In the desperate search for ammunition to fend off the Covid-19 pandemic, a decades-old tuberculosis vaccine, given in huge numbers around the world, is gaining newfound attention.

Researchers in Australia and the Netherlands are testing the idea that the vaccine, known as BCG — short for bacille Calmette-Guérin — could have broad power to boost the immune system against the novel coronavirus. In the United States, a research group in Boston hopes to test the vaccine in frontline health workers for the same purpose.

The interest stems from multiple studies over a number of years that point to the vaccine as having what are known as “off-target” benefits.

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While the vaccine, used in many low- and middle-income countries, isn’t considered to be highly effective against its primary goal, TB, it seems to help the immune system fend off various pathogens, including one that causes leprosy. The question is whether the virus known as SARS-CoV-2 is among them.

Not everyone is convinced.

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A leading TB researcher, Madhukar Pai, has warned that the BCG vaccine is unlikely to be the magic bullet some people seem to think it may be. Pai, director of McGill University’s International TB Center, wrote a blog post over the weekend arguing that people may be ascribing almost magical powers to the vaccine.

“I think the idea is 100% worth investigating,” Pai said in an interview with STAT. “That’s why my piece was not against further research. My piece was saying: Right now we’re nowhere close to anything for a policy based on ecological studies that are full of holes.”

The World Health Organization seems to agree. On Sunday it published a scientific brief examining the evidence surrounding BCG. It concludes that there currently is no proof the vaccine protects against the new coronavirus. “In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19,” it stated.

Still, some researchers are hopeful.

Denise Faustman, director of immunobiology at Massachusetts General Hospital, has been studying BCG for years as a therapy for type 1 diabetes. She has a stash of the vaccine — which is not used in the United States for tuberculosis prevention — and wants to see if it could benefit frontline health workers. She is seeking institutional permission to quickly mount a trial at Boston’s Brigham and Women’s Hospital.

“The goal is to enroll rapidly over a two-month period, about 4,000 high-risk health care workers. And then the goal will be to watch them … to see if we can get a signal,” Faustman said.

The word has gotten around among health workers in Boston. Faustman’s phone is ringing off the hook. “Certainly the people who want in the trial are calling every five minutes [to ask], ‘How do I get in this trial?’” she said. “We have hundreds of phone calls right now of ‘Why can’t I get this?’”

In some respects, the notion of using a vaccine designed to prevent infection with one pathogen to protect people from another, unrelated bug seems counterintuitive. You wouldn’t expect a flu shot to offer any protection against Covid-19, for instance.

But years of research has suggested the immune system boost that BCG confers applies far more broadly than to just Mycobacterium tuberculosis, which causes TB. Children vaccinated with it in low- and middle-income countries around the world have been seen to have lower death rates from other respiratory infections, for instance.

Faustman is enthusiastic about the vaccine, hoping it will be shown to offer protection and could be used as a tool to safeguard critical health workers until a vaccine specifically developed to ward off Covid-19 infection is available. “That’s our goal.”

Pai agrees the study is worth doing. “Is there a signal to do additional research? I think the answer is yes. We’ve known that BCG has these non-specific effects against multiple [diseases],” he said.

But he also argues that proponents of using the vaccine to protect against Covid-19 are wrongly trying to ascribe differing death rates around the globe to a country’s use or non-use of BCG.

Pai and his group at McGill compiled the data everyone is making these inferences from, an online resource called the BCG World Atlas. It lists whether a country uses BCG, when the program was introduced or discontinued, and when it is given, among other things.

A number of studies, most of which have not yet gone through peer review, have suggested lower Covid-19 case numbers or death rates in some countries can be attributed to their use of BCG — drawing from the BCG Atlas.

“Suddenly everybody and their brother has found the atlas and then taken their Covid data from the WHO or from Johns Hopkins University or wherever, overlaid the two and run regression models and [said] ‘Oh, look here. BCG works,’” Pai said.

That kind of approach is flawed, he said, and doesn’t factor in that different outbreaks around the world are at different stages. That’s important because countries that have seen transmission more recently haven’t experienced the explosion of deaths seen in countries like Italy, Spain and the United States. Likewise, many low- and middle-income countries are not testing for Covid-19 in large numbers; their low case and death rates are more likely the result of under-reporting than of the BCG vaccine, Pai said.

The WHO’s statement also challenged the studies attempting to draw conclusions based on countries where BCG had been used. And it, too, pointed out that a run on the vaccine could create real damage. “BCG vaccination prevents severe forms of tuberculosis in children and diversion of local supplies may result in neonates not being vaccinated, resulting in an increase of disease and deaths from tuberculosis,” the global health agency said.

Pai worries that low- and middle-income countries that use BCG may buy into the untested hype around the vaccine and assume their populations have protection that they may not have. Only clinical trials can answer this question, he said.

“It would be dangerous for policymakers to assume protection from BCG and not act,” Pai said in his blog post in Forbes. “Researchers and journalists need to be responsible as well, and not raise false hopes based on weak evidence. And countries should not hoard BCG vaccines for Covid-19, since the BCG supply chain is weak, and really necessary to protect children in [low- and middle-income countries] from childhood TB.”

  • In 1976, prior to myself and my family going to malaysia on attachment (RAAF) we were all given BCG injections. Could records be scrutinised to see if any covid-19 has infected these people. maybe nothing but its worth having a look at.

  • Wow, Scott, if you had metastatic malignant melanoma and are still with us 39 yrs later, it must really have been effective for that purpose. And yet, I haven’t heard about its use in this way for years. Twice monthly? By intradermal injection? Or how? Where? I remember them using it at Duke when I was in MS.

    • I was vaccinated at birth back in 1978 at the Rankin memorial hospital Greenock Scotland. I was born with polio & jaundice so received a full spectrum of vaccines. In my 40+years of live I have suffered with all that live can throw me including chickenpox 4 times, shingles, flu & the common cold quite a few time.
      With each illness I have had I have been lucky enough to bounce back in a very short space of time with the flu I contracted my recovery time was only one week (it was a very aggressive flu may I add).
      Something I have noticed is my body goes into a kind of limp mode or shut down during this period I sleep alot & sweat profoundly also I consume a lot of fluids but eat very little this normally lasts 4-7days however I recover quite well.
      My belief is this is due to the fact my immune system was given that boost at birth & also looking at my family history. I also am convinced that due to the fact that in Scotland we still use the BCG vaccine in schools could in part contribute to the low death rate from COVID-19/ SARS COVID 2.
      Only time & research will tell. It would be interesting to see a breakdown of COVID-19 deaths in Scotland by age/immunization/ health problems, this is unlikely because under Scottish health policy (hence why we have the highest drug related death rates, we cover the full spectrum of deaths even those whom have died while under medication as drug related).
      I have always believed in vaccination & those who decide to anti vaccine at putting other lifes at risk (just look at how measles was almost completely eradicated in the US & since more anti vaccination groups have came up the disease has made a comeback.

  • What about the news of China using BCG vaccine for everyone just before outbreak? Is in it suspicious?

  • Dr Pai is not only right but he is forthcoming in Warning to the countries not to get lured by BCG vaccine protection against the Corona Virus.I endorse his views fully
    I just want to add few points to make Dr Pai’s advice more forceful :
    1. BCG produces cell mediated immunity which takes minimum three months or more to confer protection against TB .
    2. Protection provided by it is measured by doing tuberculin testing which requires differently skilled staff and can’t be trained overnight .
    3.Even if it is proved by doing serial / Longitudinal ecological studies that BCG provides innate immunity to many other organisms.It should be considered as a good observational study and a blessing to all the countries which are providing BCG at birth underUIP . They should carry should carry the vaccination with more seriousness.
    4. Secular epidemic curve of any virus is usually of weeks/ months so no clinical trial of BCG can give any result as by the time the pandemic is over .
    The Chingleput clinical trial of BCG done in India took 11 years to give the first follow up results It was followed for 23 years . I am not touching the financial operations, technical and other aspects just highlighting the enormity.
    While secular curve of Tuberculosis runs for centuries and now it is on descending limb of the curve that it keeps on killing thousands of people without getting any attention as it kills a person silently after a long suffering even if it kill few everyday .
    So let us not distract from whatsoever we are doing against Covid -19 as individual countries by focusing on BCG . We leave it to do it’s role silently for which is meant .

  • One small additional problem w BCG is that it converts the PPD skin test to a false positive which diminishes the value of the skin test in otherwise PPD negative individuals. Trivial?

  • Totally not an expert in anything relevant, but… if BCG boosts the immune system *in general*, at least against respiratory infections, why doesn’t everyone get it? (I know the article says the supply chain is weak, but that wouldn’t remain true if e.g. the US recommended everyone should get it.)

    Are there bad side effects?

    • Policy on BCG vaccination was revised by WHO after BCG trial in India in1980 or so to give BCG at birth so as to protect children from childhood form of tuberculosis .
      Most of the developing countries adopted it as in these countries the risk of infection is early due to high prevalence of Smear positive cases.
      Some countries adopted policy of giving BCG at school leaving age as they belong to low endemic countries. USA, Canada and many European Countries at that time decided to stop giving BCG .
      Now over a period of 40 years other benefits of BCG have started appearing so it is a policy decision and cannot be taken in a hurry at the time of crisis
      There are no serious side effects due to BCG
      The first question that it produces false PPD positive reaction. ? It can be differentiated .
      Again one needs expertise I can’t explain here
      Even doing epidemiological surveys one can differentiate by overlapping the two graphs now it is still easier due to recent advances.
      I mean if BCG is to be adopted as national vaccination policy these are very minor issues.

    • Most of the developing countries adopted BCG at birth as in these countries the risk of infection is early due to high prevalence of Smear positive cases.
      Some countries adopted policy of giving BCG at school leaving age as they belong to low endemic countries. USA, Canada and many European Countries at that time decided to stop giving BCG .
      Now over a period of 40 years other benefits of BCG have started appearing so it is a policy decision and cannot be taken in a hurry at the time of crisis
      There are no serious side effects due to BCG
      The first question that it produces false PPD positive reaction. ? It can be differentiated .
      Again one needs expertise I can’t explain here
      Even doing epidemiological surveys one can differentiate by overlapping the two graphs now it is still easier due to recent advances.
      I mean if BCG is to be adopted as national vaccination policy these are very minor issues.

    • Some countries adopted policy of giving BCG at school leaving age as they belong to low endemic countries. USA, Canada and many European Countries at that time decided to stop giving BCG .
      Now over a period of 40 years other benefits of BCG have started appearing so it is a policy decision and cannot be taken in a hurry at the time of crisis
      There are no serious side effects due to BCG
      The first question that it produces false PPD positive reaction. ? It can be differentiated .
      Again one needs expertise I can’t explain here
      Even doing epidemiological surveys one can differentiate by overlapping the two graphs now it is still easier due to recent advances.
      I mean if BCG is to be adopted as national vaccination policy these are very minor issues.

  • BCG has long been a standard treatment for early stage bladder cancer (I have been a patient). It has modest but significant positive impact on the immune system, but also significant side-effects after extended use.

  • I took BCG twice a month for 18 months…….39 years ago as a immuno-booster for metastatic malignant melanoma. I wonder if I might still have that working for me.

  • Although I am a (moderately) big fan of BCG’s immunomodulatory properties, the evidence that a number of countries, like France, UK, etc., where the vaccine was mandatory, and yet they suffer a high number of infections/deaths, is empirical evidence it is not moving the needle.

    • No, BCG has not been mandatory in the UK. I had it because a girl at my school had TB; everyone at the school had the BCG vaccine because of that but in general most people did not get it. It was only done as a result of contact tracing. I’ve still got the scar – a circle of little dots. If you check, most people in the UK won’t be able to show you the scar.

    • @ Judith B
      if that’s the case I beg your pardon. According to wiki it was enforced between 1953 to 2005. Feel free to replace UK with Sweden or other country. The substance still stands. Cheers

    • I’m 41 and been resident in the UK since age 5. My entire school year received BCG at age 12/13 (e.g. in 1990/1991).

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