need to be careful how you use them.
In April, there were reports of several deaths among students in China who were exercising while wearing N4 masks.
A 2010 paper published a study on the effects of N95 masks on medical personnel.

Ten medical workers were asked to wear N10 masks and walk for one hour (at speeds of 95 km/h and 1 km/h). Arterial blood carbon dioxide increased to 2.7 torr (normal is 4) in 21- and 42-year-old subjects with no apparent illness.
Masks put a lot of strain on the heart and lungs: they fatigue the inhalation muscles, reduce oxygen intake and increase consumption, and cause carbon dioxide buildup as you rebreathe some of your exhaled air, increasing the risk of respiratory acidosis.

(Source) Physiological impact of the N95 filtering face respirator on healthcare workers Respir Care, 55 (5) (2010), pp. 569-577
https://pubmed.ncbi.nlm.nih.gov/20420727/

(3) Disposable masks are a source of microplastics

In addition, the increased use of masks is beginning to have an impact on the environment on a global scale.
No one has yet offered an "answer" to this, but the impact is being felt even in places like this, showing that we need to learn to use masks in the right way.

Disposable masks such as surgical masks are used to prevent infection with the new coronavirus, but most are made of non-woven fabric made from plastic fibers.
Discarded plastic fiber masks can become a major environmental problem.
Care must also be taken when disposing of nonwoven masks.

(Figure 5) Image of the environmental impact of increased mask usage

(Source) Covid-19 face masks: A potential source of microplastic fibers in the environment [2020 Jun 16]. Sci Total Environ. 2020;737:140279. doi:10.1016/j.scitotenv.2020.140279
https://www.sciencedirect.com/science/article/pii/S0048969720338006

(4) The inside of an N95 mask is a hot and humid environment.

In our new daily lives, we are being asked to learn how to wear masks properly.
As the paper states, it is hot and humid inside a mask, but the conditions improve (obviously) when the mask is removed.
If you are maintaining social distance and in a quiet environment (where no one is talking), temporarily removing your mask will not increase your risk of infection.

I wore an N95 quality 7-layer mask (3 inner layers of cloth mask, 1 bandana in the middle, and 3 outer layers of medical grade mask) for 6 hours from 24am onwards, and monitored the temperature (blue line: Fahrenheit) and humidity (brown line) inside the mask (graph). While wearing the mask, it was hot and humid at 37°C and 80% humidity. When I removed the mask, both the temperature and humidity plummeted.

(Figure 6) Environment inside the mask (temperature and relative humidity)

(Source) Living with in-mask micro-climate. Med Hypotheses. 2020;144:110010. doi:10.1016/j.mehy.2020.110010
https://www.sciencedirect.com/science/article/pii/S0306987720317138

(5) Cloth masks have a 100% leakage rate, while non-woven masks have a 50% leakage rate: Viruses enter through gaps

When it comes to wearing a mask properly, how you wear it is also important.
Although the extent to which a mask can protect against COVID-19 droplets varies depending on the size of the droplets that the virus adheres to, there is no better way to reduce the risk of infection through COVID-19 droplets than to wear a mask correctly.

　To what extent can cloth masks prevent airborne viruses? Associate Professor Onishi Kazunari (Environmental Epidemiology) of St. Luke's International University investigated the "leakage rate" of airborne particles that enter and exit through gaps between cloth masks and the face, and found it to be 100%. Even nonwoven masks that passed filter performance tests had a 100% leakage rate if worn improperly, but this dropped to around 50% when worn correctly. "The way you choose and wear a mask is important," he said.
Using a special device to check the adhesion of masks, the number of particles over 0 micrometers floating in the air and the number of particles in the gap between the mask and the face were measured and compared. In addition to cloth masks, nonwoven masks, and dust masks that meet standards such as N3, three different types of "Abenomask" (gauze masks) distributed by the government to every household were examined, all made from different materials. For nonwoven masks and dust masks, whose leakage rate varies depending on how they are worn, a comparison was made between wearing them normally and wearing them in a way that minimizes gaps, such as by fitting them correctly around the nose.
As a result, the leakage rate of cloth masks and gauze masks was 100%. The lowest leakage rate was 1% when dust masks were worn correctly, and 6% when worn normally. When non-woven masks were worn correctly, the leakage rate was 52% for types that had passed tests for the filtration performance of the filter, and 81% for types that had not. However, when worn normally, both types were 2%.

(Source) Asahi Shimbun Digital Naoya Ima July 2020, 7 6:16
https://news.yahoo.co.jp/articles/f5f03f1819ee4f639d01d9f810c72acced067b75

Masks developed by major electronics manufacturers and major clothing retailers have been widely reported, but other manufacturers are also working on developing various new masks.
In order to use masks properly and survive the hot and humid summer, it is important to choose and use masks carefully.

(6) Masks incorporating new technologies are appearing one after another

Although wearing a mask does not provide complete protection, masks incorporating new technologies are now appearing one after another.
Let me give you an example.

・Masks using antivirus technology from Swiss company Livingard
(GSI Creos)^{Note 1}

The company's anti-virus technology applies a positive charge to the surface of the fibers at a molecular level, so that bacteria are permanently destroyed upon contact.

・Yamamoto Chemical Industry makes mask covers for medical workers^{Note 2}

The medical equipment and composite material manufacturer has developed a mask made of synthetic rubber that is tightly sealed and virtually impermeable to moisture, sebum, and viruses. It can be reused for about one and a half to two years after washing with water or sanitizing with alcohol.
I actually tried using it while working at the clinic, and I felt that it fitted better than conventional masks and was easy to breathe through.

・"Copper fiber sheet" masks created by Gunma universities and local companies^{Note 3}

Noting that the survival time of the new coronavirus on copper surfaces is as short as four hours, the company has developed a mask cover that utilizes the copper fiber sheet that it had been developing for some time.

・Nanofiber mask with the same effectiveness as N95 masks: Yamashin Filter^{Note 4}

The company, which develops oil-straining filters used in factories, has used a previously acquired patent to develop a mask that can capture viruses and other microorganisms at the nano level.

The moves of each company as they continue to develop unique masks will remain a source of interest, but in order to get through the hot and humid summer, we should all be mindful of how we choose and use our masks carefully.

• Note 1: Reference https://www.nikkei.com/article/DGXLRSP536429_U0A620C2000000/
  https://prtimes.jp/main/html/rd/p/000000001.000060053.html
• Note 2: Reference https://www.nnn.co.jp/dainichi/news/200423/20200423028.html
• Note 3: Reference https://media.dglab.com/2020/05/19-gudi-01/
• Note 4: Reference https://dime.jp/genre/936355/