Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study

Discussion from original article

    We have shown epidemiological evidence indicating that some of the differences in morbidity and
mortality produced by COVID-19 across countries might be partially explained by a country’s BCG
vaccination policy. Italy, where the COVID 19 mortality is very high, never implemented universal
BCG vaccination. On the other hand, Japan had one of the early cases of COVID-19 but it has
maintained a low mortality rate despite not implementing the most strict forms of social isolation.
Japan have been implementing BCG vaccination since 1947. Iran had also been heavily hit by
COVID-19 and it started its universal BCG vaccination policy only in 1984 potentially leaving
anybody over 36 years old unprotected.
    Why did COVID-19 spread in China despite having a universal BCG policy since the 1950’s?
During the Cultural Revolution (1966-1976), tuberculosis prevention and treatment agencies were
disbanded and weakened. We speculate that this could have created a pool of potential hosts
that would be affected by and spread COVID-19. Currently, however, the situation in China seems
to be improving.

    Our data suggests that BCG vaccination seem to significantly reduce mortality associated with
COVID-19. We also found that the earlier that a country established a BCG vaccination policy,
the stronger the reduction in their number of deaths per million inhabitants, consistent with the
idea that protecting the elderly population might be crucial in reducing mortality. However, there
is still not proof that BCG inoculation at old age would boost defenses in elderly humans, but it
seems to do so in Guinea pigs against M. tuberculosis.
    BCG vaccination has been shown to produce broad protection against viral infections and sepsis,
raising the possibility that the protective effect of BCG might be not directly related to actions on
COVID-19 but on associated co-occurring infections or sepsis. However, we also found that BCG
vaccination was correlated with a reduction in the number of COVID-19 reported infections in a
country suggesting that BCG might confer some protection specifically against COVID-19. The
broad use of the BCG vaccine across a population could reduce the number of carriers, and
combined with other measures could act to slow down or stop the spread of COVID-19.
    Different countries use different BCG vaccination schedules, as well as different strains of the
bacteria. We have not divided the data depending on the strain used to determine which strains
are better at stopping spread of infection, as well as reducing mortality in the elderly population.
As each country used the same strain for the whole population, difference in strains for different
purposes should be gathered in randomized control trials with different subjects from the same
population tested with different strains.

    USA and other countries like Italy without a universal vaccination policy but with high fraction of
immigrants from countries with different universal BCG policies and using different strains offer
the possibility to perform epidemiological studies to determine vaccination schedules and strains
that would optimize protection against COVID-19.
    The correlation between the beginning of universal BCG vaccination and the protection against
COVID-19 suggests that BCG might confer long-lasting protection against the current strain of
coronavirus. However, randomized controlled trials using BCG are required to determine how fast
an immune response develops that protects against COVID-19. BCG is generally innocuous with
the main side effect the development of inflammation at the site of injection. However, BCG is
contraindicated in immune compromised people as well as pregnant women, so care should be
taken when applying these possible intervention for COVID-19.