Association of BCG vaccination policy and tuberculosis burden with incidence and mortality of COVID-19
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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.
Article activity feed
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SciScore for 10.1101/2020.03.30.20048165: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:We must discuss the limitation to interpret the present findings. A serious limitation is that we only conducted an ecological study, which does not exclude the effect of unknown confounding factors. We cannot determine the definitive causality link. Future clinical trials that manipulate the potential confounding variables can test causality. Individual-level epidemiological studies that examine individual history of BCG vaccination …
SciScore for 10.1101/2020.03.30.20048165: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:We must discuss the limitation to interpret the present findings. A serious limitation is that we only conducted an ecological study, which does not exclude the effect of unknown confounding factors. We cannot determine the definitive causality link. Future clinical trials that manipulate the potential confounding variables can test causality. Individual-level epidemiological studies that examine individual history of BCG vaccination and TB infection would also contribute to testing this hypothesis. Tuberculosis and other infectious diseases: Because BCG is an attenuated version of the bacterium causing TB, it is biologically plausible to assume that experience of TB infection itself may have a protective effect against COVID-19. About 80% of people in many Asian and African countries test positive, while 5–10% of people in the United States population test positive in the tuberculin test44. These numbers are consistent with our findings: high burden countries, many of which are in Africa and Asia, show low COVID-19 indices, even at this stage (April 26th). There are 53 high TB burden countries and regions, and, surprisingly, in the top 50 countries/regions among 142 in terms of the number of deaths per 1M population, we found only three high TB burden countries (Table S1). High TB burden countries are mostly countries with low income, which is, in fact, counter-intuitive, considering that low-income countries generally suffer from low hygiene and low medical care. Obviously,...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.03.30.20048165: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Scatter plot of total cases per one million population by community mobility change from baseline based on COVID-19 community mobility reports by Google. Googlesuggested: (Google, SCR_017097)Results from OddPub: Thank you for sharing your data.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for …
SciScore for 10.1101/2020.03.30.20048165: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Scatter plot of total cases per one million population by community mobility change from baseline based on COVID-19 community mobility reports by Google. Googlesuggested: (Google, SCR_017097)Results from OddPub: Thank you for sharing your data.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.
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