COVID-19 Related Mortality: Is the BCG Vaccine Truly Effective?

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has become a worldwide emergency. In the attempt to search for interventions that would improve outcomes, some studies have looked at the potential benefit of BCG vaccination. These past studies have found a statistically significant reduction in COVID-19 related mortality in countries with a current universal bacille Calmette-Guérin (BCG) vaccination policy. However, just as the authors themselves noted, the nature of ecological studies make them very prone to the presence of several confounders. This paper took into account demographic differences, economic differences and the different stages of the pandemic in each country; gathering data from publicly available sources. It was found that no statistically significant difference exists in mortality rates between countries with a current or prior BCG vaccination policy when compared to those that never had such a program. Nevertheless, the immunostimulatory potential of the BCG vaccine might still prove useful in the development of future vaccines or other prophylactic measures.

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Association of national Bacille Calmette-Guérin vaccination policy with COVID-19 epidemiology: an ecological study in 78 countries

10.1101/2020.05.13.20100156 ◽

2020 ◽

Author(s):

Norifumi Kuratani

Keyword(s):

Protective Mechanism ◽

Vaccination Policy ◽

Bacille Calmette Guerin ◽

Mixed Effect ◽

Bcg Vaccination ◽

Risk Of Death ◽

Effect Model ◽

Increase Rate ◽

A Current ◽

Country Specific

A possible association between national Bacille Calmette-Guérin (BCG) vaccination policy and lower COVID-19 incidence has been suggested in some preprint papers. Using publicly accessible databases, I explored associations of national BCG vaccination policy with COVID-19 epidemiology in 78 countries. Data collection was conducted from April 25 to May 5, 2020. I compared countries that have a current universal BCG vaccination policy (BCG countries), with countries that currently lack such a policy (non-BCG countries). The mixed effect model revealed national BCG policy decreases in the country-specific risk of death by COVID-19, correspond to odds ratio of 0.446 (95% confidence intervals 0.323 - 0.614, P =1×10-5). In BCG countries, the case increase rate was attenuated marginally by 25.4% (95% CI 3.0 to 42.7, P=0.029) as compared with those of the non-BCG countries. Although the protective mechanism of BCG vaccination against COVID-19 remains unknown, further laboratory and clinical research should be warranted.

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Exercising caution in correlating COVID-19 incidence and mortality rates with BCG vaccination policies due to variable rates of SARS CoV-2 testing

10.1101/2020.04.08.20056051 ◽

2020 ◽

Cited By ~ 13

Author(s):

Janine Hensel ◽

Kathleen M. McAndrews ◽

Daniel J. McGrail ◽

Dara P. Dowlatshahi ◽

Valerie S. LeBleu ◽

...

Keyword(s):

Mortality Rates ◽

Bcg Vaccine ◽

The Novel ◽

Bacillus Calmette Guerin ◽

Vaccination Policy ◽

Bcg Vaccination ◽

The Past ◽

Incidence And Mortality ◽

Novel Coronavirus ◽

A Current

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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Explore the Possible Impact of BCG Vaccination Policy on the Morbidity, Mortality, and Recovery Rates due to COVID-19 Infection. (Preprint)

10.2196/preprints.22052 ◽

2020 ◽

Author(s):

Yue-Cune Chang

Keyword(s):

Odds Ratio ◽

Randomized Clinical Trials ◽

Vaccination Policy ◽

Bacille Calmette Guerin ◽

Recovery Rates ◽

Bcg Vaccination ◽

The World ◽

New Form ◽

The Relationship ◽

Disease Specific

BACKGROUND The Coronavirus Disease-19 (COVID-19) is the new form of an acute infectious respiratory disease and has quickly spread over most continents in the world. Recently, it has been shown that Bacille Calmette-Guerin (BCG) might protect against COVID-19. This study aims to investigate the possible correlation between BCG vaccination and morbidity/mortality/recovery rate associated with COVID-19 infection. OBJECTIVE Our findings confirm that the BCG vaccination might protect against COVID-19 virus infection. METHODS Data of COVID-19 confirmed cases, deaths, recoveries, and population were obtained from https://www.worldometers.info/coronavirus/ (Accessed on 12 June, 2020). To have meaningful comparisons among countries’ mortality and recovery rates, we only choose those countries with COVID-19 infected cases at least 200. The Poisson regression and logistic regression were used to explore the relationship between BCG vaccination and morbidity, mortality and recovery rates. RESULTS Among those 158 countries with at least 200 COVID-19 infected cases, there were 141 countries with BCG vaccination information available. The adjusted rates ratio of COVID-19 confirmed cases for Current BCG vaccination vs. non-Current BCG vaccination was 0.339 (with 95% CI= (0.338,0.340)). Moreover, the adjusted odds ratio (OR) of death and recovery after coronavirus infected for Current BCG vaccination vs. non-Current BCG vaccination were 0.258 (with 95% CI= (0.254,0.261)) and 2.151 (with 95% CI= (2.140,2.163)), respectively. CONCLUSIONS That data in this study show the BCG might provide the protection against COVID-19, with consequent less COVID-19 infection and deaths and more rapid recovery. BCG vaccine might bridge the gap before the disease-specific vaccine is developed, but this hypothesis needs to be further tested in rigorous randomized clinical trials. INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1101/2020.06.14.20131268

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Effectiveness of the First Dose of BCG against Tuberculosis among HIV-Infected, Predominantly Immunodeficient Children

BioMed Research International ◽

10.1155/2015/275029 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Joaquim C. V. D. Van-Dunem ◽

Laura C. Rodrigues ◽

Luiz Claudio Arraes Alencar ◽

Maria de Fátima Pessoa Militão-Albuquerque ◽

Ricardo Arraes de Alencar Ximenes

Keyword(s):

Protective Effect ◽

Case Control Study ◽

Case Control ◽

Bcg Vaccine ◽

Bacille Calmette Guerin ◽

Bcg Vaccination ◽

Control Study

The objective of this study was to estimate the protective effect of Bacille Calmette-Guérin (BCG) vaccine against tuberculosis among (predominantly immunodeficient) HIV-infected children in Angola. A hospital-based case-control study was conducted with 230 cases, children coinfected with tuberculosis, and 672 controls, HIV-infected children from the same hospital, aged 18 months to 13 years. The presence of a vaccination scar was taken as a proxy marker for BCG vaccination. The crude effectiveness was 8% (95% CI: −26 to 32) and the adjusted effectiveness was 30% (95% CI: −75 to 72). The present study suggests that BCG does not have a protective effect against tuberculosis among immunodeficient HIV-infected children. Since BCG is no longer given to HIV-infected children, the study may not be replicated. Accepting that these findings should be considered with caution, they are nonetheless likely to be the last estimate of BCG efficacy in a sufficiently powered study.

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BCG Vaccination Program mitigates COVID19 Related Mortality: A Reality check

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210202142811 ◽

2021 ◽

Vol 22 ◽

Author(s):

Archana Pandita ◽

Audesh Bhat ◽

Anita Koul ◽

Shashank K Singh

Keyword(s):

Potential Role ◽

Respiratory Infections ◽

Cross Protection ◽

Childhood Vaccination ◽

Vaccination Program ◽

Vaccination Policy ◽

Bcg Vaccination ◽

Reality Check ◽

The World ◽

Related Mortality

: Since its origin in the Wuhan province of China in December 2019, Coronavirus disease 19 (COVID-19) has spread to most parts of the world and has infected millions of people. However, the significant variability in the mortality rate across the world indicates some underlying factors, especially the immunity factors that may have a potential role in this variability. One such factor that is being discussed and tested is the Bacillus Calmette-Guerin (BCG) vaccine. The available evidence suggests that BCG vaccination provides broad protection against respiratory infections as well as other infections. Therefore, BCG may prove to be a barrier for COVID-19 infection and may offer a ray of hope. In this review, we contrasted BCG vaccination program with COVID-19 mortality and analyzed trained immunity and cross protection against unrelated pathogens due to BCG vaccination. On analyzing the available data, we observed that countries without universal BCG vaccination policy are severely affected, while countries having universal BCG policies are less affected. Based on these data, we propose that the SARS-CoV-2 related qualified immunity, cross protection against unrelated pathogens and COVID-19 impact variations could be partly explained by the different national policies regarding BCG childhood vaccination. The combination of reduced morbidity and mortality may make BCG vaccination a potential new tool in the fight against COVID-19.

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Recent changes in tuberculosis control and BCG vaccination policy in France

Weekly releases (1997–2007) ◽

10.2807/esw.12.37.03268-en ◽

2007 ◽

Vol 12 (37) ◽

Cited By ~ 2

Author(s):

D Lévy-Bruhl ◽

M C Paty ◽

D Antoine ◽

D Bessette

Keyword(s):

Control Program ◽

Vaccination Policy ◽

Tuberculosis Control ◽

Bacille Calmette Guerin ◽

Bcg Vaccination ◽

National Tuberculosis Control Program ◽

Tuberculosis Control Program ◽

National Tuberculosis ◽

National Tuberculosis Control

On 11 July 2007, the French Minister of Health launched the National Tuberculosis Control Program and a new policy on Bacille Calmette-Guérin (BCG) vaccination.

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Vaccine-induced tuberculous osteomyelitis

10.32512/jmr.3.3.2020/20.21 ◽

2020 ◽

pp. 20-21

Keyword(s):

Injection Site ◽

Bcg Vaccine ◽

Bacille Calmette Guerin ◽

Bcg Vaccination ◽

Keywords Tuberculosis ◽

Tuberculous Osteomyelitis ◽

One Year ◽

Endemic Evolution

Tuberculosis (TB) has an endemic evolution in Tunisia. Bacille Calmette-Guerin (BCG) vaccination is systematically provided to all children. The vaccination is exceptionally complicated by a dissemination beyond the injection site (0.018 case per 100000 vaccination). We report a case of induced osteomyelitis in one-year old child following BCG vaccination. Keywords: Tuberculosis; BCG vaccine; Osteomyelitis; Management.

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COVID-19 pandemic: examining the faces of spatial differences in the morbidity and mortality in sub-Saharan Africa, Europe and USA

10.1101/2020.04.20.20072322 ◽

2020 ◽

Author(s):

Adebayo A. Otitoloju ◽

Ifeoma P. Okafor ◽

Mayowa Fasona ◽

Kafilat A. Bawa-Allah ◽

Chukwuemeka Isanbor ◽

...

Keyword(s):

Critical Evaluation ◽

Developed Countries ◽

Sub Saharan Africa ◽

Mean Annual Temperature ◽

Vaccination Policy ◽

African Countries ◽

Bcg Vaccination ◽

Malaria Burden ◽

Geographical Regions ◽

Significant Difference

AbstractBackgroundCOVID-19, the disease associated with the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is currently a global pandemic with several thousands of confirmed cases of infection and death. However, the death rate across affected countries shows variation deserving of critical evaluation.MethodsIn this study, we evaluated differentials in COVID-19 confirmed cases of infection and associated deaths of selected countries in Sub-Sahara Africa (Nigeria and Ghana), South Africa, Europe (Italy, Spain, Sweden and UK) and USA. Data acquired for various standard databases on mutational shift of the SARS-CoV-2 virus based on geographical location, BCG vaccination policy, malaria endemicity, climatic conditions (temperature), differential healthcare approaches were evaluated over a period of 45 days from the date of reporting the index case.ResultsThe number of confirmed cases of infection and associated deaths in Sub-Sahara Africa were found to be very low compared to the very high values in Europe and USA over the same period. Recovery rate from COVID-19 is not correlated with the mutational attributes of the virus with the sequenced strain from Nigeria having no significant difference (p>0.05) from other geographical regions. Significantly higher (p<0.05) infection rate and mortality from COVID-19 were observed in countries (Europe and USA) without a current universal BCG vaccination policy compared to those with one (Sub-Sahara African countries). Countries with high malaria burden had significantly lower (p<0.05) cases of COVID-19 than those with low malaria burden. A strong negative correlation (−0.595) between mean annual temperature and COVID-19 infection and death was observed with 14.8% variances between temperature and COVID-19 occurrence among the countries. A clear distinction was observed in the COVID-19 disease management between the developed countries (Europe and USA) and Sub-Sahara Africa.ConclusionsThe study established that the wide variation in the outcome of the COVID-19 disease burden in the selected countries are attributable largely to climatic condition (temperature) and differential healthcare approaches to management of the disease. We recommend consideration and mainstreaming of these findings for urgent intervention and management of COVID-19 across these continents.

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Gamma-Irradiated Bacille Calmette-Guérin Vaccination Does Not Modulate the Innate Immune Response during Experimental Human Endotoxemia in Adult Males

Journal of Immunology Research ◽

10.1155/2015/261864 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Linda A. C. Hamers ◽

Matthijs Kox ◽

Rob J. W. Arts ◽

Bastiaan Blok ◽

Jenneke Leentjens ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Ex Vivo ◽

Innate Immune ◽

Bcg Vaccine ◽

Controlled Study ◽

Bacille Calmette Guerin ◽

Bcg Vaccination ◽

Gamma Irradiated

Bacille Calmette-Guérin (BCG) vaccine exerts nonspecific immunostimulatory effects and may therefore represent a novel therapeutic option to treat sepsis-induced immunoparalysis. We investigated whether BCG vaccination modulates the systemic innate immune response in humansin vivoduring experimental endotoxemia. We used inactivated gamma-irradiated BCG vaccine because of the potential risk of disseminated disease with the live vaccine in immunoparalyzed patients. In a randomized double-blind placebo-controlled study, healthy male volunteers were vaccinated with gamma-irradiated BCG (n=10) or placebo (n=10) and received 1 ng/kg lipopolysaccharide (LPS) intravenously on day 5 after vaccination to assess thein vivoimmune response. Peripheral blood mononuclear cells were stimulated with various related and unrelated pathogens 5, 8 to 10, and 25 to 35 days after vaccination to assessex vivoimmune responses. BCG vaccination resulted in a scar in 90% of vaccinated subjects. LPS administration elicited a profound systemic immune response, characterized by increased levels of pro- and anti-inflammatory cytokines, hemodynamic changes, and flu-like symptoms. However, BCG modulated neither thisin vivoimmune response, norex vivoleukocyte responses at any time point. In conclusion, gamma-irradiated BCG is unlikely to represent an effective treatment option to restore immunocompetence in patients with sepsis-induced immunoparalysis. This trial is registered withNCT02085590.

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Explore the Possible Impact of BCG Vaccination Policy on the Morbidity, Mortality, and Recovery Rates due to COVID-19 Infection

10.1101/2020.06.14.20131268 ◽

2020 ◽

Author(s):

Chuan-Hsin Chang ◽

Yue-Cune Chang

Keyword(s):

Odds Ratio ◽

Randomized Clinical Trials ◽

Vaccination Policy ◽

Bacille Calmette Guerin ◽

Recovery Rates ◽

Bcg Vaccination ◽

The World ◽

New Form ◽

The Relationship ◽

Disease Specific

ABSTRACTBACKGROUNDThe Coronavirus Disease-19 (COVID-19) is the new form of an acute infectious respiratory disease and has quickly spread over most continents in the world. Recently, it has been shown that Bacille Calmette-Guerin (BCG) might protect against COVID-19. This study aims to investigate the possible correlation between BCG vaccination and morbidity/mortality/recovery rate associated with COVID-19 infection.METHODSData of COVID-19 confirmed cases, deaths, recoveries, and population were obtained from https://www.worldometers.info/coronavirus/ (Accessed on 12 June, 2020). To have meaningful comparisons among countries’ mortality and recovery rates, we only choose those countries with COVID-19 infected cases at least 200. The Poisson regression and logistic regression were used to explore the relationship between BCG vaccination and morbidity, mortality and recovery rates.RESULTSAmong those 158 countries with at least 200 COVID-19 infected cases, there were 141 countries with BCG vaccination information available. The adjusted rates ratio of COVID-19 confirmed cases for Current BCG vaccination vs. non-Current BCG vaccination was 0.339 (with 95% CI= (0.338,0.340)). Moreover, the adjusted odds ratio (OR) of death and recovery after coronavirus infected for Current BCG vaccination vs. non-Current BCG vaccination were 0.258 (with 95% CI= (0.254,0.261)) and 2.151 (with 95% CI= (2.140,2.163)), respectively.CONCLUSIONSThat data in this study show the BCG might provide the protection against COVID-19, with consequent less COVID-19 infection and deaths and more rapid recovery. BCG vaccine might bridge the gap before the disease-specific vaccine is developed, but this hypothesis needs to be further tested in rigorous randomized clinical trials.

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