Cough, tiredness, exhaustion, fever – what sounds like a list of common symptoms of COVID-19, but also applies to another infectious disease: tuberculosis. Tuberculosis bacteria often infect the lungs, but also other organs and can cause serious illnesses. However, the disease often does not break out. The Robert Koch Institute (RKI) registered 4,127 tuberculosis cases in Germany in 2020 (an incidence of 5 new cases per 100,000 inhabitants).
On the other hand, the situation is different worldwide: 7.1 million tuberculosis cases were diagnosed Global Tuberculosis Report by the WHO for 2019. About 1.2 million of them died from it. People most commonly affected by tuberculosis are in India, Indonesia, China, the Philippines, Bangladesh, Nigeria, Pakistan and South Africa. But this potentially fatal disease in particular seems to have a bizarre side effect, as researchers have now discovered.
mice that fighting tuberculosis infection appear protected against COVID-19. This is what Richard Robinson from the Ohio State University writes together with colleagues in the specialist journal PLOS pathogens. The team had first infected the rodents with tuberculosis and four weeks later exposed them to the alpha variant of Sars-CoV-2. “We expected the animals to get worse with the second infection, but that wasn’t the case,” says Robinson. What’s more, they seemed to have become resistant to COVID-19.
This effect was evident both in wild-type mice and in genetically modified conspecifics that can form the human ACE-2 receptor – the docking site for Sars-CoV-2. The latter could therefore be expected to be more susceptible to COVID-19. However, it seems that the immune response to tuberculosis also offers protection against the establishment of the coronavirus.
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In search of the clever immune cell group
The researchers found increased amounts of B and T cells in the blood of the test animals, which are responsible for antibody production and other defense functions such as destroying infected cells. The researchers want to find out in further experiments how exactly the cross-pathogen protection works. In order to find out which immune cells play a role in this, they want to use further mouse experiments to examine what happens when they suppress individual immune cell groups one after the other. If the protection suddenly stops working, the type of cell that has been eliminated plays a key role.
Robinson points out some limitations of the results, especially since there are – as very often – differences between the physiology of experimental animals and humans. Mice, for example, do not show the full spectrum of tuberculosis disease symptoms and develop the disease less frequently than the 10 percent of infected humans. “However, mice are well suited for clarifying the question of which immune response brings the pathogens under control,” says Robinson.
Last but not least, Robinson’s team also wants to find out whether the effect also occurs in humans and whether it can confirm the similar indications that have been collected so far. Because there are already initial indications from studies that have examined the effects of the tuberculosis vaccination – not just the illness itself. For example, researchers led by Martha Berg from the University of Michigan presented results from more than 100 countries in May 2020 Covid-19 spread more slowly and death rates increased more slowly in those countries where vaccination against tuberculosis was compulsory.
In addition, it was observed much earlier that the tuberculosis vaccination with the so-called Bacillus Calmette-Guérin (BCG) not only seemed to offer general, broad-based protection with a faster immune response against various infections. These include respiratory diseases in particular, but also other infections such as yellow fever. The protection is probably based on an unusual mechanism.
Tuberculosis vaccination could offer broader protection
Normally, in many cases, the innate immune system keeps the gate clean and catches pathogens before they can cause an infection. However, this defensive arm does not remember its enemies and can therefore be taken by surprise. It is then up to the acquired defenses to break down the invading germs and use the fragments to stimulate the formation of suitable antibodies – in order to be able to react more quickly the next time you encounter them.
However, the BCG vaccine now seems to equip the innate defenses that kick in first with a kind of immune memory. The weakened bacterium forming the vaccine triggers corresponding epigenetic changes in the cells of the innate defense, ie changes that do not change the DNA itself, but rather the pattern of the molecular caps on it. These caps determine, for example, which genes are transcribed and which are not. The altered epigenetic pattern seems to ensure that more cytokines, the inflammatory messengers of the immune system, are released in response to pathogens.
Two large phase 3 trials started in 2020 were designed to test how well the new BCG vaccine VPM1002 works against COVID-19. The vaccine was developed at the Max Planck Institute for Infection Biology and is a genetically engineered advancement of the original BCG vaccine. The first results should be available in May. The big question is whether the vaccine alone provides good protection against COVID-19. Even if not, Robinson hopes that BCG vaccines could at least enhance the effect of previous COVID vaccines. He would also like to check this with his animal models.