Since identification of the new coronavirus in early January, scientists in universities and drug companies have been racing to develop a vaccine, with about 115 different candidates now in various stages of trials, according to Nature.com. But other researchers have taken a different tack, looking at existing vaccines developed for other infections to see if they might help the body’s immune system fight the disease now known as Covid-19. One that has attracted attention and several studies was developed about 100 years ago as a vaccine against tuberculosis. It’s known as BCG, short for Bacillus Calmette-Guérin, and some research indicates that countries that gave BCG to citizens in public inoculation programmes are reporting lower numbers of Covid-19 infections and deaths. The World Health Organisation and some scientists have cautioned that more evidence is needed to support this theory. However, the urgency forced by the pandemic and positive preliminary findings have encouraged researchers to pursue more trials. One study that showed a correlation between BCG vaccination and the incidence and fatality rates of Covid-19 was done by a team of infectious disease researchers and urologists from Ireland and the United States. Co-author Dr Paul Hegarty said the BCG vaccine already had uses beyond tuberculosis. It was given to people with bladder cancer as it had been found to delay the spread or recurrence of the disease. So the team decided to investigate if there could also be effects on Sars-CoV-2, the virus that causes Covid-19. BCG is one of the widest-deployed vaccines in the world, with a long history and solid safety record. Universal vaccination campaigns are common in the developing world. An exception is Ireland, which suspended its programme after 2015 because of a shortage of the vaccine. Other nations, such as Canada and the United States, either recommended BCG for high-risk groups or did not advocate national use of the vaccine, according to the BCG World Atlas database. Researchers grouped data on Covid-19 from 153 countries into two groups: those that had national BCG vaccination programmes and those that did not, based on the database. After accounting for differences such as the number of hospital beds in each country, the analysis showed that daily incidence of Covid-19 was 0.8 per million in countries with BCG vaccination compared to 34.8 per million in countries without. The coronavirus mutation that threatens the race to develop vaccine The crude case fatality rate – or proportion of deaths from cases – was 4.1 per cent in countries with BCG vaccination and 5.1 per cent in countries without, according to the research. “We were flabbergasted when we got this data and then we decided to look at country by country,” said Hegarty, who is also a medical consultant for the Mater Private Hospital in Dublin. “Every country we’ve looked at who’s had a BCG programme seems to have a much more favourable outcome.” Several other studies, published as preprints or research that has not been peer-reviewed, also found a similar correlation to that of Hegarty and his team. An analysis by vaccine researchers at Johns Hopkins Bloomberg School of Public Health showed the Covid-19 mortality rate in countries using BCG was 5.8 times lower than countries with no national BCG vaccination campaign. While Hegarty’s analysis returned positive findings and the study is scheduled to be published in the European Urology Oncology journal, he said more needed to be done to substantiate the theory. “At the moment this is an observation and that’s all it is. It’s hypothesis-generating,” he said. Green light for human trials on more China Covid-19 vaccine hopefuls Randomised trials tracking medical workers who are given the BCG vaccine and are exposed to Sars-CoV-2 are under way. Hegarty’s colleagues are involved in a US trial that may be expanded to Ireland and Britain. Results from these trials would provide evidence that ecological or national-level studies could not, according to tuberculosis researcher Dr Madhukar Pai from McGill University in Canada. Pai was part of the team that developed the BCG World Atlas database used for ecological studies on BCG vaccination and Covid-19. “The biggest limitation is that the ecological design does not permit us to make any inference to individuals, and aggregate trends could easily be confounded by other variables that are not easy to control for. Randomisation is the surest way to eliminate the influence of extraneous factors,” Pai said. The coronavirus testing capacity of different countries, as well as demographics and gender, all could have influenced the findings, he said. “I am all for further research on the BCG hypothesis but I would not recommend any public health or clinical action on the basis of what evidence we currently have.” Researchers are looking at vaccines other than BCG for indications that they may help protect patients against Covid-19. Dr Robert Gallo, a virologist who helped discover the human immunodeficiency virus (HIV) that causes Aids, said he was leading a project to use the oral polio vaccine for possible short-term coronavirus treatment. Previous research suggested the polio vaccine activated a temporary immunity in people that protected against RNA viruses such as influenza. The hope is that a similar short-term immunity could be generated for the coronavirus, also an RNA strain, according to an interview that Gallo gave PBS. “If I were betting, I’d bet pretty strongly that this is going to really help. So I want to get moving fast on it,” Gallo said. Researchers from the University of Cambridge in Britain studied MMR, the vaccine for measles, mumps and rubella. They found that the rubella virus and Sars-CoV-2 shared 29 per cent similarity in amino acid sequence identity. Bug in the system: why there’s no quick fix for a Covid-19 vaccine This indicates that immunity generated by the rubella vaccine could also provide protection against the coronavirus, according to the researchers. The team also studied data from Covid-19 patients admitted to a British hospital to assess the level of rubella antibodies and the severity of their sickness. They found that rubella vaccination seemed to have improved outcomes for Covid-19 patients, according to a non-peer-reviewed preprint paper the team published. “Taken together, we suggest that MMR will not prevent Covid-19 infection but could potentially reduce poor outcomes,” the paper said. Again, other specialists in the field stressed that more research was needed. Ashley St John, an immunologist from Duke-National University of Singapore Medical School, said BCG vaccines were given when people were young to prevent tuberculosis, a bacterial infection . It was different to a virus, the cause of Covid-19. “You're talking about comparing an immune response to a bacteria and assuming that it's going to be somehow protective against the virus. That is a little bit difficult to understand how it could be beneficial,” she said. However, immediately after vaccination, there was an effect called cross-protection. “Immediately following a successful vaccine, you have a burst of antibodies that are specific and non-specific and some of those non-specific antibodies could potentially neutralise other pathogens. That is the goal of the immune system, to cast a wide net early in our response,” St John said. So the randomised trials on BCG vaccines and Covid-19 could show there was an enhanced immune response, even towards a different pathogen. But any positive effect of the BCG vaccine on a pathogen did not mean there should be a large-scale vaccine campaign in the community and the two issues should not be confused, St John said. Ultimately, Hegarty said, the goal was to help high-risk groups such as medical workers and the elderly be protected against Covid-19 while a targeted vaccine against the coronavirus was being developed. “If there is a reliable [coronavirus] vaccine at that stage, then this is no longer relevant,” he said.