Bacille Calmette-Guérin Vaccination in Infancy Does Not Protect Against Coronavirus Disease 2019 (COVID-19): Evidence From a Natural Experiment in Sweden

  1. Clément de Chaisemartin
  2. Luc de Chaisemartin

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Abstract

Background

The bacille Calmette-Guérin (BCG) tuberculosis vaccine has immunity benefits against respiratory infections. Accordingly, it has been hypothesized to have a protective effect against coronavirus disease 2019 (COVID-19). Recent research found that countries with universal BCG childhood vaccination policies tend to be less affected by the COVID-19 pandemic. However, such ecological studies are biased by numerous confounders. Instead, this paper reports on a rare nationwide natural experiment that occurred in Sweden in 1975, where discontinuation of newborns’ BCG vaccination led to a dramatic decrease in BCG coverage rate, thus allowing us to estimate BCG’s effect without the biases associated with cross-country comparisons.

Methods

Numbers of COVID-19 cases and hospitalizations were recorded for birth cohorts born just before and just after 1975, representing 1 026 304 and 1 018 544 individuals, respectively. We used regression discontinuity to assess the effect of BCG vaccination on COVID-19–related outcomes. On such a large population, this method allows for a precision that would be hard to achieve using a randomized controlled trial.

Results

The odds ratios (95% CI) for COVID-19 cases and COVID-19–related hospitalizations were 1.0005 (.8130–1.1881) and 1.2046 (.7532–1.6560), allowing us to reject fairly modest effects of universal BCG vaccination. We can reject with 95% confidence that universal BCG vaccination reduces the number of cases by 19% and the number of hospitalizations by 25%.

Conclusions

While the effect of a recent vaccination must be evaluated, we provide strong evidence that receiving the BCG vaccine at birth does not have a protective effect against COVID-19 among middle-aged individuals.

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  1. Version published to 10.1093/cid/ciaa1223
  2. ScreenIT

    SciScore for 10.1101/2020.06.22.20137802: (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 variablenot detected.

    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:
    This being said, there is a number of limitations to this work that one has to bear in mind. As in many other countries, Folkhälsomyndigheten’s cases count probably underestimates the true number of cases, because it only includes cases confirmed by a laboratory test. Its deaths count probably underestimates the true number of COVID-19 deaths as well, as it only includes deaths where a COVID-19 diagnosis has been confirmed during the past 30 days. However, these limitations are common to all studies on this question and are unlikely to affect much the results. Furthermore, RD estimates only apply to units close to the eligibility threshold. For instance, this study estimates the effect of universal BCG vaccination for individuals born around April 1st 1975, who are in their mid-forties during the COVID-19 pandemic. Even though some of the BCG protective effects tend to fade rather than increase over time19, it could still be the case that BCG vaccination at birth has larger effects against COVID-19 on older than middle-aged individuals. When it generalized BCG vaccination in the 1940s, Sweden simultaneously started vaccinating various age groups: newborns in 1943, children entering and leaving school in 1944, and military conscripts in 194520. BCG vaccination rates are not available for cohorts born in the 1930s and 1940s, but it seems likely that the vaccination rate increased gradually, so BCG introduction in Sweden does not lend itself to an RD analysis. There may be other...

    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.

  3. Version published to 10.1101/2020.06.22.20137802v1 on medRxiv