Epidemiological transcriptomic data supports BCG protection in viral diseases including COVID-19.
Ontology highlight
ABSTRACT:
SUBMITTER: Sharma A
PROVIDER: S-EPMC7959679 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The COVID-19 pandemic, caused by type 2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), puts all of us to the test. Epidemiologic observations could critically aid the development of protective measures to combat this devastating viral outbreak. Recent observations, linked nation based universal Bacillus Calmette-Guerin (BCG) vaccination to potential protection against morbidity and mortality from SARS-CoV-2, and received much attention in public media. We wished to validate the findings by examining the country based association between COVID-19 mortality per million population, or daily rates of COVID-19 case fatality (i.e. Death Per Case/Days of the endemic [dpc/d]) and the presence of universal BCG vaccination before 1980, or the year of the establishment of universal BCG vaccination. These associations were examined in multiple regression modeling based on publicly available databases on both April 3rd and May 15th of 2020. COVID-19 deaths per million negatively associated with universal BCG vaccination in a country before 1980 based on May 15th data, but this was not true for COVID-19 dpc/d on either of days of inquiry. We also demonstrate possible arbitrary selection bias in such analyses. Consequently, caution should be exercised amidst the publication surge on COVID-19, due to political/economical-, arbitrary selection-, and fear/anxiety related biases, which may obscure scientific rigor. We argue that global COVID-19 epidemiologic data is unreliable and therefore should be critically scrutinized before using it as a nidus for subsequent hypothesis driven scientific discovery.
| S-EPMC7540851 | biostudies-literature
Project description:The Bacillus Calmette-Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is thought to provide protection against non-TB infectious diseases. BCG vaccination has recently been proposed as a strategy to prevent infection with SARS-CoV-2 (CoV-2) to combat the COVID-19 outbreak, supported by its potential to boost innate immunity and initial epidemiological analyses which observed reduced severity of COVID-19 in countries with universal BCG vaccination policies. Seventeen clinical trials are currently registered to inform on the benefits of BCG vaccinations upon exposure to CoV-2. Numerous epidemiological analyses showed a correlation between incidence of COVID-19 and BCG vaccination policies. These studies were not systematically corrected for confounding variables. We observed that after correction for confounding variables, most notably testing rates, there was no association between BCG vaccination policy and COVD-19 spread rate or percent mortality. Moreover, we found variables describing co-morbidities, including cardiovascular death rate and smoking prevalence, were significantly associated COVID-19 spread rate and percent mortality, respectively. While reporting biases may confound our observations, our epidemiological findings do not provide evidence to correlate overall BCG vaccination policy with the spread of CoV-2 and its associated mortality.
| S-EPMC7591473 | biostudies-literature
Project description:A series of epidemiological explorations has suggested a negative association between national bacillus Calmette-Guérin (BCG) vaccination policy and the prevalence and mortality of coronavirus disease 2019 (COVID-19). However, these comparisons are difficult to validate due to broad differences between countries such as socioeconomic status, demographic structure, rural vs. urban settings, time of arrival of the pandemic, number of diagnostic tests and criteria for testing, and national control strategies to limit the spread of COVID-19. We review evidence for a potential biological basis of BCG cross-protection from severe COVID-19, and refine the epidemiological analysis to mitigate effects of potentially confounding factors (e.g., stage of the COVID-19 epidemic, development, rurality, population density, and age structure). A strong correlation between the BCG index, an estimation of the degree of universal BCG vaccination deployment in a country, and COVID-19 mortality in different socially similar European countries was observed (r 2 = 0.88; P = 8 × 10-7), indicating that every 10% increase in the BCG index was associated with a 10.4% reduction in COVID-19 mortality. Results fail to confirm the null hypothesis of no association between BCG vaccination and COVID-19 mortality, and suggest that BCG could have a protective effect. Nevertheless, the analyses are restricted to coarse-scale signals and should be considered with caution. BCG vaccination clinical trials are required to corroborate the patterns detected here, and to establish causality between BCG vaccination and protection from severe COVID-19. Public health implications of a plausible BCG cross-protection from severe COVID-19 are discussed.
| S-EPMC7395502 | biostudies-literature
Project description:Supersulphides (inorganic and organic sulphides with sulphur catenation) manifest diverse physiological functions. These supersulphides are mainly generated from mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulphide synthase (CPERS). Here we found powerful protective functions of supersulphides in viral airway infections (influenza and COVID-19) and chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and aged lungs. Enhanced supersulphide exhalation also occurred from human airways in COVID-19 as well as the hamster model of SARS-CoV-2 infection, as identified by breath supersulphur-omics that we developed herein. The lung damage related to oxidative stress and inflammation in mouse models of COPD, IPF, and ageing and the lethal effects that resulted were mitigated by endogenous supersulphides, supplied via CARS2/CPERS or exogenously by the supersulphide donor glutathione trisulphide. Our findings thus elucidated the airway protective role of supersulphides and their therapeutic potential in viral and chronic lung diseases.
2023-07-14 | PXD043607 | Pride
Project description:As of recent, the pandemic episode of COVID-19, a severe acute respiratory syndrome brought about by a novel coronavirus (SARS-CoV-2) expanding the pace of mortality, has affected the disease rate profoundly. Invulnerability is the fundamental choice to prevent the ruining event of COVID-19, as the drugs and antibodies are in the phase of preliminary clinical trials. Within this brief period, a few strains of SARS-CoV-2 have been recognized by the vaccine manufacturers, which could be an incorrect guess about the strain that will end up spreading. Since the circulating SARS-CoV-2 strains continue to mutate, immunizations, if at all works, might be for a restricted time. We have not put sufficient time in research to understand the immune responses that correlate with protection as this could help refine vaccines. Here, we have summed up the adequacy of the immunomodulatory component of probiotics for the prevention against viral infections. Furthermore, an in silico data have been provided in support of the "probiotics-derived lipopeptides" role in inactivating spike (S) glycoprotein of SARS-CoV-2 and its host receptor molecule, ACE2. Among well characterized lipopeptides derived from different probiotic strains, subtilisin (Bacillus amyloliquefaciens), curvacin A (Lactobacillus curvatus), sakacin P (Lactobacillus sakei), lactococcin Gb (Lactococcus lactis) was utilized in this study to demonstrate a higher binding proclivity to S-protein of SARS-CoV-2 and human ACE2. The outcome revealed noteworthy capabilities of the lipopeptides, due to their amphiphilic nature, to bind spike protein and receptor molecule, which may act to competitively inhibit the mandatory interaction of SARS-CoV-2 with the host epithelial cell expressing ACE2 for its entry into the cell for reproduction. In the current situation, probiotic treatment alongside chemotherapy may assist in bringing about substantial improvement of the health of COVID-19 patients. At the same time, probiotics may aid towards building up the immune defenses in people to evade COVID-19.
| S-EPMC7680993 | biostudies-literature
Project description:Background There is an urgent need to understand the key events driving pathogenesis of severe COVID-19 disease, so that precise treatment can be instituted. In this respect NETosis is gaining increased attention in the scientific community, as an important pathological process contributing to mortality. We sought to test if indeed there exists robust evidence of NETosis in multiple transcriptomic data sets from human subjects with severe COVID-19 disease. Gene set enrichment analysis was performed to test for up-regulation of gene set functional in NETosis in the blood of patients with COVID-19 illness. Results Blood gene expression functional in NETosis increased with severity of illness, showed negative correlation with blood oxygen saturation, and was validated in the lung of COVID-19 non-survivors. Temporal expression of IL-6 was compared between severe and moderate illness with COVID-19. Unsupervised clustering was performed to reveal co-expression of IL-6 with complement genes. In severe COVID-19 illness, there is transcriptional evidence of activation of NETosis, complement and coagulation cascade, and negative correlation between NETosis and respiratory function (oxygen saturation). An early spike in IL-6 is observed in severe COVID-19 illness that is correlated with complement activation. Conclusions Based on the transcriptional dynamics of IL-6 expression and its downstream effect on complement activation, we constructed a model that links early spike in IL-6 level with persistent and self-perpetuating complement activation, NETosis, immunothrombosis and respiratory dysfunction. Our model supports the early initiation of anti-IL6 therapy in severe COVID-19 disease before the life-threatening complications of the disease can perpetuate themselves autonomously. Supplementary Information The online version contains supplementary material available at 10.1186/s12863-021-01001-1.
| S-EPMC8590626 | biostudies-literature
Project description:Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable.
| S-EPMC7566896 | biostudies-literature
Project description:In December 2019, a new coronavirus, SARS-CoV-2, which causes the respiratory illness that led to the COVID-19 pandemic, was reported. In the face of such a new pathogen, special precautions must be taken to examine potentially infectious materials due to the lack of knowledge on disease transmissibility, infectivity, and molecular pathogenicity. Here, we present a complete and safe workflow for performing scRNA-seq experiments on blood samples of infected patients from cell isolation to data analysis using the micro-well based BD Rhapsody platform. For complete information on the use and execution of this protocol, please refer to Schulte-Schrepping et al. (2020).
| S-EPMC7757730 | biostudies-literature
Project description:The unprecedented generation of large volumes of biodiversity data is consistently contributing to a wide range of disciplines, including disease ecology. Emerging infectious diseases are usually zoonoses caused by multi-host pathogens. Therefore, their understanding may require the access to biodiversity data related to the ecology and the occurrence of the species involved. Nevertheless, despite several data-mobilization initiatives, the usage of biodiversity data for research into disease dynamics has not yet been fully leveraged. To explore current contribution, trends, and to identify limitations, we characterized biodiversity data usage in scientific publications related to human health, contrasting patterns of studies citing the Global Biodiversity Information Facility (GBIF) with those obtaining data from other sources. We found that the studies mainly obtained data from scientific literature and other not aggregated or standardized sources. Most of the studies explored pathogen species and, particularly those with GBIF-mediated data, tended to explore and reuse data of multiple species (>2). Data sources varied according to the taxa and epidemiological roles of the species involved. Biodiversity data repositories were mainly used for species related to hosts, reservoirs, and vectors, and barely used as a source of pathogens data, which was usually obtained from human and animal-health related institutions. While both GBIF- and not GBIF-mediated data studies explored similar diseases and topics, they presented discipline biases and different analytical approaches. Research on emerging infectious diseases may require the access to geographical and ecological data of multiple species. The One Health challenge requires interdisciplinary collaboration and data sharing, which is facilitated by aggregated repositories and platforms. The contribution of biodiversity data to understand infectious disease dynamics should be acknowledged, strengthened, and promoted.
| S-EPMC9880238 | biostudies-literature
Project description:Taking anti-inflammatory drugs, including non-steroidal (NSAIDs), during Covid-19 infection, how much is risky? The French Minister of Health, who has raised an alarm on a possible risk deriving from the use of ibuprofen for the control of fever and other symptoms during the disease, opened the debate a few days ago. In this paper we examine available evidence from preclinical and clinical studies that had analysed the role of COX in the inflammatory process and the effects of NSAIDs in patients with infections. Most of the published studies that suggested not protective effects of NSAIDs were mainly performed in vitro or on animals. Therefore, their meaning in humans is to be considered with great caution. Based also on data suggesting protective effects of NSAIDs, we concluded that currently there is no evidence suggesting a correlation between NSAIDs and a worsening of infections. Further studies will be certainly needed to better define the role of NSAIDs and particularly COX2 inhibitors in patients with infections. In the meantime, we must wait for results of the revision started by the PRAC on May 2019 on the association ibuprofen/ketoprofen?????? and worsening of infections. Since nowadays no scientific evidence establishes a correlation between NSAIDS and worsening of COVID-19, patients should be advice against any NSAIDs self-medication when COVID-19 like symptoms are present.
| S-EPMC7189871 | biostudies-literature