Table 4 Effects of BCG vaccination on morbidity and mortality based on association and confounding variables

Escobar et al. (2020) [25]

Multiple linear regression

Stage of COVID-19 pandemic

Development

Rurality

Population density

Age structure

Inverse association between BCG vaccination and COVID-19 mortality after controlling for confounding variables

de Chaisemartin and de Chaisemartin (2021) [26]

Regression discontinuity

None reported due to cohort design, no variable cross-country comparisons

Universal BCG policy has no effect on COVID-19 cases, hospitalizations, and deaths per 1000 inhabitants

Chimoyi et al. (2020) [27]

Log-linear regression

GDP per capita

Population size

Population > 65 years

Tests per capita

Stringency level at 100th case

Smoking prevalence

Difference between date of 100th case and end of May 2020

No significant association between BCG status and cases and deaths even when adjusted for different time points

Positive association seen in population size, population > 65 years, and tests per capita

Wickramasinghe et al. (2020) [28]

Linear regression

Income level

Income status had a statistically significant effect on caseload; universal BCG vaccination policy had a significant inverse effect

Szigeti et al. (2020) [29]

Multiple regression

Historic colonization status

Median age

Urban population percentage

Population density

Air passengers

Deaths per million as dependent variable: BCG vaccination was statistically significant

Deaths per case as dependent variable:

BCG vaccination was non-significant

‘Historic colonization status’, median age were statistically significant

Berg et al. (2020) [31]

Linear mixed effect model

Cultural dimensions

Individualism versus collectivism

Power distance

Countries with BCG vaccination policy until at least 2000 had significantly slower growth rate of COVID-19

Significantly lower growth rate of COVID-19 deaths in countries with BCG vaccinations until at least 2000

Ogimi et al. (2021) [32]

Nested linear model

Measles vaccine coverage (MCV)

Healthcare Access and Quality Index (HAQI)

Life expectancy

Number of hospital beds

Physicians per population

GDP

BCG was marginally associated with lower COVID-19 death rates. Increased association between BCG and COVID-19 as a function of HAQI

MCV was also associated with lower COVID-19 deaths, but no significant association when adjusted for HAQI

Ebina-Shibuya et al. (2020) [33]

Multiple regression

Gross national income,

Life expectancy at birth

Infant mortality at 1st year

Population density

Annual average temperature

Controlling for confounders, countries without BCG policy have increased COVID-19 associated mortality compared to those with BCG policy

Brooks et al. (2021) [34]

Linear regression

GDP

Population density

Total population

Population over 65

Average temperature

Stringency index

Polio and measles vaccine coverage

BCG vaccination was consistently associated with lower COVID-19 related mortality

Abdulah and Hassan (2021) [35]

Generalized linear model

Health system indicators

Social insurance

Social assistance

Mandatory individual account system

Economic status based on the World Bank

MCV, DTP3, PCV vaccination

No significant association between infection and mortality and BCG vaccination

Rivas et al. (2021) [36]

Logistic regression

Pre-existing comorbidities

Age and sex

Pneumococcal, meningococcal, influenza vaccination

Decreased incidence of medically diagnosed or RT-PCR positive COVID-19 in those with history of BCG vaccination

Controlling for age, sex and comorbidities, less seroconversion and significantly lower anti-SARS-CoV-2 IgG index were seen in those with history of BCG vaccination

Klinger et al. (2020) [37]

Linear regression

Quarantine status

Economic development indicators

Chronic disease prevalence

Death rate from cardiovascular disorders

BCG administration years is consistently within the top two most significant coefficients compared to 23 confounding variables and ranks high in terms of coefficient effect