Association between live childhood vaccines and COVID-19 outcomes: a national-level analysis

  1. Chikara Ogimi
  2. Pingping Qu
  3. Michael Boeckh
  4. Rachel A. Bender Ignacio
  5. Sahar Z. Zangeneh

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Abstract

We investigated whether countries with higher coverage of childhood live vaccines [BCG or measles-containing-vaccine (MCV)] have reduced risk of coronavirus disease 2019 (COVID-19)-related mortality, while accounting for known systems differences between countries. In this ecological study of 140 countries using publicly available national-level data, higher vaccine coverage, representing estimated proportion of people vaccinated during the last 14 years, was associated with lower COVID-19 deaths. The associations attenuated for both vaccine variables, and MCV coverage became no longer significant once adjusted for published estimates of the Healthcare access and quality index (HAQI), a validated summary score of healthcare quality indicators. The magnitude of association between BCG coverage and COVID-19 death rate varied according to HAQI, and MCV coverage had little effect on the association between BCG and COVID-19 deaths. While there are associations between live vaccine coverage and COVID-19 outcomes, the vaccine coverage variables themselves were strongly correlated with COVID-19 testing rate, HAQI and life expectancy. This suggests that the population-level associations may be further confounded by differences in structural health systems and policies. Cluster randomised studies of booster vaccines would be ideal to evaluate the efficacy of trained immunity in preventing COVID-19 infections and mortality in vaccinated populations and on community transmission.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.17.20214510: (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:
    We explicitly acknowledge the principal limitation that country-level data does not represent individual exposures or outcomes [22]. There are other potential confounders such as genetic variance, national COVID-19-specific public health responses (e.g. percent mask use, policy and adherence to movement restrictions), heterogeneity in population density and disparities in access to care, the majority of which are difficult to quantify [5, 21, 23]. Although studies have indicated certain BCG strains might induce more effective trained immunity than others, there was insufficient data to evaluate these hypotheses [3, 24]. Moreover, our analysis treated the national-level summaries as fixed variables, ignoring the uncertainty in these estimates and possibly their biases. The p-values reported in Table 2 are thus under-estimates of the true p-values. Finally, our models only examined linear associations. In conclusion, we found an association between higher cumulative BCG coverage and COVID-19 related deaths but not cases, and only a marginal effect of MCV coverage on either; we cannot rule out that these observations are attributable to differential healthcare infrastructure, including COVID-19 testing rate and population age distribution or other unmeasured confounders. Several RCTs (primarily BCG) are currently underway (https://clinicaltrials.gov/) to evaluate the impact of live pathogen vaccines on COVID-19 related outcomes. Some of them may however not be able to adequately...

    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

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  2. Version published to 10.1017/s0950268821000571
  3. Version published to 10.1101/2020.10.17.20214510 on medRxiv