Differential COVID-19-attributable mortality and BCG vaccine use in countries

  1. Anita Shet
  2. Debashree Ray
  3. Neelika Malavige
  4. Mathuram Santosham
  5. Naor Bar-Zeev

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Abstract

While mortality attributable to COVID-19 has devastated global health systems and economies, striking regional differences have been observed. The Bacille Calmette Guérin (BCG) vaccine has previously been shown to have non-specific protective effects on infections, as well as long-term efficacy against tuberculosis. Using publicly available data we built a simple log-linear regression model to assess the association of BCG use and COVID-19-attributable mortality per 1 million population after adjusting for confounders including country economic status (GDP per capita), and proportion of elderly among the population. The timing of country entry into the pandemic epidemiological trajectory was aligned by plotting time since the 100 th reported case. Countries with economies classified as lower-middle-income, upper-middle-income and high-income countries (LMIC, UMIC, HIC) had median crude COVID-19 log-mortality of 0.4 (Interquartile Range (IQR) 0.1, 0.4), 0.7 (IQR 0.2, 2.2) and 5.5 (IQR 1.6, 13.9), respectively. COVID-19-attributable mortality among BCG-using countries was 5.8 times lower [95% CI 1.8-19.0] than in non BCG-using countries. Notwithstanding limitations due to testing constraints in LMICs, case ascertainment bias and a plausible rise of cases as countries progress along the epidemiological trajectory, these analyses provide intriguing observations that urgently warrant mobilization of resources for prospective randomized interventional studies and institution of systematic disease surveillance, particularly in LMICs.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.01.20049478: (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:
    The limitations in our analyses are important to consider. Deaths lag behind symptomatic infection by 2-8 weeks, and when compared with concurrent incidence cases may underestimate the CFR, although this is less likely to influence cumulative crude mortality32. Health system preparedness of each country and the institution of control measures such as social distancing and lockdowns can also determine the cases and mortality numbers. Our data are not meant to falsely reassure countries that their use of BCG may lead to lower mortality. Indeed, our analysis is ecological, does not take into account present BCG coverage, nor timing of BCG vaccine introduction into national schedules, and is not based on a randomized comparison. By far the most important source of unmeasured confounding in our analysis relates to differential testing and reporting. Limited laboratory surveillance availability and access to facility-based care is common in countries using BCG. Substantial case underascertainment or under-reporting of deaths can magnify any association between mortality and BCG use. In exponential functions, small iterations in time result in substantial changes in outcome. Our findings need to be interpreted with caution; given vulnerable health systems and high levels of comorbidities in LMICs, if an exponential rise of cases followed by deaths were to occur in ensuing weeks, this would alter the epidemiological predictions in this report. Despite all these caveats, the inverse r...

    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 10.1101/2020.04.01.20049478v1 on medRxiv