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1.
Sci Rep ; 11(1): 23928, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1585797

ABSTRACT

Identification of transcriptional regulatory mechanisms and signaling networks involved in the response of host cells to infection by SARS-CoV-2 is a powerful approach that provides a systems biology view of gene expression programs involved in COVID-19 and may enable the identification of novel therapeutic targets and strategies to mitigate the impact of this disease. In this study, our goal was to identify a transcriptional regulatory network that is associated with gene expression changes between samples infected by SARS-CoV-2 and those that are infected by other respiratory viruses to narrow the results on those enriched or specific to SARS-CoV-2. We combined a series of recently developed computational tools to identify transcriptional regulatory mechanisms involved in the response of epithelial cells to infection by SARS-CoV-2, and particularly regulatory mechanisms that are specific to this virus when compared to other viruses. In addition, using network-guided analyses, we identified kinases associated with this network. The results identified pathways associated with regulation of inflammation (MAPK14) and immunity (BTK, MBX) that may contribute to exacerbate organ damage linked with complications of COVID-19. The regulatory network identified herein reflects a combination of known hits and novel candidate pathways supporting the novel computational pipeline presented herein to quickly narrow down promising avenues of investigation when facing an emerging and novel disease such as COVID-19.


Subject(s)
COVID-19/genetics , Gene Expression Profiling/methods , SARS-CoV-2/pathogenicity , Sequence Analysis, RNA/methods , A549 Cells , Cell Line , Epithelial Cells/chemistry , Epithelial Cells/cytology , Epithelial Cells/virology , Gene Expression Regulation , Humans , Models, Biological , Systems Biology
3.
PLoS One ; 16(5): e0245031, 2021.
Article in English | MEDLINE | ID: covidwho-1314324

ABSTRACT

SARS-CoV-2 infection causing the novel coronavirus disease 2019 (COVID-19) has been responsible for more than 2.8 million deaths and nearly 125 million infections worldwide as of March 2021. In March 2020, the World Health Organization determined that the COVID-19 outbreak is a global pandemic. The urgency and magnitude of this pandemic demanded immediate action and coordination between local, regional, national, and international actors. In that mission, researchers require access to high-quality biological materials and data from SARS-CoV-2 infected and uninfected patients, covering the spectrum of disease manifestations. The "Biobanque québécoise de la COVID-19" (BQC19) is a pan-provincial initiative undertaken in Québec, Canada to enable the collection, storage and sharing of samples and data related to the COVID-19 crisis. As a disease-oriented biobank based on high-quality biosamples and clinical data of hospitalized and non-hospitalized SARS-CoV-2 PCR positive and negative individuals. The BQC19 follows a legal and ethical management framework approved by local health authorities. The biosamples include plasma, serum, peripheral blood mononuclear cells and DNA and RNA isolated from whole blood. In addition to the clinical variables, BQC19 will provide in-depth analytical data derived from the biosamples including whole genome and transcriptome sequencing, proteome and metabolome analyses, multiplex measurements of key circulating markers as well as anti-SARS-CoV-2 antibody responses. BQC19 will provide the scientific and medical communities access to data and samples to better understand, manage and ultimately limit, the impact of COVID-19. In this paper we present BQC19, describe the process according to which it is governed and organized, and address opportunities for future research collaborations. BQC19 aims to be a part of a global communal effort addressing the challenges of COVID-19.


Subject(s)
Biological Specimen Banks/organization & administration , COVID-19/pathology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , Humans , Information Dissemination/methods , Pandemics , Quebec/epidemiology , SARS-CoV-2/isolation & purification
4.
PLoS One ; 16(5): e0245031, 2021.
Article in English | MEDLINE | ID: covidwho-1234580

ABSTRACT

SARS-CoV-2 infection causing the novel coronavirus disease 2019 (COVID-19) has been responsible for more than 2.8 million deaths and nearly 125 million infections worldwide as of March 2021. In March 2020, the World Health Organization determined that the COVID-19 outbreak is a global pandemic. The urgency and magnitude of this pandemic demanded immediate action and coordination between local, regional, national, and international actors. In that mission, researchers require access to high-quality biological materials and data from SARS-CoV-2 infected and uninfected patients, covering the spectrum of disease manifestations. The "Biobanque québécoise de la COVID-19" (BQC19) is a pan-provincial initiative undertaken in Québec, Canada to enable the collection, storage and sharing of samples and data related to the COVID-19 crisis. As a disease-oriented biobank based on high-quality biosamples and clinical data of hospitalized and non-hospitalized SARS-CoV-2 PCR positive and negative individuals. The BQC19 follows a legal and ethical management framework approved by local health authorities. The biosamples include plasma, serum, peripheral blood mononuclear cells and DNA and RNA isolated from whole blood. In addition to the clinical variables, BQC19 will provide in-depth analytical data derived from the biosamples including whole genome and transcriptome sequencing, proteome and metabolome analyses, multiplex measurements of key circulating markers as well as anti-SARS-CoV-2 antibody responses. BQC19 will provide the scientific and medical communities access to data and samples to better understand, manage and ultimately limit, the impact of COVID-19. In this paper we present BQC19, describe the process according to which it is governed and organized, and address opportunities for future research collaborations. BQC19 aims to be a part of a global communal effort addressing the challenges of COVID-19.


Subject(s)
Biological Specimen Banks/organization & administration , COVID-19/pathology , COVID-19/epidemiology , COVID-19/genetics , COVID-19/metabolism , Humans , Information Dissemination/methods , Pandemics , Quebec/epidemiology , SARS-CoV-2/isolation & purification
5.
PLoS Comput Biol ; 17(3): e1008810, 2021 03.
Article in English | MEDLINE | ID: covidwho-1121603

ABSTRACT

Abnormal coagulation and an increased risk of thrombosis are features of severe COVID-19, with parallels proposed with hemophagocytic lymphohistiocytosis (HLH), a life-threating condition associated with hyperinflammation. The presence of HLH was described in severely ill patients during the H1N1 influenza epidemic, presenting with pulmonary vascular thrombosis. We tested the hypothesis that genes causing primary HLH regulate pathways linking pulmonary thromboembolism to the presence of SARS-CoV-2 using novel network-informed computational algorithms. This approach led to the identification of Neutrophils Extracellular Traps (NETs) as plausible mediators of vascular thrombosis in severe COVID-19 in children and adults. Taken together, the network-informed analysis led us to propose the following model: the release of NETs in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation. This would be a common pathogenic mechanism in conditions including autoimmune/infectious diseases, hematologic and metabolic disorders.


Subject(s)
COVID-19/complications , COVID-19/genetics , Extracellular Traps/genetics , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/genetics , Models, Biological , SARS-CoV-2/genetics , Thrombosis/etiology , Thrombosis/genetics , Algorithms , Cell Degranulation/genetics , Computational Biology , Gene Expression Regulation , Gene Regulatory Networks , Genetic Predisposition to Disease , Humans , Pandemics , Protein Interaction Maps , Pulmonary Embolism/etiology , Pulmonary Embolism/genetics , Viral Proteins/genetics
6.
J Law Biosci ; 7(1): lsaa020, 2020.
Article in English | MEDLINE | ID: covidwho-690685

ABSTRACT

Effective responses to the COVID-19 pandemic require novel solutions for research and responsible data sharing. Biobanking presents itself as a key priority in furthering our understanding of COVID-19. In this article, we propose a tripartite approach to consent to create resources for research relating to COVID-19. The approach aims to link three levels of participation: COVID-19 patients, respiratory/infectious disease patients, and longitudinal study participants. We explore the potential approaches that can be taken to consent processes with these three participant groups. We furthermore describe an access model for both single-site and multi-site data and sample storage. Through dealing with these topics at a high level, the model may be adapted to local legal and ethical requirements while still pursuing its ultimate goal: the creation of a research infrastructure that supports transparent, strong, and open science.

7.
J Exp Med ; 217(6)2020 06 01.
Article in English | MEDLINE | ID: covidwho-72158

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10-15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils-the ability to form neutrophil extracellular traps (NETs)-may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Extracellular Traps , Lung Diseases , Neutrophils/pathology , Pneumonia, Viral/pathology , COVID-19 , Coronavirus Infections/complications , Cytokines/metabolism , Humans , Lung Diseases/etiology , Lung Diseases/metabolism , Lung Diseases/pathology , Pandemics , Pneumonia, Viral/complications , SARS-CoV-2
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