BCG vaccination and the risk of COVID 19: A possible correlation.
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ABSTRACT:
SUBMITTER: Ahmed SM
PROVIDER: S-EPMC8552046 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has kept the whole world in tenterhooks due to its severe life-threatening infectious disease, COVID-19. The virus is distinct from its cousins, SARS-CoV and MERS-CoV in terms of severity of the infection. The obligated killing properties of the SARS-CoV-2 virus is mediated by its unique structure. Efforts for developing vaccines for COVID-19 are ongoing, but it is unlikely to be available in the immediate future. Due to the absence of precise treatment, the investigators are discovering other effective, protective, and healing choices. However, the lower than a predictable number of SARS-CoV-2 cases in countries with fragile health systems is mystifying. Recently, there has been a buzz about the protective effect of Bacille Calmette-Guérin (BCG) vaccine in COVID-19 through long-term boosting of trained immunity. Based on epidemiological correlations, we link up that BCG vaccination adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated mortality through the vaccine's capacity to confer heterologous protection. A number of clinical studies are underway to investigate this possibility but even if they prove effective-many questions will remain. Moreover, responsible stewardship of the BCG vaccine in the context of the COVID-19 epidemic is directly needed.
| S-EPMC7461084 | biostudies-literature
Project description:Current results do not provide conclusive evidence on the effect of BCG vaccination on COVID-19 alone or in combination with other factors. To address this limitation, in this study we used a citizen science initiative on the COVID-19 pandemic to collect data worldwide during 2 October 2020-30 October 2020 (1,233 individuals) in a structured way for analysing factors and characteristics of affected individuals in relation to BCG vaccination. For the first time, the results of our study suggested that vaccination with BCG may increase the risk for COVID-19 at certain age, particularly in individuals vaccinated at childhood. Childhood BCG vaccination increased the likelihood of being diagnosed with COVID-19 fivefold in COVID-19 low-incidence countries and threefold in high-incidence countries. A reasonable explanation for this effect is the activation of certain innate immunity mechanisms associated with inflammatory reactions. These factors should be considered when analysing the risks associated with this global pandemic.
| S-EPMC8251061 | biostudies-literature
Project description:The ongoing severe acute respiratory sickness coronavirus 2 (SARS-CoV-2) pandemic has resulted in more than 3,600,000 detected cases of COVID-19 illness and nearly 260,000 deaths worldwide as of May 6, 2020. Recently, BCG vaccination was shown to correlate with reduced COVID-19 case fatality rates (preprint: Miller et al, 2020; preprint: Sala & Miyakawa, 2020; https://www.jsatonotes.com/2020/03/if-i-were-north-americaneuropeanaustral.html). The most recent data from publicly available resources also indicate that both COVID-19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs. As seen in Table 1, seven of eight countries with very low numbers of total deaths (< 40 per 1 million population) adopted a mandatory BCG vaccination program using one of a set of 6 separate BCG strains (Table 1). In contrast, COVID-19 mortality was markedly higher in countries where BCG vaccination is not widely administered or is given only to high-risk groups. COVID-19 mortality was also higher in countries where widespread BCG vaccination was discontinued more than 20 years ago and in countries that used the BCG Denmark strain regularly or temporarily. This raises the question of whether BCG vaccination and reduced COVID-19 mortality are causally related. An additional question is why different BCG strains may be variably associated with mortality.
| S-EPMC7267326 | biostudies-literature
Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), and its variants have brought unprecedented impacts to the global public health system, politics, economy, and other fields. Although more than ten COVID-19 specific vaccines have been approved for emergency use, COVID-19 prevention and control still face many challenges. Bacille Calmette-Guérin (BCG) is the only authorized vaccine used to fight against tuberculosis (TB), it has been hypothesized that BCG may prevent and control COVID-19 based on BCG-induced nonspecific immune responses. Herein, we summarized: 1) The nonspecific protection effects of BCG, such as prophylactic protection effects of BCG on nonmycobacterial infections, immunotherapy effects of BCG vaccine, and enhancement effect of BCG vaccine on unrelated vaccines; 2) Recent evidence of BCG's efficacy against SARS-COV-2 infection from ecological studies, analytical analyses, clinical trials, and animal studies; 3) Three possible mechanisms of BCG vaccine and their effects on COVID-19 control including heterologous immunity, trained immunity, and anti-inflammatory effect. We hope that this review will encourage more scientists to investigate further BCG induced non-specific immune responses and explore their mechanisms, which could be a potential tool for addressing the COVID-19 pandemic and COVID-19-like "Black Swan" events to reduce the impacts of infectious disease outbreaks on public health, politics, and economy.
| S-EPMC9113676 | biostudies-literature
Project description:ObjectivesThe incidence of emerging coronavirus disease 2019 (COVID-19) disease is variable across the different parts of the world. Apart from travel patterns, other factors determining this difference may include host immune response. The aim of this study was to assess the effect of tuberculosis (TB) endemicity and Bacille Calmette-Guerin (BCG) coverage on COVID-19.Study designThis was a cross-sectional study.MethodsWe reviewed available data regarding TB incidence, BCG coverage (as per the World Health Organization), and COVID-19 incidence of 174 countries. We divided the countries into four cohorts depending on annual TB incidence and BCG coverage.ResultsCountries with high TB incidence had lower COVID-19 than countries with low TB incidence. Similarly, countries with high BCG coverage had lower incidence of COVID-19, suggesting some protective mechanisms in TB-endemic areas. However, the ecological differences and different testing strategies between countries could not be accounted for in this analysis.ConclusionHigher TB incidence and BCG coverage were found to be associated with lesser incidence of COVID-19. This outcome paves the way for further research into pathogenesis and immune response in COVID-19.
| S-EPMC7260483 | biostudies-literature
Project description:BackgroundSeveral ecologic studies have suggested that the bacillus Calmette-Guérin (BCG) vaccine may be protective against SARS-CoV-2 infection including a highly-cited published pre-print by Miller et al., finding that middle/high- and high-income countries that never had a universal BCG policy experienced higher COVID-19 burden compared to countries that currently have universal BCG vaccination policies. We provide a case study of the limitations of ecologic analyses by evaluating whether these early ecologic findings persisted as the pandemic progressed.MethodsSimilar to Miller et al., we employed Wilcoxon Rank Sum Tests to compare population medians in COVID-19 mortality, incidence, and mortality-to-incidence ratio between countries with universal BCG policies compared to those that never had such policies. We then computed Pearson's r correlations to evaluate the association between year of BCG vaccination policy implementation and COVID-19 outcomes. We repeated these analyses for every month in 2020 subsequent to Miller et al.'s March 2020 analysis.ResultsWe found that the differences in COVID-19 burden associated with BCG vaccination policies in March 2020 generally diminished in magnitude and usually lost statistical significance as the pandemic progressed. While six of nine analyses were statistically significant in March, only two were significant by the end of 2020.DiscussionThese results underscore the need for caution in interpreting ecologic studies, given their inherent methodological limitations, which can be magnified in the context of a rapidly evolving pandemic in which there is measurement error of both exposure and outcome status.
| S-EPMC9488757 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) is caused by the infection of highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as the novel coronavirus. In most countries, the containment of this virus spread is not controlled, which is driving the pandemic towards a more difficult phase. In this study, we investigated the impact of the Bacille Calmette Guerin (BCG) vaccination on the severity and mortality of COVID-19 by performing transcriptomic analyses of SARS-CoV-2 infected and BCG vaccinated samples in peripheral blood mononuclear cells (PBMC). A set of common differentially expressed genes (DEGs) were identified and seeded into their functional enrichment analyses via Gene Ontology (GO)-based functional terms and pre-annotated molecular pathways databases, and their Protein-Protein Interaction (PPI) network analysis. We further analysed the regulatory elements, possible comorbidities and putative drug candidates for COVID-19 patients who have not been BCG-vaccinated. Differential expression analyses of both BCG-vaccinated and COVID-19 infected samples identified 62 shared DEGs indicating their discordant expression pattern in their respected conditions compared to control. Next, PPI analysis of those DEGs revealed 10 hub genes, namely ITGB2, CXCL8, CXCL1, CCR2, IFNG, CCL4, PTGS2, ADORA3, TLR5 and CD33. Functional enrichment analyses found significantly enriched pathways/GO terms including cytokine activities, lysosome, IL-17 signalling pathway, TNF-signalling pathways. Moreover, a set of identified TFs, miRNAs and potential drug molecules were further investigated to assess their biological involvements in COVID-19 and their therapeutic possibilities. Findings showed significant genetic interactions between BCG vaccination and SARS-CoV-2 infection, suggesting an interesting prospect of the BCG vaccine in relation to the COVID-19 pandemic. We hope it may potentially trigger further research on this critical phenomenon to combat COVID-19 spread.
| S-EPMC8479467 | biostudies-literature
Project description:In a recent study of our group with the acronym ACTIVATE, Bacillus Calmete-Guérin (BCG) vaccination reduced the occurrence of new infections compared to placebo vaccination in the elderly. Most benefit was found for respiratory infections. The ACTIVATE-2 study was launched to assess the efficacy of BCG vaccination against coronavirus disease 2019 (COVID-19). In this multicenter, double-blind trial, 301 volunteers aged 50 years or older were randomized (1:1) to be vaccinated with BCG or placebo. The trial end points were the incidence of COVID-19 and the presence of anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies, which were both evaluated through 6 months after study intervention. Results revealed 68% relative reduction of the risk to develop COVID-19, using clinical criteria or/and laboratory diagnosis, in the group of BCG vaccine recipients compared with placebo-vaccinated controls, during a 6-month follow-up (OR 0.32, 95% CI 0.13-0.79). In total, eight patients were in need of hospitalization for COVID-19: six in the placebo group and two in the BCG group. Three months after study intervention, positive anti-SARS-CoV-2 antibodies were noted in 1.3% of volunteers in the placebo group and in 4.7% of participants in BCG-vaccinated group. These data indicate that BCG vaccination confers some protection against possible COVID-19 among patients older than 50 years with comorbidities. BCG vaccination may be a promising approach against the COVID-19 pandemic.
| S-EPMC9294453 | biostudies-literature
Project description:Data have not been reported to explore the relation between COVID-19 severity and BCG vaccination status at the individual patient level. Taiwan has a nationwide neonatal BCG vaccination program that was launched in 1965. The Taiwan Centers for Disease Control established a web-based National Immunization Information System (NISS) in 2003 and included all citizens' BCG vaccination records in NISS for those born after 1985. We identified COVID-19 Taiwanese patients born after 1985 between 21 January and 19 March 2021. Study participants were further classified into ages 4-24 years (birth year 1996-2016) and 25-33 years (birth year 1986-1995). We described their clinical syndrome defined by the World Health Organization and examined the relation between the COVID-19 severity and BCG vaccination status. In the 4-24 age group, among 138 BCG vaccinated individuals, 80.4% were asymptomatic or had mild disease, while 17.4% had moderate disease, 1.5% had severe disease, and 0.7% had acute respiratory distress syndrome but none of them died. In contrast, all 6 BCG unvaccinated individuals in this age group experienced mild illness. In the 25-33 age group, moderate disease occurred in 14.2% and severe disease occurred in 0.9% of the 106 patients without neonatal BCG vaccination records, as compared to 19.2% had moderate disease and none had severe or critical disease of the 78 patients with neonatal BCG vaccination records. Our finding indicated that BCG immunization might not relate to COVID-19 severity in the young population.
| S-EPMC8074147 | biostudies-literature
Project description:The Bacillus Calmette-Guérin (BCG) is a well-known vaccine with almost a century of use, with the apparent capability to improve cytokine production and epigenetics changes that could develop a better response to pathogens. It has been postulated that BCG protection against SARS-CoV-2 has a potential role in the pandemic, through the presence of homologous amino acid sequences. To identify a possible link between BCG vaccination coverage and COVID-19 cases, we used official epidemic data and Ecuadorian Ministry of Health and Pan American Health Organization vaccination information. BCG information before 1979 was available only at a national level. Therefore, projections based on the last 20 years were performed, to compare by specific geographic units. We used a Mann-Kendall test to identify BCG coverage variations, and mapping was conducted with a free geographic information system (QGIS). Nine provinces where BCG vaccine coverage was lower than 74.25% show a significant statistical association (χ2 Pearson's = 4.800, df = 1, p = 0.028), with a higher prevalence of cases for people aged 50 to 64 years than in younger people aged 20 to 49 years. Despite the availability of BCG vaccination data and the mathematical models needed to compare these data with COVID-19 cases, our results show that, in geographic areas where BCG coverage was low, 50% presented a high prevalence of COVID-19 cases that were young; thus, low-coverage years were more affected.
| S-EPMC7912416 | biostudies-literature