I am not a medical expert and this is just a hypothesis; taking BCG vaccination may strengthen immune to the novel coronavirus. If I were American/West European/Australian, I would take BCG vaccination now. Six reasons follow.



I declare that there is no conflict of interest for BCG vaccination but I have a big interest in stopping this pandemic. One of my businesses is an online tourism agency and its sales have dried up!





(Added on 4 Apr) The comment system does not work on this post anymore. Too many comments? For discussion purposes, I created Too many comments? For discussion purposes, I created a new post . Please leave a comment on the post below.



https://www.jsatonotes.com/2020/04/please-leave-comments-here-regarding.html





1) Scientists have started to work on this hypothesis

Can a century-old TB vaccine steel the immune system against the new coronavirus?

https://www.sciencemag.org/ news/2020/03/can-century-old- tb-vaccine-steel-immune- system-against-new-coronavirus

(Added on 9 Apr) They seem to use only BCG Denmark. I strongly recommend using BCG Japan/Russia in those clinical trials. You will understand after reading this post.

https://mobile.twitter.com/nigeltwitt/status/1244576788283457536



The Max Planck Institute (the best German science institution with 33 Novel Prize winners that developed BCG vaccine a century ago)

Immune boost against the coronavirus

https://www.mpg.de/14610776/ immune-boost-corona-virus

Some countries, the U.S. and Australia will start a trial to give BCG vaccine to healthcare workers.

https://foreignpolicy.com/2020/03/24/coronavirus-vaccine-health-care-workers-bcg/





2) If you look at the map displaying BCG vaccination policy by country, there seems to be a correlation to the speed of coronavirus spread and its spread among young people.



https://www.researchgate.net/ figure/Map-displaying-BCG- vaccination-policy-by-country- A-The-country-currently-has- universal_fig2_50892386 A: The country currently has universal BCG vaccination program.* B: The country used to recommend BCG vaccination for everyone, but currently does not. The year the country stopped it; Spain 1981, Germany 1998, UK and France 2005-2007 etc. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062527/ C: The country never had universal BCG vaccination programs.

* In Portugal the BCG vaccine was mandatory from 1965 to 2017. https://twitter.com/ruipalma79/status/1243304538469273600

The major correlations are; The spread speed is fast in Italy and western Europe and the U.S. while the spread speed among Russia, eastern European countries, and Asian countries except Wuhan city is slow.

In Asian countries, there are few young infected people or almost zero serious cases among young people. However, in western Europe and the U.S., there are cases among young people.**

In Western Europe, you can compare Italy vs Croatia, Spain vs Portugal***, UK vs Ireland, Sweden vs Norway, ex-West Germany vs ex-East Germany. In the former countries, BCG vaccine is not mandatory while in the latter countries, BCG vaccine is mandatory. Now, you can compare the U.S. and Mexico.

I live in Tokyo and Brisbane. Though the normal social distance is much longer and less crowded in Brisbane and the government policy is 10 times stricter, the spread speed is faster in Brisbane than in Tokyo. In Latin America, Ecuador is the only country that never had universal BCG vaccination programs and all the other countries have universal BCG vaccination programs according to the map above*. Total deaths per million, Ecuador: 2, Colombia: 0.08, Peru: 0.3, Brazil: 0.3.



* (Added on 5 Apr) A reader told me that Ecuador has its BCG program. However, it started in 1977. No strain information. (Added on 29 Apr) Another reader said that Ecuador started its universal BCG vaccination program in 2018. Reliable information with a source is welcomed.

https://www.jsatonotes.com/2020/04/please-leave-comments-here-regarding.html?showComment=1586045707606#c3278707554083878141

https://www.jsatonotes.com/2020/04/please-leave-comments-here-regarding.html?showComment=1588133504315#c8773910608298539454

According to According to http://www.bcgatlas.org/ , the start year for Columbia: 1960, Peru: 1945, Brazil: 1976. Brazil was late to introduce the program but it uses BCG Moreau.



(Added on 29 Mar)

A reader told me there is a pre-print article (not yet certified by peer review)

https://www.medrxiv.org/content/10.1101/2020.03.24.20042937v1



The article has this chart. I believe if we can adjust for the timing of coronavirus spread, the correlation would be even higher.



(Added on 10 Apr)

BCG vaccine contains an attenuated form of the bacteria (germ) that causes TB (I learned this in this April...). Then the prevalence of TB can correlate with COIVD-19. Below is the map of TB prevalence from WHO. You can easily see the correlation. I guess that the amount of BCG vaccine + TB prevalence is the key driver. Interestingly, Iran's TB prevalence is as low as western Europe. Immunologists' explanations are welcomed.



https://www.who.int/publications/10-year-review/tb/en/index1.html

https://twitter.com/takainou_0907/status/1247338851099504640



(Added on 30 Mar)

In the world map of the BCG vaccine policies above, Canada is in orange and categorized in C: The country never had universal BCG vaccination programs. However, if you look at Canada in http://www.bcgatlas.org/ it seems that Canada had a "routine" BCG vaccination program until 1960s-1970s (Please correct me if I read wrongly). This means people elder than 40s mostly vaccinated! This may be the reason why Canada has a low death rate compared with the U.S. And Canada used BCG Tokyo strain .



(Added on 14 Apr) Canada had used BCG Connaught, not Tokyo. Please check this post for the detail. And if you check the post below, please skip the next section grayed out.

https://www.jsatonotes.com/2020/04/the-bcg-hypothesis-age-group-comparison.html





One more weak fact. In Canada, people elder than the 60s had a BCG vaccine while people younger than 50s had not. Then, look at the age distribution of COVID-19 cases in Canada. Skew to people younger than the 50s?! But infection rate may not vary by age, only hospitalization/ICU/death rate may vary by age. I'm looking for that data and BCG vaccine penetration data by age group for Canada.







https://www.statista.com/statistics/1107149/covid19-cases-age-distribution-canada/



(Added on 6 Apr)

Ultra-Orthodox Jews are said to refuse BCG vaccination historically. In New York or Israel, huge spikes of COVID-19 (more than 40% of the community infected) are reported in the U ltra-Orthodox Jews communities. The articles say their pray style or lifestyle can be the causes but I believe this is because of lacking the BCG vaccine.

https://www.haaretz.com/us-news/.premium-as-coronavirus-spreads-these-u-s-jewish-communities-pray-they-re-not-next-1.8728042

https://time.com/5815426/israel-orthodox-jewish-coronavirus/



** I couldn't find good stats on this. Only anecdotal news stories. Eg. Greta Thunberg got infected by the novel coronavirus. Well, she is Swedish and born in 2003. Sweden stopped BCG vaccination in 1975. (Added on 13 Apr) Finally, I get a quantitative analysis of this! Please check this post.

https://www.jsatonotes.com/2020/04/the-bcg-hypothesis-age-group-comparison.html



*** Among West European countries that had/have universal BCG vaccination program, Spain and Portugal are (one of) the last countries introduced it in 1965. And Spain is (one of ) the first country to stop it in 1981 and Portugal stopped it in 2017. Portuguese elder than 55 may have a low BCG vaccination rate, which may result in a high death rate than the other western Europe, but probably better than Spain. 3) There are several strains of BCG vaccination and Japan/Russia strains may be the most effective against the novel coronavirus. This comment by Tiger Paw sounds most plausible regarding the country differences though the article itself is worthless. https://www.japantimes.co.jp/opinion/2020/03/21/commentary/japan-commentary/japan-still-coronavirus-outlier/#comment-4843977551

* The comment was deleted for some reason. The initial idea of this section attributes to Tiger Paw. If I hadn't read his comment, I would not know there are multiple types of BCG vaccine.

Soviet/Japan strains of BCG vaccination are old-type and similar while Western European stains are recent and different.



Below is a map of German states with confirmed coronavirus cases. You can see the difference between ex-East Germany and ex-West Germany. The density of the population doesn't explain this much difference. East Germany had used BCG S4-Jena* that is the second generation of BCG vaccinations and West Germany had used BCG Denmark that is the third generation of BCG vaccination and stopped its mandatory vaccination in 1998. The vaccination strains/policies may be the cause of the difference. (I added a table of BCG vaccination policy in Germany in the next post.)



* https://twitter.com/shirogoma_kinak/status/1247091133903024128

https://mra.asm.org/content/4/2/e00296-16.full













https://en.wikipedia.org/wiki/2020_coronavirus_pandemic_in_Germany

Then, look at the number of deaths by state. Summing up by ex-West Germany and ex-East Germany (excluding Berlin), the number of deaths per 100K of ex-West Germany states is 0.35 while ex-East Germany is 0.11 and Berlin is in between; 0.21 (as of 27 Mar).







https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Situationsberichte/2020-03-27-en.pdf?__blob=publicationFile

https://twitter.com/takainou_0907/status/1243754536138731521/photo/1

You can see this table updated on 4 Apr.

https://www.jsatonotes.com/2020/04/please-leave-comments-here-regarding.html

https://twitter.com/takainou_0907/status/1246684588287488000



(Added on 4 Apr) A reader did a fantastic analysis regarding ex-West/East Germany. He/she separated ex-West/East within Berlin and categorized regions by the population. Within Berlin, the deaths/per 0.1M population in ex-East is 0.24 while it in ex-West is 0.76. Three times different! This would be not only one of the critical evidence of this hypothesis but also counter-evidence of the other hypotheses such as virus mutation variation hypothesis or the virus arrival timing hypothesis, etc.

https://twitter.com/Iku42888817/status/1246368330409099265 https://twitter.com/Iku42888817/status/1247163231715508225

I obtained a map showing which strains are used in each country though this map maybe not perfectly correct.

https://twitter.com/io302/status/1243441971709894657 https://twitter.com/io302/status/1243441971709894657/photo/1

High-level impression; BCG Brazil, BCG Russia/Bulgaria, BCG Japan countries may immune to novel coronavirus. Countries that use more than one BCG vaccine strain look immune, too. BCG Brazil, BCG Russia/Bulgaria, BCG Japan are categorized in "I" and this may be the effective strain category.

Then, I looked into how BCG strains are categorized. I found the chart below. BCG Russia/Japan/Moreau(Brazil) is the first generation of the BCG vaccines.

In the same article, there is a table that shows the differences in each strain character. Though I don't understand any jargon in the first row, I can see there is quite a difference between BCG Tokyo/Moreau(Brazil)/Russia/Sweden and BCG Copenhagen(Denmark)/Glaxo/Pasteur/Tice. BCG Denmark is the common strain among Western Europe.

https://jata.or.jp/rit/rj/tenbo/48toida.pdf https://twitter.com/xcvbnm67890/status/1243723927907471361

(Added on 7 Apr) The number of living bacteria/ml is high in BCG Japan and Russia, and relatively low in BCG Brazil. This may be the cause that BCG Japan/Russia seems very effective against COVID-19. https://news.yahoo.co.jp/byline/kimuramasato/20200405-00171556/ https://www.jstage.jst.go.jp/article/kekkaku1923/62/2/62_2_51/_pdf

While Iraq uses the Japan strain*, Iran uses different strains. According to http://www.bcgatlas.org/ Iran had used its local (original?) BCG vaccine from 1947 to 1984 and madee it compulsory in 1984. This means elderly people in Iran have less BCG vaccinated and for those who had it had a local(original?) BCG vaccine. Please check and compare Iraq and Iran figures. You will be surprised to see how different they are. https://www.worldometers.info/coronavirus/ (Iran: 27 deaths per million, Iraq: 0.9 deaths per million as of 27 Mar; added) * Additional source is welcomed. The map above says it BCG Japan but http://www.bcgatlas.org/ does not have Iraq's strain info. I suspect Iraq uses a different strain. https://www.wjpls.org/admin/assets/article_issue/41072019/1564535230.pdf says that Iraq changed from the Denmark strain to the Japan strain but it doesn't tell when.

(Added on 25 Apr)

According to UNICEF's data, the percentage of live births who received BCG in Iran is 1980: 7, 1981: 6, 1982: 10, 1983: 10, 1984: 10, 1985: 79. Most Iranian who are elder than 36 years old were not BCG vaccinated.

https://data.unicef.org/resources/data_explorer/unicef_f/?ag=UNICEF&df=GLOBAL_DATAFLOW&ver=1.0&dq=IRN.IM_BCG..&startPeriod=1970&endPeriod=2018



In Asian countries, China uses a different local produced strain and Korea uses basically BCG Denmark but sometime BCG Japan. Taiwan uses the Japan strain (though the map shows a locally produced strain).

BCG Japan(Tokyo) looks working quite well against the novel coronavirus. 1) Japan, Thailand, Taiwan, Iraq, and Pakistan have used BCG Tokyo and all of them have low death rates though they are close to China or Iran. 2) And so far, it is not reported that any Japanese got severely infected or died in Italy or Western Europe. 3) In Japan, there are 1,349 cases reported, and 934 are Japanese and 415 are non-Japanese. Hmm, quite a high ratio of non-Japanese (as of 28 Mar). https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000164708_00001.html#kokunaihassei

(Added on 10 Apr) Below are the countries that have used the BCG Tokyo strain mostly and deaths per 1 million population. Pakistan and Iraq are next to Iran. Taiwan, Thailand, Japan had many Chinese visitors. The BCG Tokyo strain seems to be the most effective, more effective than BCG Russia.

Japan 0.8

Bangladesh 0.1

Pakistan 0.3

Iraq*** 2

Saudi Arabia* 1

Taiwan 0.2

Thailand 0.5

Kuwait 0.2**

Oman 0.6

South Africa(~2000) 0.3

Kazakhstan 0.4

Bhutan 0

Nigeria 0.03 * BCG Pasteur strain is also used and In 1976 in the Kingdom of Saudi Arabia (KSA) only 4.0% of the immunized individuals had BCG vaccination.

https://www.longdom.org/open-access/bacillus-calmettguerin-bcg-vaccination-an-overview-from-saudi-arabia-jaa-1000135.pdf

** Kuwait used the BCG Pasteur strain from 1962 to at least 1990. I couldn't find when Kuwait switched to the BCG Tokyo strain but the majority were vaccinated with the BCG Pasteur strain.

https://www.ingentaconnect.com/content/iuatld/ijtld/2002/00000006/00000006/art00002#

*** https://www.wjpls.org/admin/assets/article_issue/41072019/1564535230.pdf says that Iraq changed from the Denmark strain to the Japan strain but it doesn't tell when.



(Added on 5 Apr) Let's do simple math. The New York state has 19 million population and Japanese consists of 0.3%, 52 thousand. As there happened 3,565 deaths by COVID-19 so far, there should be 0.3% = 10 deaths of Japanese. I have never heard of death or even severe conditions of Japanese living in the New York state. If we assume the death by COVID-19 comes equally to any people no matter of BCG vaccination, the possibility of no Japanese death in NY state so far is 0.01%. Even if we assume the number of Japanese to half (26 thousand), the possibility is 0.76%. Death by COVID-19 doesn't come equally at more than 99%. Also, this calculation dismisses another hypothesis that the virus has evolved into a stronger mutation when arriving in western Europe and the U.S.

(Added on 1 Apr) I am afraid that I hardly understand the mechanism of BCG vaccines but there seems to be a piece of medical evidence that BCG Tokyo works quite well against COVID-19. https://www.jsatonotes.com/2020/03/if-i-were-north-americaneuropeanaustral.html?showComment=1585702586835#c4287423548330968127

The website, http://www.bcgatlas.org/ , seems to have a lot of information about BCG vaccination though this is not perfect, either.

I am afraid that I cannot digest this detailed medical information. Expert explanations will be welcomed.

(Added on 31 Mar) Dr. Toshio Hirano, one of the best authorities in immunology, best known for his discovery of interleukin-6, the 17th President of Osaka University, stated that this hypothesis could be right from the perspective of our immune system, citing my blog article. https://en.wikipedia.org/wiki/Toshio_Hirano https://www.facebook.com/toshio.hirano.79/posts/2817509081662367

(Added on 19 Apr) Dr. Toshio Hirano and his colleague have published an article stating that the IL-6-STAT3 axis would be the key target to stop becoming severe from COVID-19. https://marlin-prod.literatumonline.com/pb-assets/products/coronavirus/immuni4349_S5.pdf

The below paper could be key to understand why and how the different BCG strains work against COVID-19 differently. Unique Gene Expression Profiles in Infants Vaccinated with Different Strains of Mycobacterium bovis Bacille Calmette-Guérin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1932948/

https://twitter.com/ipatrioticmom2/status/1250581527701762048 The below chart of the paper looks the key. BBCG=BCG Moreau(Brazil), DBCG=BCG Denmark, JBCG=BCG Japan(Tokyo). I don't really understand but BCG Tokyo has more effect on IL-6 fold increase than BCG Denmark or BCG Brazil. I hope immunologists explain this part.









I live in Tokyo and Brisbane and have been wondering why the spread speed is faster in Australia than Japan.

Tokyo is a very crowded city and it's impossible to keep the social distance. People are packed in a very crowded train twice a day and I expected a high speed of spread but the actual speed is low so far (though it's beginning to explode).

Here in Brisbane or the other Australian capital cities, the normal social distance is much longer than Tokyo and I expected a slower spread. But the speed of spread is faster.

I was wondering about this, and so far this hypothesis may seem to be the most plausible. Maybe ~60% probability.