A shred of evidence that BCG vaccine may protect against COVID-19: Comparing cohorts in Spain and Italy

  1. David I. Levine

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Abstract

There is evidence that the BCG vaccine against tuberculosis also helps prevent other diseases – perhaps including COVD-19. Spain had a program for universal BCG vaccination until 1981.

Objective

To see whether cohorts born when Spain had a program of universal BCG vaccination had lower rates of confirmed cases of COVID-19 and mortality (relative to similar cohorts in Italy).

Methods

We compare COVID-19 mortality and confirmed cases for those born roughly a decade before and after 1981. We compare the outcomes to the same age cohorts in Italy, which never had universal BCG vaccination.

Results

The Spanish cohort that received BCG had a relative risk of 0.962 of having a confirmed case of COVID-19. This risk is statistically significantly below unity (95% CI 0.952 to 0.972, P< 0.001). There is also suggestive evidence the BCG cohort in Spain had lower mortality (relative risk 0.929, CI 0.850 to 1.01, P = 0.11). The small sample size makes this test underpowered.

Conclusion

These suggestive results provide a shred of evidence that BCG vaccinations help protect against COVID. I outline many limitations to this study and point how better data can help be more convincing.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.05.20123539: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableIn both nations, mortality is higher is higher for men than for women.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: Interpretation of the effect sizes is easiest if no Spaniards in their thirties and no Italians received BCG vaccination, while 100% or Spaniards in their forties did. Those assumptions do not hold. For example, migrants received BCG based on their childhood location. Spain never reached 100% coverage of BCG. The 1981 stopping date of BCG in Spain implies some people in their late 30s in February through April 2020 received BCG as children, but are part of the “thirties” (non-BCG) cohort in this analysis. As noted above, Catalonia and the Basque Region ended their BCG programs at different years than the national program (1974 and 2013, respectively). In addition, Italy and post-1981 Spain never strove for 0% BCG coverage. High-risk groups were immunized in all of Italy, and some Italian regions had protocols for widespread BCG. This fuzziness will tend to bias down the estimated effects of BCG on COVID outcomes. The interpretation of the gap as causal is biased down because lower infections among those in their 40s will help protect those in the younger age group. That is, there are positive spillovers from the treatment group (those with BCG immunization) to the control group (nearby people without BCG).19 In addition, the ten-year window for comparison groups leaves room for omitted factors to affect the outcome. For example, we were able to do a coarse adjustment for differences in the age distribution. In addition, the relationship of risk factors such as he...

    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.

    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 checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.06.05.20123539v1 on medRxiv