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In a recent study published in the PLOS ONE journal, researchers assessed the ecological association suggesting the efficacy of bacillus Calmette-Guerin (BCG) vaccination against coronavirus disease 2019 (COVID-19).

Study: Spurious early ecological association suggesting BCG vaccination effectiveness for COVID-19. Image Credit: LookerStudio/Shutterstock

Throughout the COVID-19 pandemic, researchers have considered the possibility of using existing preventive and therapeutic compounds such as the BCG vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One such study is a highly-cited published pre-print by Miller et al., which discovered that middle/high-income countries that never implemented a universal BCG policy showed a higher COVID-19 burden in comparison to countries that have universal BCG vaccination policies.

About the study

In the present study, researchers determined whether the early ecological results indicating that BCG appeared to protect against SARS-CoV-2 infection persisted in the later phases of the pandemic.

The team repeated the analysis performed by Miller et al. using the same statistical techniques to judge the reliability of their results for each month in 2020 after their analysis in March 2020. Those authors used COVID-19 data from Google News to analyze the association between BCG vaccination and COVID-19 morbidity and mortality from 1 January 2020 to 21 March 2020. The team used information on COVID-19 infection and mortality from the COVID-19 Data Repository at Johns Hopkins University.

The Miller et al. March 2020 dataset and the Johns Hopkins Repository March 2020 dataset were compared to assess the similarities of the results. The Hopkins Repository provided mortality and incidence counts that were, irbesartan patient reviews on average, 1.07 and 1.09 times higher for each country, respectively.

Like Miller et al., the team assessed three outcomes: per capita incidence, mortality, and the mortality-to-incidence ratio for COVID-19. Per capita, COVID-19 mortality and incidence was the number of COVID-19 fatalities and cases per 100,000 individuals. Additionally, like Miller et al., the team extracted information on national BCG vaccination policies from the BCG World Atlas for countries that: (1) had a total population of over a million individuals and (2) was classified as middle/high- or high-income countries according to World Bank categories.


Miller et al. investigated 55 middle/high- and high-income nations that had universal BCG vaccination policies in place, as well as five that had never had this policy. Wilcoxon Rank Sum Tests revealed that, as of March 2020, COVID-19 incidence, mortality, and mortality-to-incidence ratios were statistically significantly lower in countries with universal immunization programs than in those without such BCG regulations.

Initially, the researchers found that COVID-19 mortality rates in nations without a history of BCG policies remained much higher than those with current BCG policies, with the extent of this difference largely remaining consistent after May 2020. On the other hand, variations in COVID-19 occurrence between these groups were not statistically significant from May to October, but the variations achieved significance again in November and December. Statistically significant variations were evident for COVID-19 mortality-to-incidence ratios up until July but not beyond that.

Pearson correlation coefficients corresponding to the COVID-19 incidence rate and mortality-to-incidence ratio did not have any statistical significance for any period. However, the correlation coefficients were lower for all months as compared to that in March 2020 in the case of countries having current BCG policies. This indicated a statistically significant positive association between mortality rate and BCG vaccination in March 2020 but not thereafter.

Statistically significant data for incidence and mortality in March 2020 for nations with prior universal BCG vaccination regimes diminished by May and April 2020, respectively, and remained non-significant throughout the study period. The mortality-to-incidence ratio's correlation coefficient was never statistically significant. All correlation coefficients for all three outcomes were reduced every month following March 2020, with the exception of a slight rise in the correlation coefficient for incidence in April 2020 among nations that no longer have universal BCG programs.

Overall, the study findings showed that as the pandemic spread, the differences in COVID-19 burden related to BCG vaccination policies in March 2020 often declined in magnitude and typically lost statistical significance. The current study emphasizes the importance of exercising caution while assessing COVID-19 ecological analyses.

Journal reference:
  • Ledesma JR, Lurie P, Yorlets RR, Daly G, Chrysanthopoulou S, et al. (2022). Spurious early ecological association suggesting BCG vaccination effectiveness for COVID-19. PLOS ONE. doi: https://doi.org/10.1371/journal.pone.0274900 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0274900

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: BCG Vaccine, Coronavirus, Coronavirus Disease COVID-19, covid-19, Efficacy, Immunization, Mortality, Pandemic, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Vaccine

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Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.

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