Coronavirus & TB-vaccination

At the beginning of the week, I heard in the news that researchers in some countries will soon start a clinical trial of an unorthodox approach to the new coronavirus. They will test whether a century-old vaccine against tuberculosis (TB), a bacterial disease, can rev up the human immune system in a broad way, allowing it to better fight the virus that causes coronavirus disease 2019. I searched on that topic on the internet. That makes me happy and a little comfortable, since I was wondering why some countries are hardly attacked by the virus while others are not.



Although the study is randomized, participants will likely know if they got the vaccine instead of a placebo. BCG often causes a pustule (I already have one ;)) at the injection site that may persist for months, usually resulting in a scar. But the researchers will be blinded to which arm of the study—vaccine or placebo—a person is in.


“Note: this map existed more than 9 years ago”

A: The country currently has a universal BCG vaccination program.

 B: The country used to recommend BCG vaccination for everyone, but currently does not.

C: The country never had universal BCG vaccination programs.

For more details on BCG policies and its distributions in the globe, please check this “https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062527/


Scientific background:

BCG contains a live, weakened strain of Mycobacterium bovis, a cousin of M. tuberculosis, the microbe that causes TB. (The vaccine is named after French microbiologists Albert Calmette and Camille Guérin, who developed it in the early 20th century.) The vaccine is given to children in their first year of life in most countries of the world, and is safe and cheap—but far from perfect: It prevents about 60% of TB cases in children on average, with large differences between countries.

Vaccines generally raise immune responses specific to a targeted pathogen, such as antibodies that bind and neutralize one type of virus but not others. But BCG may also increase the ability of the immune system to fight off pathogens other than the TB bacterium, according to clinical and observational studies published over several decades by Danish researchers Peter Aaby and Christine Stabell Benn, who live and work in Guinea-Bissau. They concluded[1] the vaccine prevents about 30% of infections with any known pathogen, including viruses, in the first year after it’s given. The studies published in this field have been criticized for their methodology, however; a 2014 review [2] ordered by the World Health Organization concluded that BCG appeared to lower overall mortality in children, but rated confidence in the findings as “very low.” A 2016 review [3] was a bit more positive about BCG’s potential benefits but said randomized trials were needed.

Since then, the clinical evidence has strengthened and several groups have made important steps investigating how BCG may generally boost the immune system. Mihai Netea, an infectious disease specialist at Radboud University Medical Center, discovered that the vaccine may defy textbook knowledge of how immunity works.

When a pathogen enters the body, white blood cells of the “innate” arm of the immune system attack it first; they may handle up to 99% of infections. If these cells fail, they call in the “adaptive” immune system, and T cells and antibody-producing B cells start to divide to join the fight. Key to this is that certain T cells or antibodies are specific to the pathogen; their presence is amplified the most. Once the pathogen is eliminated, a small portion of these pathogen-specific cells transform into memory cells that speed up T cell and B cell production the next time the same pathogen attacks. Vaccines are based on this mechanism of immunity.

The innate immune system, composed of white blood cells such as macrophages, natural killer cells, and neutrophils, was supposed to have no such memory. But Netea’s team discovered that BCG, which can remain alive in the human skin for up to several months, triggers not only Mycobacterium-specific memory B and T cells, but also stimulates the innate blood cells for a prolonged period. “Trained immunity,” Netea and colleagues call it. In a randomized placebo-controlled study published in 2018, the team showed that BCG vaccination protects against experimental infection with a weakened form of the yellow fever virus, which is used as a vaccine.

Together with Evangelos Giamarellos from the University of Athens, Netea has set up a study in Greece to see whether BCG can increase resistance to infections overall in elderly people. He is planning to start a similar study in the Netherlands soon. The trial was designed before the new coronavirus emerged, but the pandemic may reveal BCG’s broad effects more clearly, Netea says.

For the health care worker study, Neeta teamed up with epidemiologist and microbiologist Marc Bonten of UMC Utrecht. “There is a lot of enthusiasm to participate,” among the workers, Bonten says. The team decided not to use actual infection with coronavirus as the study outcome, but “unplanned absenteeism.” “We don’t have a large budget and it won’t be feasible to visit the sick professionals at home,” Bonten says. Looking at absenteeism has the advantage that any beneficial effects of the BCG vaccine on influenza and other infections may be captured as well, he says.


[1] https://www.bandim.org/research

[2] https://www.who.int/immunization/sage/meetings/2014/april/3_NSE_Epidemiology_review_Report_to_SAGE_14_Mar_FINAL.pdf

[3] https://www.bmj.com/content/355/bmj.i5170


Post Comments(1)

Said3 years, 10 months ago

Some people say the most affected countries are the most democratic countries"transparent"!

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