Association of BCG vaccination policy and tuberculosis burden with incidence and mortality of COVID-19
View ORCID ProfileGiovanni Sala, View ORCID ProfileRik Chakraborti, View ORCID ProfileAtsuhiko Ota, View ORCID ProfileTsuyoshi Miyakawa
doi: https://doi.org/10.1101/2020.03.30.20048165
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Abstract
Background: Evidence suggests non-specific benefits of the tuberculosis vaccine bacillus Calmette-Guérin (BCG) against non-related infections. Recent studies propose such protection may extend to the novel COVID-19 as well. This is a contested hypothesis. Methods: Our ecological study confronts this hypothesis. We examine the effects of BCG vaccination on countries′ COVID-19 (a) cases and deaths (per million) and (b) exponential growth factors over specific periods of the pandemic. Since the BCG vaccine was derived from Mycobacterium bovis, a bacterium causing tuberculosis in cattle, having suffered from tuberculosis also may exert a non-specific protection against the COVID-19 as well. Along with BCG vaccination, we test the effect of the prevalence of tuberculosis. We employ multiple regression and principal component analysis (PCA) to control for potentially confounding variables (n = 16). Results: BCG vaccination policy and incidence of tuberculosis is associated with a reduction in both COVID-19 cases and deaths, and the effects of these two variables are additive (≈ 5% to 15% of total unique variance explained). The study of exponential growth factors in the initial stages of the pandemic further shows that BCG vaccination exerts a significant effect (up to 35% of unique variance explained). Conclusions: Overall, these findings corroborate the hypothesis that BCG vaccination and exposure to tuberculosis may induce a non-specific protection against the novel SARS-CoV-2 infection, even after accounting for a large number of confounding influences. However, given the potential public-health benefits, our results indicate that the hypothesis deserves further attention and should not be hastily dismissed.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
The authors report that no external funding was received.
Author Declarations
All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.
Yes
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Thanks, everyone, for your precious comments.
1. We are examining the potential confounders, which includes the ones mentioned here.
2. As Rosemary mentioned, BCG is an attenuated version TB and, indeed, big protective effect of TB prevalence against COVID-19 exists. We will incorporate the data in the next version.
3. We obtained the data from the web site of European Centre for Disease Prevention and Control, and are re-analyzing the growth of spreading in a more quantitive manner. Basically, there are significant effects of BCG/TB against COVID-19 growth, which will replace the data shown in Figure 3.
4. Regarding the tourists from China, according to a survey, the top 10 destination countries of China’s out bound countries are Japan, Thailand, South Korea, Indonesia, Singapore, Malaysia, Australia, UK, New Zealand, and Maldives, and 9 out of 10 of them are the ones with extremely low COVID-19 cases and deaths (4 or lower deaths per million) , as of April 13th, which makes it unlikely that the Traveling activity from China matters. This will be added to the discussion. Also, we evaluated the number of international arrivals in each country and it did not essentially affect the results (almost at all).
5. As for masks and green tea, they cannot explain 1) the differences between Eastern Europe and Western Europe and 2) low COVID-19 indices in Africa, South America and South East Asia. We may consider their potential effect, once we can get any good statistics representing those things, but so far, we set priority low for these potential confounders.
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Anyway, we will upload next version sometime in next week and it will be appreciated if you could keep providing us critical comments, which will greatly improve our manuscript. Thank you!
