As scientists race to make a new vaccine against covid-19, some are touting a century-old one as a possible stopgap.
The vaccine is BCG (Bacillus Calmette-Guérin), which protects against tuberculosis (TB). In countries with routine BCG vaccination, the pandemic appears to be less severe. Advocates of BCG say this could be because the vaccine is a general immune-system enhancer – a long-standing but unproven hypothesis. But critics say we can’t be sure.
BCG has been used since 1921. It contains a live bacterium related to the one that causes TB, and the World Health Organization recommends it in countries with high levels of the disease. Most countries – including China, where the coronavirus outbreak began – . But some, including the US and Italy, have never had one and others phased it out as TB became less of a concern – the UK stopped routine vaccination in schools in 2005.
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The vaccine was already being updated but the covid-19 pandemic has given it a booster shot. In March, the Max Planck Institute for Infection Biology in Berlin for a clinical trial of a genetically modified version of BCG, VPM1002, against the covid-19 coronavirus. Its rationale was that the vaccine has been shown to make mice more resistant to viruses including flu and herpes.
The trial has been given regulatory approval and should start before the end of the month. If it succeeds, millions of doses could be made available in a very short time, says Adar Poonawalla of the Serum Institute of India, a private company that is partnering with the Max Planck to develop the vaccine.
A second has already begun in the Netherlands, which will test whether the vaccine reduces absenteeism among healthcare workers for any reason including illness. The Netherlands doesn’t vaccinate with BCG so most healthcare workers won’t have had it. The trial is due to be completed in December. A is under way in Australia, with preliminary results due in October, though the full trial will run until March 2022.
On the theoretical side, a number of non-peer-reviewed papers have been published pointing out that countries where the BCG vaccine is used have fewer covid-19 cases and/or deaths. Gonzalo Otazu of New York Institute of Technology, author of the , says he was alerted by the difference between Italy, which doesn’t vaccinate, and Japan, which does. He then did a global analysis based on the , which has up-to-date information on BCG programmes.
“The correlation was very clear,” he says. But he cautions that it is too early to recommend action. “BCG vaccination is a potential new tool in the fight against covid-19, but we have to wait for the results of the ongoing clinical trials,” he says.
Papers have also appeared that the correlation doesn’t imply causation. The . “Such studies are prone to significant bias from many confounders,” it writes, “including differences in national demographics and disease burden, testing rates… and the stage of the pandemic in each country…. There is no evidence that [BCG] protects people against infection with COVID-19 virus. In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19.”
Lone Graff Stensballe, a BCG expert at the Danish National University Hospital who didn’t contribute to any of the papers, is also sceptical, both of the general claims for BCG and the specific claims about covid-19. “It has not been possible to detect such beneficial non-specific effects of BCG in well-designed studies,” she says. “My advice would be to invest our scarce resources in other preventive measures.”
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Article amended on 24 April 2020
We corrected Gonzalo Otazu’s affiliation
