There’s no vaccine for COVID-19, but data analysis by researchers at a major U.S. medical school suggest another vaccine, for something else, might be looked at for why the disease hasn’t been as disastrous so far for some people in some countries.
BCG is a vaccine against tuberculosis that’s been in use for almost a hundred years. Many people in Asia, South America, Africa, and Russia get it as infants. (If you have friends who were born outside the U.S. and wonder why they have a vaccination scar on their upper arm, that’s why.) Americans don’t. Most Europeans don’t. Why? Because (oversimplifying here):
- It isn’t super-effective preventing tuberculosis.
- Tuberculosis isn’t that big a threat in the U.S. or other major industrialized nations.
Says the U.S. CDC:
“BCG, or bacille Calmette-Guerin, is a vaccine for tuberculosis (TB) disease. Many foreign-born persons have been BCG-vaccinated. BCG is used in many countries with a high prevalence of TB to prevent childhood tuberculous meningitis and miliary disease. However, BCG is not generally recommended for use in the United States because of the low risk of infection with Mycobacterium tuberculosis, the variable effectiveness of the vaccine against adult pulmonary TB, and the vaccine’s potential interference with tuberculin skin test reactivity.”
We are not doctors. Normally we wouldn’t touch this kind of story. But the possible mitigating effects on COVID-19 of that vaccine designed to prevent tuberculosis is something that’s kept coming up in our various social media feeds for several weeks now.
That’s mainly because we used to live in Japan, and our friends there are trying to figure out why COVID-19 hasn’t struck hard there, at least not yet. A lot of theories are batted around, including one shared by President Trump: that Japanese people don’t typically shake hands, which is true. Or don’t hug in public, which is also true, although getting squeezed into rush hour trains seems like more than a hug. Or that the school year in Japan starts in spring (although it may now be delayed), so many students there were already on break. Or that many Japanese citizens already wear face masks on public transportation, which again is also true, although there’s been a big shortage of masks in Japan for months. Or that the Japanese language doesn’t include many aspirated sounds, so it’s less likely people are accidentally spitting on each other in the course of normal conversation.
In other words, there are a lot of theories going around Japan about a lot of stuff, just like everywhere else. And people are hoping and praying things like that are true, because they don’t want to get sick.
Really, only time and testing will tell. As one doctor we contacted today replied: “tricky business making correlations early in the game.”
So when our friends in Japan–and also the biggest TV network there (for which we used to work)–started posting a bunch of stories about the BCG vaccination, we were intrigued, and dutifully translated many of them into English (via Google translate). Many of those original stories were highly speculative and non-scientific, written by laypeople noodling around with different theories (or perhaps even wishes) that the virus would not strike them as severely as it has elsewhere. And their posts were met with skepticism among other Japanese friends, who felt they might just be looking for hope in the face of what may be dark days ahead, and even frankly with us.
For the simple reason that even we know a virus follows the most opportunistic route to infection, which can be, but is not necessarily the most direct route geographically. Meaning the most likely explanation for why there hasn’t been an explosion of cases in Japan is–for whatever reason–the exponential growth of cases we’ve seen in so many other places just hasn’t happened there yet.
We felt there was a second huge problem with the BCG theory backers: nobody had any kind of explanation for China. Because everybody in China also gets a BCG vaccination. And that’s where COVID-19 first took hold and has had huge and deadly impact.
This morning, one of our old friends from when we lived in Japan alerted us to a pre-print of a paper emanating from one of the biggest medical schools in the U.S. It’s dated about a week ago.
As we go forward today, we need to keep in mind this is an analysis of data, not a clinical study. And the authors’ conclusion is not that they’ve already proven anything conclusive; rather they’re making a case that “randomized controlled trials using BCG” should be done.
The starkness of this chart, which is from that paper, should at least provide some food for thought. Even among our non-Japanese friends, many of whom have been wondering aloud why COVID-19 seems to be a “1st world disaster”, impacting larger, more developed countries much more dramatically, so far.
The most common and likely explanation is again, it just hasn’t gotten to less-developed nations yet. International travelers who might’ve carried COVID-19, typically go back and forth between the U.S. and the U.K. and China and Italy, etc., in far greater numbers than travel to small countries in sub-Saharan Africa.
This paper from the New York Institute of Technology’s College of Osteopathic Medicine however, suggests the possibility of something more:
“We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies.”
“Italy, where the COVID-19 mortality is very high, never implemented universal BCG vaccination. On the other hand, Japan had one of the early cases of COVID-19 but it has maintained a low mortality rate despite not implementing the most strict forms of social isolation. Japan have been implementing BCG vaccination since 1947.”
“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’”.
“Our data suggests that BCG vaccination seem to significantly reduce mortality associated with COVID-19.”
OK. But what about China? As we mentioned before, one of the big reasons we’ve been highly skeptical of all the talk about BCG in Japan is because China also gives everybody a BCG vaccination. And yet is Ground Zero for the disease. So does this paper explain China?
It does. But compellingly? You decide.
It argues that Mao’s Cultural Revolution in the 1960s and 70s, significantly weakened tuberculosis prevention, as many public health agencies were disbanded. (It bases this on a 2012 report from the Chinese Journal of Antituberculosis.)
So, another question to ask is does this theory of possible BCG efficacy seem to be playing out right now in places other than maybe, possibly Japan? Particularly in areas where the virus has made inroads, but perhaps not as much as the countries worst hit? And again, it’s hard to tell. South Korea and Singapore are widely credited with implementing colossal testing and tracking programs, which seem to have successfully limited the spread. Both those countries do BCG vaccinations. So how can you tell (without time) where one seeming success might end, and another begin?
A fair number of the people promoting the idea of further examining a role for BCG vaccines point to a couple of other sets of countries that are geographically very close: Spain and its neighbor Portugal, and Ireland and Great Britain.
Both Portugal and Ireland give BCG vaccines to infants. Spain and Great Britain don’t. And the number of deaths–so far–in Portugal and Ireland has been far less as a percentage of population than with their neighbors (in the case of Spain and Portugal, they’re actually sharing the same land mass.) That’s not to say cases aren’t going up in Portugal. They are. So again, it could still be about catching up and not somehow being better protected.
As we are writing this, there are 160 deaths reported in Portugal, and 8,269 in Spain. (Both according to www.worldometers.info.) Spain has almost 5 times the population of Portugal. Based on percentage of population, Spain has almost 10 times more deaths. But we’ll point out again, that could just be because Portugal is behind in the curve.
1,789 deaths in the U.K., 54 in Ireland. The U.K. has about 13 times the population of Ireland. And according to the BBC, the infection rates in Ireland have actually been going down, meaning more and more people are still getting COVID-19, but in fewer numbers than the day before. Which is the trajectory virtually everyone’s trying to get on right now.
Here’s something that can help you visualize a lot of what we’ve been talking about: the BCG World Atlas. Click on it, and then you can click on any country and check whether BCG vaccination is widespread in that country or not:
So, should clinical research, testing and maybe even treatment with BCG become a priority? There are a lot of priorities out there right now. And even if BCG looks like it could make a difference, is it a bigger potential difference than other interventions, therapies or treatments that are being looked at?
And there are a lot more questions that would need to be answered. For instance, would giving a BCG vaccination to someone who’s already sick lessen the chance of that person dying? In other words, even if it proves to be helping in some defensive way for people who had the vaccine years ago, is it also potentially curative?
Or is BCG best examined as a prophylactic? (That’s what the authors of the paper seem to conclude.) According to Science Magazine, some clinical trials are already started, especially aimed at finding protection against COVID-19 for older people and healthcare workers.
This is slightly beside the point, but BCG is already used effectively for purposes other than protection against tuberculosis. In fact, it’s been used for decades even in the U.S. to treat bladder cancer. But no one knows why it works for that. Here’s a bit from a paper from last year on that, which can be found in the online library of the U.S. National Institutes of Health (remember, the following paragraph refers to using it to treat bladder cancer, not COVID-19):
“BCG is the only intravesical agent shown to reduce the risk of progression of [non-muscle invasive bladder cancer] to muscle-invasive disease. Despite over 40 years of clinical use, the precise mechanism of action for what has often been considered the most successful cancer immunotherapy in humans remains largely unknown.”
Let us leave you today with one of the things we found most interesting in the NYIT College of Osteopathic Medicine paper: it indirectly suggests that the best spots to study whether BCG has a role in helping prevent or cure COVID-19, might be places like New York. That’s because those cities have huge immigrant populations, many of whom come from countries where they received the vaccination as children. Yet their exposure to the disease was presumably exactly the same as other people in the same city. So an assessment of whether people who had received the vaccination were infected at a lower rate than people who hadn’t, should be able to happen pretty fast. That is, when testing and monitoring becomes more available, organized, and widespread.