There is evidence that another BCG vaccination could protect against Covid-19. The latest results come from a Greek study that was classified as a preprint that has not yet been peer-reviewed. has been published medRxiv.

BCG – Bacillus Calmette – Guérin – celebrates its 100th anniversary this summer and remains the only approved vaccine against tuberculosis. Developed by the French bacteriologists Albert Calmette and Camille Guérin from a cattle relative of Mycobacterium tuberculosis, it wasfirst administered to an infant in a Paris hospital in July 1921.

It was recognized early that BCG vaccination appeared to reduce deaths from disease beyond just tuberculosis. Immunologists have long suspected that this live vaccine stimulates the immune system to fight infections better. Last year it was hypothesized that the BCG vaccination could protect against Covid-19.

The Greek preprint – which has yet to be reviewed by experts – reported that BCG revaccination resulted in a 68% risk reduction for Covid-19 infection, which has been clinically or virologically confirmed. Five patients who received a placebo developed severe illness, but only one in the BCG vaccine group. However, the study was relatively small with only about 300 volunteers. “It’s interesting data, but a small study with a high loss of follow-up,” says Frederik Schaltz-Buchholzer, epidemiologist at the University of Southern Denmark who is involved in the Danish BCG studies. “We shouldn’t be opening champagne bottles just yet. We still have a lot of trials going on. ‘

Data from large studies of BCG revaccination in medical personnel are now in progress. In January, however, a Dutch study with 6,132 patients drew attention to initial findings that the vaccine did not protect the elderly against Covid-19 symptoms.

Immunologist Mihai Netea, who was involved in the Greek and Dutch studies, says an important difference between them could be that older Greeks received the BCG vaccine as children, while people in countries like Italy, the Netherlands and Belgium never received one. “It could be that the T-cell response is different in those previously exposed to BCG, and that the innate immune response is enhanced by a second administration,” says Netea, who led studies that showed BCG the immune system reprogrammes cells.

Major BCG studies for Covid are ongoing

Most of the BCG studies worldwide for Covid-19 are among healthcare workers with more than 2500 volunteers in Brazil. These are part of the Brace study, which recruited over 7,500 healthcare workers at 34 locations in Brazil, the Netherlands, Spain, the UK and Australia. This study is led by Nigel Curtis, a vaccine scientist at Murdoch Children’s Research Institute and the University of Melbourne, Australia, with support from the Bill & Melinda Gates Foundation. The main question is whether BCG’s off-target effects boost innate immunity, thereby reducing the severity of Covid-19, Curtis says.

There is also a study in Denmark with over 1200 health care workers and a study with older volunteers who are still being recruited there. The earlier study was stopped prematurely because health care workers started receiving Covid-19 vaccines. This is an issue with other BCG studies conducted in Europe and the United States where study participants were eligible for Sars-CoV-2 vaccines. Epidemiologists from Utrecht University Hospital, Netherlands, have now invited BCG studies to a meta-analysis. The aim is to increase statistical power by combining the data from all ongoing studies now instead of waiting for the studies to be completed, explains the immunologist Henri van Werkhoven in Utrecht.

BCG is not the only live vaccine currently being evaluated. Washington University School of Medicine in St. Louis is coordinating an international study to see if the measles, mumps, and rubella (MMR) vaccine protects healthcare workers from Sars-CoV-2. A current observational study from India also suggests that immunotherapy with killed mycobacteria reduced hospital admissions due to Covid-19.

“Another BCG vaccination in countries with high pressure loads can be useful in countries where classic vaccines are not available. In order to finally prove this, larger studies from developing countries would of course be necessary, ”comments Netea. BCG’s production would also have to be ramped up.

These results will be important for future pandemics “to get even partial protection from the start so that you don’t have to close economies and have so much suffering,” says Netea. He adds that fortunately we “have other vaccines that are much more effective”. [for Covid-19] ’So the effort should be put into there’.

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