Impact of Bacillus Calmette-Guerin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 infection.
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ABSTRACT:
SUBMITTER: COVID Surg Collaborative
PROVIDER: S-EPMC8756090 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe Bacillus Calmette-Guerin (BCG) vaccine has been in use for 99 years, and is regarded as one of the oldest human vaccines known today. It is recommended primarily due to its effect in preventing the most severe forms of tuberculosis, including disseminated tuberculosis and meningeal tuberculosis in children; however, its efficacy in preventing pulmonary tuberculosis and TB reactivation in adults has been questioned. Several studies however have found that asides from its role in tuberculosis prevention, the BCG vaccine also has protective effects against a host of other viral infections in humans, an effect which has been termed: heterologous, non-specific or off-target.ObjectivesAs we approach 100 years since the discovery of the BCG vaccine, we review the evidence of the non-specific protection offered by the vaccine against viral infections, discuss the possible mechanisms of action of these effects, highlight the implications these effects could have on vaccinology and summarize the recent epidemiological correlation between the vaccine and the on-going COVID-19 pandemic.ResultsSeveral epidemiological studies have established that BCG does reduce all-cause mortality in infants, and also the time of vaccination influences this effect significantly. This effect has been attributed to the protective effect of the vaccine in preventing unrelated viral infections during the neonatal period. Some of such viral infections that have been investigated include: herpes simplex virus (HSV), human Papilloma virus (HPV), yellow fever virus (YFV), respiratory syncytial virus (RSV) and influenza virus type A (H1N1). These effects are thought to be mediated via induction of innate immune memory as well as heterologous lymphocytic activation. While epidemiological studies have suggested a correlation, the potential protection of the BCG vaccine against COVID-19 transmission and mortality rates is currently unclear. Ongoing clinical trials and further research may shed more light on the subject in the future.ConclusionBCG is a multifaceted vaccine, with many numerous potential applications to vaccination strategies being employed for current and future viral infections. There however is a need for further studies into the immunologic mechanisms behind these non-specific effects, for these potentials to become reality, as we usher in the beginning of the second century since the vaccine's discovery.
| S-EPMC7921379 | biostudies-literature
Project description:Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis from livestock, particularly cattle. In Michigan, USA tuberculous white-tailed deer transmit M. bovis to other deer and cattle. One approach in dealing with this wildlife reservoir is to vaccinate deer, thus interfering with the intraspecies and interspecies transmission cycles. Thirty-three white-tailed deer were assigned to one of two groups; oral vaccination with 1 × 10(8) colony-forming units of M. bovis BCG Danish (n = 17); and non-vaccinated (n = 16). One hundred eleven days after vaccination deer were infected intratonsilarly with 300 colony-forming units of virulent M. bovis. At examination, 150 days after challenge, BCG vaccinated deer had fewer gross and microscopic lesions, fewer tissues from which M. bovis could be isolated, and fewer late stage granulomas with extensive liquefactive necrosis. Fewer lesions, especially those of a highly necrotic nature should decrease the potential for dissemination of M. bovis within the host and transmission to other susceptible hosts.
| S-EPMC4013142 | biostudies-other
Project description:As the SARS-CoV2 pandemic has progressed, there have been marked geographical differences in the pace and extent of its spread. We evaluated the association of BCG vaccination on morbidity and mortality of SARS-CoV2, adjusted for country-specific responses to the epidemic, demographics and health. SARS-CoV2 cases and deaths as reported by 31 May 2020 in the World Health Organization situation reports were used. Countries with at least 28 days following the first 100 cases, and available information on BCG were included. We used log-linear regression models to explore associations of cases and deaths with the BCG vaccination policy in each country, adjusted for population size, gross domestic product, proportion aged over 65 years, stringency level measures, testing levels, smoking proportion, and the time difference from date of reporting the 100th case to 31 May 2020. We further looked at the association that might have been found if the analyses were done at earlier time points. The study included 97 countries with 73 having a policy of current BCG vaccination, 13 having previously had BCG vaccination, and 11 having never had BCG vaccination. In a log-linear regression model there was no effect of country-level BCG status on SARS-CoV2 cases or deaths. Univariable log-linear regression models showed a trend towards a weakening of the association over time. We found no statistical evidence for an association between BCG vaccination policy and either SARS-CoV2 morbidity or mortality. We urge countries to rather consider alternative tools with evidence supporting their effectiveness for controlling SARS-CoV2 morbidity and mortality.
| S-EPMC7746266 | biostudies-literature
Project description:Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of a range of infectious diseases, and if so, it could protect against coronavirus disease 2019 (COVID-19). Here, we compared countries that mandated BCG vaccination until at least 2000 with countries that did not. To minimize any systematic effects of reporting biases, we analyzed the rate of the day-by-day increase in both confirmed cases (134 countries) and deaths (135 countries) in the first 30-day period of country-wise outbreaks. The 30-day window was adjusted to begin at the country-wise onset of the pandemic. Linear mixed models revealed a significant effect of mandated BCG policies on the growth rate of both cases and deaths after controlling for median age, gross domestic product per capita, population density, population size, net migration rate, and various cultural dimensions (e.g., individualism). Our analysis suggests that mandated BCG vaccination can be effective in the fight against COVID-19.
| S-EPMC7457335 | biostudies-literature
Project description:Primary immunodeficiency diseases (PIDs) are a group of inherited disorders, characterized by defects of the immune system predisposing individuals to variety of manifestations, including recurrent infections and unusual vaccine complications. There are a number of PIDs prone to Bacillus Calmette-Guérin (BCG) complications. This review presents an update on our understanding about the BCGosis-susceptible PIDs, including severe combined immunodeficiency, chronic granulomatous disease, and Mendelian susceptibility to mycobacterial diseases.
| S-EPMC4792288 | biostudies-literature
Project description:Physicians treating patients affected by nonmuscle-invasive bladder cancer (NMIBC) have been in shock during the last six years since manufacturing restrictions on the production of the first-option medicine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), have resulted in worldwide shortages. This shortage of BCG has led to a rethinking of the established treatment guidelines for the rationing of the administration of BCG. Some possible schedule modifications consist of a decrease in the length of maintenance treatment, a reduction in the dose of BCG in intravesical instillations or the use of different BCG substrains. All these strategies have been considered valuable in times of BCG shortage. In addition, the lack of availability of BCG has also led to the general recognition of the need to find new treatment options for these patients so that they are not dependent on a single treatment. Few alternatives are committed to definitively replacing BCG intravesical instillations, but several options are being evaluated to improve its efficacy or to combine it with other chemotherapeutic or immunotherapeutic options that can also improve its effect. In this article, we review the current state of the treatment with BCG in terms of all of the aforementioned aspects.
| S-EPMC7025668 | biostudies-literature
Project description:The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial off-target effects of BCG are proposed to be stronger amongst children who develop a BCG scar. Within an international randomised trial ('BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers'; BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination . Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2-0.9), BCG revaccination (OR 1.7, 95%CI 1.3-2.0), female sex (OR 2.0, 95%CI 1.7-2.4), older age (OR 0.4, 95%CI 0.4-0.5) and study country (Brazil OR 1.6, 95%CI 1.3-2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (96%) did not regret having the vaccine. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.
| S-EPMC10126857 | biostudies-literature
Project description:Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be a leading cause of mortality among bacterial diseases, and the bacillus Calmette-Guérin (BCG) is the only licensed vaccine for human use against this disease. TB prevention and control would benefit from an improved method of BCG vaccination that simplifies logistics and eliminates dangers posed by hypodermic needles without compromising immunogenicity. Here, we report the design and engineering of a BCG-coated microneedle vaccine patch for a simple and improved intradermal delivery of the vaccine. The microneedle vaccine patch induced a robust cell-mediated immune response in both the lungs and the spleen of guinea pigs. The response was comparable to the traditional hypodermic needle based intradermal BCG vaccination and was characterized by a strong antigen specific lymphocyte proliferation and IFN-? levels with high frequencies of CD4(+)IFN-?(+), CD4(+)TNF-?(+) and CD4(+)IFN-?(+)TNF-?(+) T cells. The BCG-coated microneedle vaccine patch was highly immunogenic in guinea pigs and supports further exploration of this new technology as a simpler, safer, and compliant vaccination that could facilitate increased coverage, especially in developing countries that lack adequate healthcare infrastructure.
| S-EPMC3127204 | biostudies-literature
Project description:BackgroundIntravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for bladder superficial carcinoma and it is being tested in interstitial cystitis patients, but its precise mechanism of action remains poorly understood. It is not clear whether BCG induces the release of a unique set of cytokines apart from its pro-inflammatory effects. Therefore, we quantified bladder inflammatory responses and alterations in urinary cytokine protein induced by intravesical BCG and compared the results to non-specific pro-inflammatory stimuli (LPS and TNF-alpha). We went further to determine whether BCG treatment alters cytokine gene expression in the urinary bladder.MethodsC57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-alpha. Morphometric analyses were conducted in bladders isolated from all groups and urine was collected for multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation combined with real-time polymerase chain reaction assay (CHIP/Q-PCR) was used to test whether intravesical BCG would alter bladder cytokine gene expression.ResultsAcute BCG instillation induced edema which was progressively replaced by an inflammatory infiltrate, composed primarily of neutrophils, in response to weekly administrations. Our morphological analysis suggests that these polymorphonuclear neutrophils are of prime importance for the bladder responses to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-alpha treatment but the major difference observed was the unique granuloma formation in response to BCG. Among the cytokines measured, this study highlighted the importance of IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and Rantes as discriminators between generalized inflammation and BCG-specific inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL-17B, IL-17RA, and IL-17RB.ConclusionTo the best of our knowledge, the present work is the first to report that BCG induces an increase in the IL-17 family genes. In addition, BCG induces a unique type of persisting bladder inflammation different from TNF-alpha, LPS, and, most likely, other classical pro-inflammatory stimuli.
| S-EPMC1891101 | 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