The novel coronavirus is rampaging across the world, but its impact is not equal: it is hammering some populations, while leaving others relatively unscathed.

Why is that so? There are multiple possible metrics which include government policies, national health services’ quality and resources, population densities, social behavior, treatment preferences, etc.

In the latter metric, it is emerging that one determining factor in morbidity and infection may be a 100-year-old tuberculosis vaccine.

The three hardest-hit counties – the US, Italy and Spain – do not use it. However, countries that have been lightly hit – including Australia, Japan, New Zealand and South Korea – do.

Countries that use it in their vaccination programs had a fatality rate of four per million people, according to a recently published study. Conversely, people in countries who do not vaccinate with it were 10 times more likely to die at a rate of 40 deaths per million people.

Stark differences in mortality ratios between countries with and without BCG vaccination programs. Image: Jake Adelstein, from data in article

It is not only mortality. Infection rates also appear to be strongly impacted positively by the vaccine, BCG (Bacillus Calmette-Guerin).

BCG is no modern miracle. It was developed by French physicians and biologists Léon Charles Albert Calmette and Jean-Marie Camille Guérin in the 1900s and first successfully tested in 1921.

While there is no surefire cure for Covid-19, both medical weapons and medical armor are being deployed in the war against the coronavirus. In this sense, BCG could provide a potent flak-jacket.

Researchers in Australia, the Netherlands, the US and other countries are taking a close look at BCG. Now researchers in at least four countries are running clinical trials that give healthcare workers and sometimes elderly people the BCG vaccine to ascertain whether it can provide protection.

The impetus began, more or less, with a single study.

Japan inspires first study

Gonzalo Otazu, an assistant professor of biomedical sciences at the New York Institute of Technology, who studied for his PhD in Japan, became curious about the small number of coronavirus deaths in the country.

“We were discussing with Japanese friends why Japan was not hit as hard [by the virus as other countries],” he told Asia Times in an email last week. “That is the origin of the preliminary study.”

The resultant study was posted on March 25 on medRxiv, a site that releases finished, but not yet peer-reviewed, studies. It is entitled Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study.

Epidemiology is the branch of medicine that deals with the outbreak, distribution and possible control of diseases and other factors relating to health.

Otazu and his team found a striking correlation between countries that required citizens to be vaccinated with BCG and countries with a fewer number of confirmed Covid-19 cases and deaths.

His study suggests that the different impacts of Covid-19 in different countries could be partially explained by the different national requirements regarding BCG vaccinations for children. He also suggests that BCG vaccinations might be a factor in the infection rates and Covid-19 mortality rates per country.

“We found that countries without universal policies of BCG vaccination, such as Italy, the Netherlands and the United States, have been more severely affected, compared to countries with universal and long-standing BCG policies,” he said. “Japan has not implemented strict social isolation policies and it has been relatively spared compared to Italy.”

Italy, which has never had a BCG vaccination program, has a fatality rate of 292 people per million. Nearby Germany’s fatality rate is less than one-tenth of Italy’s, at 28 people per million. The vaccine was widely implemented in East Germany, and there are reportedly fewer deaths in that region versus the rest of the country.

Other countries with a national BCG requirement, like Japan, South Korea and New Zealand, have suffered fatality rates at the low end of the global scale.

Complicating the picture is timing. Otazu says that the year BCG policies were implemented or halted has a significant influence on the damage caused by the novel coronavirus and its spread.

His research team argued that people in countries where the BCG vaccination policy was established earlier have a larger number of elderly protected, and seem less likely to face life-threatening illness.

People in countries that had a late start to their BCG programs, like Iran, have a higher risk of death, possibly because their elderly – a very high-risk population – did not have the vaccination.

Some of the team’s key findings regarding national policies were as follows:

Iran implemented the BCG requirement in 1984. Late start.

Japan started its BCG vaccinations as early as 1947. There is a low risk of death even though there is no strict social isolation. Japan has about 100 times less deaths per million people than Iran; Japan averaged 0.28 deaths per million.

Spain, France and Switzerland discontinued universal BCG policies.

The US, Italy and the Netherlands have not adopted universal BCG requirements.

Otazu is not the only researcher to zero in on BCG.

A study of 178 countries led by Paul Hegarty, a urologist at Mater Hospital in Dublin, which was uploaded on a medical research website on March 27, was entitled “BCG vaccination may be protective against Covid-19.”

Like Otazu’s study, it showed that countries with BCG vaccination programs had remarkably lower fatality rates than countries lacking them. Infection rates also seemed to be slowed by BCG.

The incidence of Covid-19 was 38.4 per million in countries with BCG vaccination, Hegarty’s team found, but was 358.4 per million in countries without such a policy.

Moreover, the death rate was 4.28 per million in countries with BCG programs compared with 40 per million in countries without such a program.

South Korea, Japan, Singapore, Thailand and Hong Kong generally administer the vaccine after birth. These countries had 0.7 deaths per million (as of April 10), while Taiwan had only 0.2 deaths per million. Taiwan has had a BCG program since the 1950s, but was vaccinating in the 1940s as well, according to the CDC of Taiwan.

Taiwan, which unlike Japan has employed extensive testing, only had 16 cases of coronavirus per million, probably due to efficient quarantines based on that testing. Japan has roughly 37 cases per million, despite suppressing testing prior to the postponement of the Tokyo 2020 Olympics.

The study concludes: “BCG has been used for close to a century and three billion doses have since been administered since it was developed in 1922 with a remarkable long-standing safety record. For individuals previously vaccinated, recent studies have demonstrated revaccination is safe, well-tolerated … While awaiting a coronavirus-specific vaccine, using an existing, available and safe vaccine such as BCG to boost host immunity may represent an important tool against coronavirus.”

Training immune systems

BCG is a curious thing that is not unknown in the medical world – a kind of magic charm that appears to do more than its intended purpose. While it was invented to prevent tuberculosis, it has proven to do much more than that.

It has been shown to prevent meningitis, boost the immune system and improve resistance to other specific diseases and viruses. Elderly people vaccinated with it have fewer respiratory infections. In bladder cancer patients, BCG boosts immunity, reduces tumor size and decreases mortality.

Mihai Netea, an infectious disease specialist at Radboud University Medical Center in the Netherlands, has found that the vaccine appears to run counter to the textbook version of how immunity works. Netea asserts in a report in Science magazine that the vaccine stimulates a kind of cellular memory that helps the body fight off new pathogens, what is called “trained immunity.”

In other words, people vaccinated with BCG are better able to combat new illnesses because their immune system has been sensitized to deal with other disease microbes.

Interest grows

The original study by Otazu’s group has drawn great interest. Recent data seems to supplement its findings.

This week scientists in Melbourne, Australia, started giving the BCG vaccine or a placebo to thousands of healthcare workers, to see whether it can prevent infection or serious outcomes. A clinical trial of 1,000 healthcare workers has already started in the Netherlands.

In Japan, however, things are different. On April 9, the Yomiuri Shimbun, the conservative newspaper closely linked to Japan’s ruling political party, published an article critical of the interest in the BCG vaccine.

It noted the view that the vaccine might help prevent illnesses caused by the novel coronavirus is gaining credence world-wide. However, it summarized several vaccine experts as saying: “The truth of this is not scientifically proven. We don’t recommend [using it].”

This is an irony. The academic elite in Japan seem to show little interest in researching a possible treatment for Covid-19 that was first considered because of Japan.

However, many people in the country are aware of the possible benefits of the vaccine and are asking to be vaccinated or re-vaccinated.

As a result, the one and only maker of the vaccine in Japan, Japan BCG Laboratory, has shipped out three times the normal amount of product since the end of March.

The company has reportedly begun to try to lower the amount handled by medical supply wholesalers to regular levels. There is a concern there might not be enough for the infants who need it.

While correlation does not equal causation, there are valid reasons why the vaccine is generating so much interest – except in Japan’s stodgy medical community.

“It’s the talk of everyone in the medical community here,” a doctor who runs a small clinic in Tokyo, who asked for her name not to be used, told Asia Times. “Honestly, if a patient with a pulmonary disorder, or the other pre-existing conditions that make coronavirus lethal, asked me to vaccinate them with BCG, I would probably do it. I doubt it would be harmful and it might save their life. That’s my personal opinion.”

Japan began vaccinating children more than half a century ago, but while it has done a remarkable job of combating tuberculosis over the years, it has seemingly failed to stop the spread of Covid-19 in the country.

Tokyo’s lack of testing has drawn derision from both within the country and abroad.

When asked about a statement from the US Embassy that bluntly criticized Japan’s handling of Covid-19, Cabinet Spokesman Yoshihide Suga retorted: “Well, they said we have very few tests, but we also have few deaths.”

He may be right.

Statement

Otazu politely asked Asia Times to insert his full statement on why he thinks the BCG vaccine is effective against the coronavirus. This is it:

“Several vaccines including the BCG vaccination have been shown to produce positive ‘heterologous’ or non-specific immune effects leading to improved response against other non-mycobacterial pathogens. This phenomenon was named ‘trained immunity’ and is proposed to be caused by metabolic and epigenetic changes leading to promotion of genetic regions encoding for pro-inflammatory cytokines. BCG vaccination significantly increases the secretion of pro-inflammatory cytokines, specifically IL-1B, which has been shown to play a vital role in antiviral immunity. Additionally, a study in Guinea-Bissau found that children vaccinated with BCG were observed to have a 50% reduction in overall mortality, which was attributed to the vaccine’s effect on reducing respiratory infections and sepsis.”

Science writer and editor, Julianne Chiaet, contributed to this article.