Coronavirus and vaccination against tuberculosis: does it really provide immunity

In late March, when the COVID-19 epidemic spread around the world, and the number of confirmed cases began to be measured in the hundreds of thousands, many drew attention to a characteristic coincidence, reports Air force.

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In different states, the disease spreads at different rates. And for some reason, a coronavirus infection (at least at first glance) is significantly less active in countries where children are necessarily vaccinated against tuberculosis with the help of the BCG vaccine, including in Russia.

Is this just a coincidence? Or is there some kind of pattern here?

Given the scale of the epidemic and the fear of a new virus, which many are only fueling the unprecedented restrictive measures introduced around the world, a variety of versions instantly began appearing on social networks and various kinds of semi-scientific sites.

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Someone seriously believes that the vaccine against tuberculosis, invented 100 years ago, can at the same time protect against coronavirus infection, the existence of which scientists did not know until December last year.

Others, on the contrary, argue that there is no connection and cannot be: the coincidences are random, and the immunity from coronavirus that the vaccine supposedly provides and in which many so want to believe is a fiction, there is no scientific evidence of it.

So what does science say and what do we know for sure?

Characteristic coincidence

Until about mid-February, when a practically unstudied disease was raging only in China, it seemed that the new virus was mowing down everyone indiscriminately with a wide scythe - however, more often giving preference to men.

However, when the virus reached the most remote corners of the planet, it became obvious that the epidemic developed in different countries in different ways.

For example, in Italy or the United States, the number of confirmed cases of infection and deaths of patients soon begins to grow by the hour and not by the day. While in Japan or Thailand, the epidemic is spreading much more slowly, despite the fact that the first patients were detected there much earlier.

Many factors influence this: a huge role is played by the average age of the population, as well as cultural norms, the state of the healthcare system, the experience of previous epidemics, and so on. In addition, the description of the course of epidemics in specific countries depends on how the testing is organized, how statistics are kept and information is provided.

However, some scientists and analysts have suggested that there is another factor - the speed of development and severity of the epidemic in a particular country correlates with whether BCG is mandatory for children there.

This theory is based on public statistics on coronavirus infection. Physicians involved in research say that the presence of BCG in a particular person certainly does not give him immunity from the new virus. Vaccinated patients are among severely ill patients, and among those killed by COVID-19.

At the same time, it cannot be ruled out that during a pandemic, vaccination may be useful on a national scale: in any case, preliminary data from this theory do not contradict.

The first specialized study on this topic was published at the end of March by a group of scientists from New York. It has not yet been officially peer-reviewed by other scientists working in this field, however, the authors of the work make a very bold statement.

“Our data suggest that BCG vaccination appears to significantly reduce mortality from COVID-19,” they wrote. “We also found that the earlier a country started BCG vaccination, the greater the reduction in deaths per million inhabitants.”

Epidemiologists from the University of Texas conducted an even larger study, examining statistics from 178 countries, and came to the same conclusion. According to their calculations, the number of people infected per capita in countries with mandatory vaccination against tuberculosis is approximately ten times lower, and the number of victims of COVID-19 is 20 times lower than in countries where BCG is no longer given.

What kind of vaccine is it that is so special?

“Vaccination against everything”: first attempt

Developed in France back in 1921, BCG (from the French Bacillus Calmette-Guérin - Calmette-Guérin's bacillus) remains today the only accessible and effective vaccination against tuberculosis recommended by WHO.

It works just like any other vaccine. A weakened infectious agent is injected into a healthy person in order to “introduce” the body to the potential danger and develop specific immunity.

Specific means directed against a specific virus or bacteria that causes a particular disease. That is why there are so many vaccinations: for each disease there is one.

The BCG vaccine is designed specifically to protect against tuberculosis, and in theory, it cannot and should not be protected from anything else.

However, scientists Peter Aabi and Christina Stabell-Benn (both Danes, but work mainly in Guinea-Bissau) have been studying the side effects of vaccination for many years and claim that BCG provides effective protection against other diseases, strengthening immunity in general.

If you believe their research, which has been going on for several decades, people vaccinated with BCG become on average 30% less susceptible to all infections known to science, without exception. Whether it is a pathogenic virus, bacteria or fungus, it makes no difference: the likelihood of infection is reduced by almost a third.

However, all these years, the scientific community has been pretty cool about the work of Aaby and Benn. Their publications in scientific journals have repeatedly been criticized for inaccuracies in the methodology, and a large-scale WHO study in 2014 finally decided: if BCG has any additional advantages, then they are so small that they should not be taken into account.

At this point the story could be considered closed. But in 2020, the coronavirus pandemic struck, and scientists noticed unexpected numbers and strange correlations.

Italy, USA ... who is next?

There are not many countries in the world where vaccination against tuberculosis has never been compulsory and universal. They can literally be counted on the fingers: Belgium, Italy, Canada, Lebanon, the Netherlands, and the USA.

BCG is given there selectively - to certain categories of the population and only as a recommendation.

Two countries on this list have long been among the sad leaders in the number of confirmed cases of COVID-19. More than a quarter of all “officially infected” people in the world live in the United States. In Italy, whose population is five times smaller, it is every tenth.

Three more countries are not in the top ten in absolute numbers, but follow each other immediately after it: Belgium in 11th place, the Netherlands in 12th, Canada in 13th.

Moreover, all three are far ahead of, say, Japan or Thailand, where the population is several times larger, and the first cases of coronavirus were recorded much earlier. If in Japan, a population of 126 million, less than 19 people have died from COVID-100 during the entire epidemic, then in Belgium, a population of 11 million, there are already over 2000.

The Institute of Economic Analysis, founded by economist Andrei Illarionov, studied the statistics of deaths and infections from 36 countries where the “explosive” stage of the coronavirus epidemic began more than a month ago, and compared them with the vaccination policy pursued there.

Calculations provided by the institute showed: in six “unvaccinated” states, the COVID-19 epidemic is growing much faster than in countries where BCG is still mandatory. Both in terms of the total number of infected per 1 million population, and in terms of the number of deaths.

Countries where they used to vaccinate everyone without exception, but at some point stopped, are not inferior to the “unvaccinated” ones in the number of detected cases, but the proportion of deaths there is several times lower.

A similar analysis was carried out by experts from the Institute of Developmental Biology (IDB) of the Russian Academy of Sciences. There, countries were divided not into three, but into two categories: those where compulsory BCG vaccination has not been carried out for at least 30 years (Belgium, Germany, Spain, the Netherlands, Switzerland), and those where it is still included in the national vaccination calendar - both in the EU (Bulgaria, Hungary, Latvia, Poland, Romania, Slovakia) and in other regions (Hong Kong, Indonesia, Kazakhstan, China, Mexico, Philippines, South Korea, Japan).

Unlike Illarionov, biologists intentionally did not include Russia in the US list, where the epidemic began later, but otherwise the results of both studies were very close.

“In the second group, the prevalence of COVID-19 was significantly lower, which confirms the hypothesis about the possible protection of the BCG vaccine against COVID-19,” says a letter that Russian scientists sent to the Lancet journal.

At the same time, IDB experts emphasize: “Differences between these groups of countries could potentially be due to other factors and only indirectly be related to BCG vaccination.”

Numbers trap

Is it possible that such an obvious connection, confirmed by several studies at once, is due to some other reasons?

Of course, and statistics know a lot of similar examples. For example, the number of fire engines sent to the place of ignition is directly related to the damage from fire, since both indicators depend primarily on the size of the fire. However, this does not mean at all that the damage can be reduced by sending fewer fire crews into place.

Irina Lyadova, a professor at the IDB RAS, provides two possible alternative explanations for the close relationship between BCG and the spread of coronavirus.

Firstly, compulsory BCG vaccination is carried out by countries with a relatively high incidence of tuberculosis. Many of them (although by no means all) are very poor states, and this can reduce the level and quality of testing and create the appearance of a more prosperous situation with COVID-19.

Secondly, the severity of the epidemic in different countries is strongly affected by the speed of adoption and the level of quarantine measures introduced.

“We cannot completely exclude the existence of a connection between this indicator and the BCG vaccination policy, since both indicators depend on the historical characteristics of the organization of epidemiological services and health care systems,” she notes.

“Thus, it is not yet possible to completely exclude the fact that in countries using the BCG vaccine, a more favorable course of the epidemiological process is not directly related to the protective activity of BCG, but to other factors,” concludes Professor Lyadova.

"Trained immunity"

Do biologists have any fundamental reason to believe that a TB vaccine can help with other viral infections?

There are such reasons, and for the first time this mechanism was described in an article published in the journal Science in 2016. Its authors from the Netherlands suggested that the memory of our immune system can be formed not only due to mutation or recombination of some genes (this is how vaccinations work ), but also without physical changes in DNA.

The work of a group of scientists from the Netherlands was called “Trained Immunity”, and there was not a word about BCG. However, the researchers decided to test their theory with the help of this vaccination (and double-blind testing).

As a result, they were able to prove in practice that BCG can protect the body from infections that have nothing to do with tuberculosis. It worked first with yellow fever, and then with other viruses. Vaccinated people became infected less often than the control group. But even if they caught an infection, they were not so sick and recovered faster.

But what about coronavirus? Does this mean that BCG can have a similar effect here?

All experts emphasize: to argue that the vaccine really makes people less susceptible to the SARS-CoV-2 virus, it will be possible only by the results of appropriate clinical trials.

This is the only scientific way to check whether a correlation has a causal relationship.

“Yes, this is only a correlation, but the hypothesis has a scientific basis - in the form of both recent and rather old studies published in serious journals,” says Dmitry Kuprash, professor of the Department of Immunology at Moscow State University and corresponding member of the Russian Academy of Sciences. “Doctors are doing the right thing by testing this hypothesis.”

Tests have already begun and are being carried out in several countries at once. In Australia, where BCG has not been done for almost 40 years, 4000 young hospital staff are scheduled to have BCG.

Although Ancha Baranova, a professor at the School of Systems Biology at George Manson University of America, doubts that the protective effect of BCG from the severe course of the disease can be convincingly proved in adults. There is considerable evidence that childhood vaccination is more effective.

Pending Results

In the Russian Research Institute of Vaccines and Serums, they confirm: evidence of a connection between BCG vaccination and a reduced risk of various non-mycobacterial infections, allergies, cancer and general mortality does exist.

“Such nonspecific effects of BCG vaccination may be mediated by cells of the innate immune system, and not by specific memory T cells,” explains Oksana Svitich, director of the institute, corresponding member of the Russian Academy of Sciences.

Without going into details, after vaccination, innate immune cells remain in an activated state for quite a long time: they secrete substances that prevent inflammation and acquire the ability to “shift” the immune response, providing protection against any bacterial and viral infections.

In addition, the vaccine can stimulate the so-called heterologous immunity, simultaneously activating specific T-lymphocytes of other antigens.

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“Thus, BCG vaccination cannot provide specific protective immunity against coronavirus, but a nonspecific protective effect is possible due to activation of the innate immune system,” says Svitich.

At the same time, she believes that even in this case, “this is unlikely to affect the speed of spread of the epidemic in countries with different approaches to vaccination against tuberculosis.”

Whether it is true or not, it can only be said from retrospective studies when the pandemic is behind. Even the results of ongoing clinical trials will not appear until the end of December.

As reported by ForumDaily:

• A new virus was discovered in the Chinese city of Wuhan in December 2019. In 2020, it covered all continents except Antarctica. On March 11, US President Donald Trump imposed a ban on entering the United States from EU countries. The ban came into force on Friday, March 13, and will last at least 30 days. In particular, it will concern people who have visited the Schengen area over the past 14 days.
• March 13 Trump due to coronavirus introduced a nationwide emergency regime in the US.
• On March 11, WHO recognized the situation with the coronavirus pandemic, which covered more than 110 countries. Symptoms of Coronavirus COVID-19 Disease Available here.
• Virologist's tips on how to protect yourself from infection - here to register:.
• Taking advantage of the panic in the society because of the epidemic, fraudsters came up with several schemes to deceive victims of personal data and money. The most common ones can be found here.
• Having succumbed to panic due to a state of emergency, Americans are massively buying toilet paperbut they cannot explain why they need it during the epidemic.
• Trump has signed into law on paid leave due to coronavirus. Who can count on paid leave, read here.
• Read all news about coronavirus in our special project.

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