Possible Correlation between Bacillus Calmette Guérin (BCG) Vaccination Policy and SARS-Cov-2 Transmission, Morbidity and Mortality Rates: Implications for the African Continent

ABSTRACTThe Bacillus Calmette-Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is proposed to provide protection to non-TB infectious diseases. The COVID-19 outbreak results from infection with the novel coronavirus SARS-CoV-2 (CoV-2) and was declared a pandemic on March 11th, 2020. We queried whether the BCG vaccine offers protection against CoV-2 infection. We observed that countries with a current universal BCG vaccination policy have a significantly lower COVID-19 incidence than countries which never had a universal BCG policy or had one in the past. However, population density, median age, TB incidence, urban population, and, most significantly, CoV-2 testing rate, were also connected with BCG policy and could potentially confound the analysis. By limiting the analysis to countries with high CoV-2 testing rates, defined as greater than 2,500 tests per million inhabitants, these parameters were no longer statistically associated with BCG policy. When analyzing only countries with high testing rates, there was no longer a significant association between the number of COVID-19 cases per million inhabitants and the BCG vaccination policy. Although preliminary, our analyses indicate that the BCG vaccination may not offer protection against CoV-2 infection. While reporting biases may confound our observations, our findings support exercising caution in determining potential correlation between BCG vaccination and COVID-19 incidence, in part due significantly lower rates of CoV-2 testing per million inhabitants in countries with current universal BCG vaccination policy.

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Relationship between Bacillus Calmette Guerin Vaccination Policy and Coronavirus Disease-2019 (COVID-19) Incidence

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v20i1.5417 ◽

2021 ◽

Author(s):

Soheila Alyasin ◽

Zahra Kanannejad ◽

Hossein Esmaeilzadeh ◽

Hesamedin Nabavizadeh ◽

Mohammad Amin Ghatee ◽

...

Keyword(s):

Clinical Trial ◽

Large Scale ◽

Mortality Rates ◽

Epidemiological Studies ◽

Bcg Vaccine ◽

Confounding Factors ◽

Protective Effects ◽

Bacillus Calmette Guerin ◽

Vaccination Policy ◽

Bcg Vaccination

Bacillus Calmette Guerin (BCG) was designed for protecting children against tuberculosis. Also, it can protect against other infectious diseases through the induction of trained immunity. Due to its heterologous protective effects, the BCG vaccine has been proposed as a treatment option for coronavirus disease-2019 (COVID-19). Epidemiological studies have found that countries without BCG vaccination policy have experienced higher mortality rates related to COVID-19 infection than those with BCG vaccination policy. However, there are some confounding factors such as age, population intensity, immigration, the pandemic phase, and data accuracy that may affect these results. Therefore, this hypothesis should be evaluated by clinical trial studies. Large-scale clinical trials are in progress to investigate if the BCG vaccine could be used as a useful tool for protection against COVID-19 infection.

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Correlation between immunity from BCG and the morbidity and mortality of COVID-19

10.21203/rs.3.rs-29399/v3 ◽

2020 ◽

Author(s):

Dakshitha Wickramasinghe ◽

Nilanka Wickramasinghe ◽

Sohan Anjana Kamburugamuwa ◽

Carukshi Arambepola ◽

Dharmabandhu N Samarasekera

Keyword(s):

Linear Regression Analysis ◽

Univariate Analysis ◽

Case Fatality ◽

Income Level ◽

Morbidity And Mortality ◽

Vaccination Policy ◽

Specific Data ◽

Bcg Vaccination ◽

Country Level ◽

Country Specific

Abstract Background To investigate the association between parameters indicating immunity from BCG at country level (presence of BCG vaccination policy, BCG coverage, age-specific incidence of tuberculosis(TB)) and the morbidity and mortality of COVID-19. Methods Country-specific data for COVID-19 cases and deaths, demographic details, BCG coverage and policy, age-specific TB incidence and income level were obtained. The crude COVID-19 cases and deaths per 100,000 population were calculated and assessed against the parameters indicating immunity from BCG using linear regression analysis. Results Univariate analysis identified higher income level of a country to be significantly associated with COVID-19 cases (p<0.0001) and deaths (p<0.0001) but not with its case fatality rate. The association between COVID-19 and TB was strongest for TB incidence in patients >65-years (Cases(rs=-0.785,p=0.0001)) and deaths (rs=-0.647,p=0.0001).Multivariate analysis identified the higher income level of a country and not having a universal BCG vaccination policy to affect the COVID-19 cases. The deaths were inversely affected by the presence of BCG vaccination policy and coverage; and positively by the TB incidence in patients >65-years. Conclusion Significant inverse correlations observed between cases and deaths of COVID-19 and BCG related parameters highlights immunity from BCG as a likely explanation for the variation in COVID-19 across countries.

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Correlation between immunity from BCG and the morbidity and mortality of COVID-19

10.21203/rs.3.rs-29399/v1 ◽

2020 ◽

Author(s):

Dakshitha Wickramasinghe ◽

Nilanka Wickramasinghe ◽

Sohan Anjana Kamburugamuwa ◽

Carukshi Arambepola ◽

Dharmabandhu N Samarasekera

Keyword(s):

Linear Regression Analysis ◽

Univariate Analysis ◽

Case Fatality ◽

Income Level ◽

Morbidity And Mortality ◽

Vaccination Policy ◽

Specific Data ◽

Bcg Vaccination ◽

Country Level ◽

Country Specific

Abstract Purpose To investigate the association between parameters indicating immunity from BCG at country level (presence of BCG vaccination policy, BCG coverage, age-specific incidence of tuberculosis (TB)) and the morbidity and mortality of COVID-19. Methods Country-specific data for COVID-19 cases and deaths, demographic details, BCG coverage and policy, age-specific TB incidence and income level were obtained. The crude COVID-19 cases and deaths per 100,000 population were calculated and assessed against the parameters indicating the immunity from BCG using linear regression analysis. Results Univariate analysis identified higher income level of a country to be significantly associated with COVID-19 cases (p<0.0001) and deaths (p<0.0001) but not with its case fatality rate. The association between COVID-19 and TB was strongest for TB incidence in patients >65-years (Cases(r s =-0.785,p=0.0001)) and deaths (r s =-0.647,p=0.0001). Multivariate analysis identified the higher income level of a country and not having a universal BCG vaccination policy to affect the COVID-19 cases. The deaths were affected negatively by the presence of BCG vaccination policy and coverage; and positively by the TB incidence in patients >65-years. Conclusion Significant negative correlations observed between cases and deaths of COVID-19 and parameters indicating immunity from BCG highlight a likely explanation for the variation in COVID-19 across countries.

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Does TB Vaccination Reduce COVID-19 Infection?: No Evidence from a Regression Discontinuity and Difference-in-Differences Analysis

10.21203/rs.3.rs-56123/v1 ◽

2020 ◽

Author(s):

Hiroaki Matsuura ◽

Masao Fukui ◽

Kohei Kawaguchi

Keyword(s):

Scientific Community ◽

Regression Discontinuity ◽

Universal Coverage ◽

Regression Discontinuity Design ◽

Bacillus Calmette Guerin ◽

Vaccination Policy ◽

Difference In Differences ◽

Bcg Vaccination ◽

Cross Country

Abstract In the middle of the global COVID-19 pandemic, the BCG hypothesis, the prevalence and severity of the COVID-19 outbreak seems to be negatively correlated with whether a country has a universal coverage of pediatric Bacillus Calmette–Guérin (BCG) vaccination, has emerged and attracted the attention of scientiﬁc community and media outlets. However, all existing claims are based on cross-country correlations that do not exclude the possibility of spurious correlation. By merging country-age-level confirmed case statistics of COVID-19 from 17 countries with the start/termination years of pediatric universal BCG vaccination policy and age-specific BCG vaccination coverage, this paper examines the role of BCG vaccination in COVID-19 infection. Despite the cross-country evidence from the previous literature, the results of both regression discontinuity design and difference-in-differences approaches do not support the BCG hypothesis.The results of these previous studies are likely to suffer from spurious correlations.

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Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study

10.1101/2020.03.24.20042937 ◽

2020 ◽

Cited By ~ 156

Author(s):

Aaron Miller ◽

Mac Josh Reandelar ◽

Kimberly Fasciglione ◽

Violeta Roumenova ◽

Yan Li ◽

...

Keyword(s):

Elderly Population ◽

Respiratory Infections ◽

Morbidity And Mortality ◽

Childhood Vaccination ◽

Cultural Norms ◽

Vaccination Policy ◽

Bcg Vaccination ◽

National Differences ◽

Late Start ◽

The Impact

AbstractCOVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID- 19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guérin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.

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Association between COVID-19 morbidity and mortality rates and BCG vaccination policies in OECD countries

Journal of Infection Prevention ◽

10.1177/1757177420976812 ◽

2020 ◽

pp. 175717742097681

Author(s):

Yuki Senoo ◽

Yosuke Suzuki ◽

Kenji Tsuda ◽

Tetsuya Tanimoto ◽

Kenzo Takahashi

Keyword(s):

Protective Effect ◽

Mortality Rates ◽

Oecd Countries ◽

Morbidity And Mortality ◽

Bcg Vaccination

We compared whether the national BCG vaccination (BCGV) policy influenced coronavirus disease 2019 (COVID-19) in Organisation for Economic Co-operation and Development (OECD) countries. Those currently implementing BCGV have a reduced number of COVID-19 morbidity and mortality cases, compared to those who have never implemented a BCGV policy, suggesting the potential protective effect of BCGV against COVID-19.

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Correlation between immunity from BCG and the morbidity and mortality of COVID-19

10.21203/rs.3.rs-29399/v2 ◽

2020 ◽

Author(s):

Dakshitha Wickramasinghe ◽

Nilanka Wickramasinghe ◽

Sohan Anjana Kamburugamuwa ◽

Carukshi Arambepola ◽

Dharmabandhu N Samarasekera

Keyword(s):

Linear Regression Analysis ◽

Univariate Analysis ◽

Case Fatality ◽

Income Level ◽

Morbidity And Mortality ◽

Vaccination Policy ◽

Specific Data ◽

Bcg Vaccination ◽

Country Level ◽

Country Specific

Abstract Background To investigate the association between parameters indicating immunity from BCG at country level (presence of BCG vaccination policy, BCG coverage, age-specific incidence of tuberculosis(TB)) and the morbidity and mortality of COVID-19. Methods Country-specific data for COVID-19 cases and deaths, demographic details, BCG coverage and policy, age-specific TB incidence and income level were obtained. The crude COVID-19 cases and deaths per 100,000 population were calculated and assessed against the parameters indicating immunity from BCG using linear regression analysis. Results Univariate analysis identified higher income level of a country to be significantly associated with COVID-19 cases (p<0.0001) and deaths (p<0.0001) but not with its case fatality rate. The association between COVID-19 and TB was strongest for TB incidence in patients >65-years (Cases(rs=-0.785,p=0.0001)) and deaths (rs=-0.647,p=0.0001).Multivariate analysis identified the higher income level of a country and not having a universal BCG vaccination policy to affect the COVID-19 cases. The deaths were inversely affected by the presence of BCG vaccination policy and coverage; and positively by the TB incidence in patients >65-years. Conclusion Significant inverse correlations observed between cases and deaths of COVID-19 and BCG related parameters highlights immunity from BCG as a likely explanation for the variation in COVID-19 across countries.

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Statistical Analysis on the Impact of BCG Vaccination Policy of Different Economies on Coronavirus

International Journal for Research in Applied Science and Engineering Technology ◽

10.22214/ijraset.2021.36344 ◽

2021 ◽

Vol 9 (VII) ◽

pp. 3038-3046

Author(s):

Aniket Modi

Keyword(s):

Statistical Analysis ◽

Mortality Rate ◽

Mortality Rates ◽

Protective Effects ◽

The Novel ◽

Vaccination Policy ◽

Bcg Vaccination ◽

Novel Coronavirus ◽

National Programs ◽

The Impact

The novel coronavirus SARS-Cov-2 (Cov-2) results in COVID-19 infection which affects the respiratory tract of the human body, so we investigated whether the BCG vaccine offers some protection against CoV-2 infection. Herein we examine whether the national programs that use BCG vaccination to reduce tuberculosis infections might be responsible for different incident and mortality rates which is observed in Covid-19 among various countries. There is some mechanistic evidence that shows the BCG vaccination can have some protective effects against the Covid-19 virus. Through our observation, we see that countries that still follow BCG vaccination policy have a significantly lower mortality rate than those countries that have discontinued this policy or never had one.

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Association of BCG vaccination policy with prevalence and mortality of COVID-19

10.1101/2020.03.30.20048165 ◽

2020 ◽

Cited By ~ 25

Author(s):

Giovanni Sala ◽

Tsuyoshi Miyakawa

Keyword(s):

Large Scale ◽

Confounding Factor ◽

Epidemiological Studies ◽

Bacillus Calmette Guerin ◽

Vaccination Policy ◽

Bcg Vaccination ◽

Beneficial Effects ◽

Average Temperature ◽

Significant Difference ◽

Linear Regression Modeling

AbstractThere is some evidence that tuberculosis vaccine bacillus Calmette-Guérin (BCG) has non-specific beneficial effects against non-related infections. Here, we examined the possible association between BCG vaccination with prevalence and mortality by COVID-19 by using publicly available data of COVID-19 in 199 countries/regions and the BCG World Atlas. By using linear regression modeling, we found that the number of total cases and deaths per one million population were significantly associated with the country’s policy concerning BCG vaccine administration. The amount of variance in cases and deaths explained by BCG vaccination policy ranged between 12.5% and 38%. Importantly, this effect remained significant after controlling for the country’s life expectancy and the average temperature in February and March 2020, which themselves are significantly correlated with the cases and deaths indices, respectively. By contrast, the ratio between deaths and cases was weakly affected. This latter outcome suggested that BCG vaccination may have hindered the overall spread of the virus or progression of the disease rather than reducing mortality rates (i.e., deaths/cases ratio). Finally, by roughly dividing countries into three categories showing high, middle, or low growth rate of the cases, we found a highly significant difference between the slope categories among the BCG groups, suggesting that the time since the onset of the spread of the virus was not a major confounding factor. While this retrospective epidemiological study potentially suffers from a number of unknown confounding factors, these associations support the idea that BCG vaccination may provide protection against SARS-CoV-2, which, together with its proven safety, encourages consideration of further detailed epidemiological studies, large-scale clinical trials on the efficacy of this vaccine on COVID-19, and/or re-introduction of BCG vaccination practice in the countries which are currently devoid of the practice.

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