Race for treatments: BCG, really?

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Epidemiological studies suggest that the world's oldest vaccine, BCG, used against tuberculosis, may reduce the risk of coronavirus infection as well as the risk of severe forms of Covid-19 disease. Professor Camille Locht, INSERM research director at the Pasteur Institute of Lille, is currently working with his team to set up a randomized controlled clinical trial to evaluate the interest of this option.

Could the old BCG (Bacille de Calmette et Guérin) be protective against Covid-19? This is the oldest tuberculosis vaccine in the world; it has been around for a hundred years and has been inoculated into more than three billion people worldwide. It is a very well-documented vaccine, and numerous studies on its rare contraindications have been carried out. Finally, it is one of the cheapest vaccines in the world.

Epidemiological studies have interestingly shown a correlation between BCG vaccination rates and Covid-19 morbidity and mortality rates. While the majority of these studies point in the same direction, " they do not suggest a causal relationship "says theInserm in a communiqué, as they remain subject to significant biases, particularly with regard to the difference in living standards and health policy between countries with high and low immunization rates.

However, BCG has previously shown a non-specific protective effect in children against infections, especially respiratory infections. Live vaccines such as BCG, the measles vaccine or the oral polio vaccine have been shown to have non-specific beneficial effects on certain infections. « It has been known for decades that BCG has non-specific beneficial effects It protects against diseases other than the one for which it was created, tuberculosis," Camille Locht told AFP.

Children vaccinated with BCG suffer less from other respiratory diseases; it is used to treat some bladder cancers and may protect against asthma and autoimmune diseases such as type 1 diabetes. The hypothesis is that the tuberculosis vaccine could have a similar effect against coronavirus, either by decreasing the risk of being infected or by limiting the severity of symptoms. In France, BCG was mandatory until 2007, but the protective effect of this vaccination decreases over time. This may be one of the reasons why children are less affected by the coronavirus than adults. Conversely, advances The Physician's DailyIn the case of the elderly, who may have been vaccinated a long time ago, this protective effect would no longer apply.

Hyperinflammatory storm

BCG could thus help reduce the extent of infection with the SARS-CoV-2 virus by stimulating the memory of innate immunity, the first immunity to come into play in the face of infection, and thus inducing "innate trained immunity". In the case of Covid-19, in addition to infection with the virus, in severe forms an excessive immune response occurs with the uncontrolled production of pro-inflammatory proteins, the cytokines. Doctors refer to these as "cytokine storms".

" Evidence is accumulating to suggest that a proportion of patients with severe forms of Covid-19 are subject to cytokine shock syndrome.e" writes, with British colleagues, Jessica Manson, a specialist in inflammatory phenomena at University College Hospital in London, in the medical journal "The Inflammatory Phenomena of the University College Hospital in London". The Lancet. This phenomenon of "hyper-inflammatory storm" has been identified to explain the dangerousness of respiratory diseases caused by coronaviruses.

Cytokines are substances naturally produced by the cells of the immune system to regulate immune action, in particular to promote the inflammatory reaction which is a natural defence response of an attacked organism. But in the case of the "cytokine storm", we observe a runaway of this system which leads to a hyper-inflammatory reaction that can become lethal.

" I think an exuberant immune response is what really kills patients (from Covid-19, editor's note) by destroying tissue. But it's not a certainty ", an expert from the University of Iowa told AFP.

" Vaccination, particularly BCG, may help to better orchestrate this inflammatory immune response. "explains to our confreres of Futura Health Laurent Lagrost, Inserm research director who is working on these links between inflammation and the immune system. The vaccine acts as a " military exercise in peacetime [to] fight the enemy effectively in wartime ", he stressed in an interview with BFMTV.

On the basis of these observations, researchers in several countries have launched large-scale clinical trials (1,000 people in the Netherlands, 4,000 in Australia) among people at high risk of exposure (health care personnel in particular).

France is also working on the subject. Camille Locht is preparing to set up a French double-blind clinical trial. Collaboration with Spain, which is also conducting research on a project of this type, could make it possible to compare the benefits of BCG vaccination on a large scale with a placebo common to both countries. However, if the clinical trial goes ahead, participants will still need to be followed for another 2-3 months to have reliable data.

Researchers are cautious: the BCG vaccine is a very interesting possibility, but it needs to be explored in rigorous clinical trials. To date, there are no data to recommend BCG vaccination to protect against Covid-19.

Sources: Inserm, AFP