The Natural Effect of BCG Vaccination on COVID-19: The Debate Continues
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ABSTRACT:
SUBMITTER: Gong W
PROVIDER: S-EPMC9309283 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:While awaiting the COVID-19 vaccines, researchers have been actively exploring the effectiveness of existing vaccines against the new virus, among which the BCG vaccine (Bacillus Calmette-Guérin) receives the most attention. While many reports suggest a potential role for BCG immunization in ameliorating SARS-CoV-2 infection, these findings remain controversial. With country-level COVID-19 outbreak data from Johns Hopkins University Coronavirus Resource Center, and BCG program data from World Atlas of BCG Policies and Practices and WHO/UNICE, we estimated a dynamic model to investigate the effect of BCG vaccination across time during the pandemic. Our results reconcile these varying reports regarding protection by BCG against COVID-19 in a variety of clinical scenarios and model specifications. We observe a notable protective effect of the BCG vaccine during the early stage of the pandemic. However, we do not see any strong evidence for protection during the later stages. We also see that a higher proportion of vaccinated young population may confer some level of communal protection against the virus in the early pandemic period, even when the proportion of vaccination in the older population is low. Our results highlight that while BCG may offer some protection against COVID-19, we should be cautious in interpreting the estimated effectiveness as it may vary over time and depend on the age structure of the vaccinated population.
| S-EPMC8052320 | biostudies-literature
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:There is significant public and clinical interest in the potential for Bacillus Calmette-Guérin (BCG) vaccination to protect against type 2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) induced COVID-19. This question could be best answered by blinded and placebo controlled clinical trials. However, a skin reaction occurs within days at the site of BCG injection, making it rather challenging to blind this vaccination. Here, we examined registered clinical trials in ClinicalTrials.gov on BCG against COVID-19 by October 9th 2020, and found that 94.7% of such trials were listed as placebo controlled (all with normal saline as placebo), and single to quadruple blinded. The mode of overcoming the natural unblinding by the BCG induced skin reaction was not clarified on the website in either of the trials. We conclude that detailed description of the strategy towards overcoming the BCG vaccination induced skin reaction associated unblinding hurdle will be important for the interpretation of the theoretically blinded COVID-19 directed clinical trials.
| S-EPMC7969911 | 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:Presentation of the Case A 37-year-old woman presented at 35 weeks of gestation with her third child with failure to adequately gain weight and was noted by her obstetrician to have delay in the growth of her baby. Ultrasound of the abdomen incidentally revealed the presence of a liver lesion. After additional evaluation, she ultimately delivered her daughter at 36 weeks uneventfully. She subsequently underwent additional evaluation. Liver magnetic resonance imaging (MRI) revealed a 5-cm solitary solid mass in segment 4A of the liver, concerning for malignancy. Serum α-fetoprotein, carcinoembryonic antigen, cancer antigen (CA)19-9, CA15-3, and CA125 were all normal. Liver biopsy was positive for adenocarcinoma. The tumor cells demonstrated a phenotype suggesting a possible breast primary, although the immunohistochemistry did not support that diagnosis and the tumor was negative for mammaglobin, gross cystic disease fluid protein (GCDFP)-15, estrogen receptor (ER), and progesterone receptor (PR) (Table 1). The tumor was also CDX2 and cardiotrophin-1 negative, but cytokeratin (CK) 19 positive. Her endoscopic retrograde cholangiopancreatography, upper endoscopy, colonoscopy, breast mammogram, and breast MRI were completely normal. A positron emission tomography-computed tomography scan showed a fluorodeoxyglucose-avid 5.8-cm × 6.0-cm hypoattenuating lesion with peripheral enhancement involving segment 4 and segment 8 at the dome. In addition, central necrosis within the lesion was noted. The left main portal vein was mildly attenuated by the mass. She eventually underwent a left hepatectomy en bloc with caudate resection, portal lymphadenectomy, cholecystectomy, and omental pedicle flap. On exploration of the abdomen, no additional disease was noted. The final pathology revealed a 9.4-cm moderately to poorly differentiated adenocarcinoma of the intrahepatic bile ducts. Venous invasion was present. Perineural invasion was absent. The margins were negative. Thirteen lymph nodes were obtained, all of which were negative, consistent with a stage T2, N0, MX intrahepatic cholangiocarcinoma. The tumor was positive for CK7, CK19, and CA19-9 and negative for CK20, CDX2, CA125, ER, PR, GCDFP-15, synaptophysin, and chromogranin (Table 1). The uninvolved liver was unremarkable and a trichrome stain showed no fibrosis. Following an uneventful postoperative recovery, she was referred for consideration of adjuvant therapy.
| S-EPMC3528382 | 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:Bacillus Calmette-Guérin (BCG) vaccine is currently used to prevent tuberculosis infection. The vaccine was found to enhance resistance to certain types of infection including positive sense RNA viruses. The current COVID-19 pandemic is caused by positive sense RNA, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A higher mortality rate of COVID-19 patients was reported in countries where BCG vaccination is not routinely administered, when compared to the vaccinated ones. We hypothesized that BCG vaccine may control SARS-CoV2 infection via modulating the monocyte immune response. We analyzed GSE104149 dataset to investigate whether human monocytes of BCG-vaccinated individuals acquire resistance to SARS-CoV-2 infection. Differentially expressed genes obtained from the dataset were used to determine enriched pathways, biological processes, and molecular functions for monocytes post BCG vaccination. Our data show that BCG vaccine promotes a more effective immune response of monocytes against SARS-CoV2, but probably not sufficient to prevent the infection.
| S-EPMC8552046 | 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