About: A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19
Creator	Comhair, Suzy Chan, Timothy Erzurum, Serpil Gack, Michaela Jung, Jae Stappenbeck, Thaddeus Cheng, Feixiong Hou, Yuan Shen, Jiayu Zhou, Yadi Culver, Daniel Eng, Charis Farha, Samar Fiocchi, Claudio Jehi, Lara Kallianpur, Asha Mehra, Reena Zein, Joe
source	PMC; WHO
abstract	The global Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measure revealed underlying pathogenesis for broad COVID-19-associated manifestations. Multi-modal analyses of single-cell RNA-sequencing data showed that co-expression of ACE2 and TMPRSS2 was elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn's disease patients compared to uninflamed tissues, revealing shared pathobiology by COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicated that COVID-19 shared intermediate inflammatory endophenotypes with asthma (including IRAK3 and ADRB2). To prioritize potential treatment, we combined network-based prediction and propensity score (PS) matching observational study of 18,118 patients from a COVID-19 registry. We identified that melatonin (odds ratio (OR) = 0.36, 95% confidence interval (CI) 0.22-0.59) was associated with 64% reduced likelihood of a positive laboratory test result for SARS-CoV-2. Using PS-matching user active comparator design, melatonin was associated with 54% reduced likelihood of SARS-CoV-2 positive test result compared to angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (OR = 0.46, 95% CI 0.24-0.86).
has issue date	2020-07-02(xsd:dateTime)
bibo:doi	10.26434/chemrxiv.12579137
bibo:pmid	32676577
has license	cc-by-nc-nd
sha1sum (hex)	6b4138b96bd01dbbaf99bbc8285bf695c5a81659
schema:url	https://doi.org/10.26434/chemrxiv.12579137
resource representing a document's title	A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19
has PubMed Central identifier	PMC7350981
has PubMed identifier	32676577
schema:publication	ChemRxiv
resource representing a document's body	covid:6b4138b96bd01dbbaf99bbc8285bf695c5a81659#body_text
is schema:about of	named entity 'COVID-19' named entity 'Investigation' named entity 'Network Medicine' named entity 'COVID-19' named entity 'viral genome replication' named entity 'OMIM' named entity 'COPD' named entity 'institutional review board' named entity 'COVID' named entity 'co-expression' named entity 'protein' named entity 'ABCA3' named entity 'COVID' named entity 'dyspnea' named entity 'inflammatory response' named entity 'infection' named entity 'COVID' named entity 'SARS-CoV-2' named entity 'Asthma' named entity 'alveolar' named entity 'SARS2' named entity 'lung' named entity 'glucose metabolism' named entity 'approved drugs' named entity 'virus' named entity 'IRAK3' named entity 'ACE2' named entity 'smokers' named entity 'COVID-19' named entity 'heterogeneity' named entity 'RNA-Seq' named entity 'epithelial cell' named entity 'ACE2' named entity 'rheumatoid arthritis' named entity 'higher risk' named entity 'enrichment analyses' named entity 'cigarette smoking' named entity 'asthma' named entity 'asthma' named entity 'COVID' named entity 'IRAK3' named entity 'metabolites' named entity 'subnetwork' named entity 'cell type' named entity 'clinical features' named entity 'vaccination' named entity 'Coronavirus Disease 2019' named entity 'asthma' named entity 'antiviral' named entity 'CFTR' named entity 'infection' named entity 'SARS-CoV-2' named entity 'co-expression' named entity 'TMPRSS2' named entity 'SARS-COV-2' named entity 'melatonin' named entity 'IRAK3' named entity 'EC50' named entity 'SARS-CoV-2' named entity 'antiviral' named entity 'cardiovascular' named entity 'transcriptome' named entity 'gene' named entity 'orphan disease'

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