{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:45:24Z","timestamp":1790379924449,"version":"4.1.0"},"posted":{"date-parts":[[2020,7,1]]},"reference-count":0,"publisher":"American Chemical Society (ACS)","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000016","name":"United States Department of Health and Human Services","doi-asserted-by":"publisher","award":["361890"],"award-info":[{"award-number":["361890"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"United States Department of Health and Human Services","doi-asserted-by":"publisher","award":["361967"],"award-info":[{"award-number":["361967"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                  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\n                  <jats:italic toggle=\"yes\">ACE2<\/jats:italic>\n                  and\n                  <jats:italic toggle=\"yes\">TMPRSS2<\/jats:italic>\n                  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\n                  <jats:italic toggle=\"yes\">IRAK3<\/jats:italic>\n                  and\n                  <jats:italic toggle=\"yes\">ADRB2<\/jats:italic>\n                  ). 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).\n                <\/jats:p>","DOI":"10.26434\/chemrxiv.12579137.v1","type":"posted-content","created":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:50:42Z","timestamp":1593651042000},"source":"Crossref","is-referenced-by-count":33,"title":["A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19"],"prefix":"10.26434","author":[{"given":"Yadi","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha","family":"Kalianpur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Zein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Culver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar","family":"Farha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy","family":"Comhair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Fiocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"U. Gack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaddeus","family":"S Stappenbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae","family":"U. Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Jehi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serpil","family":"Erzurum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1736-2847","authenticated-orcid":false,"given":"Feixiong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Cleveland Clinic","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/chemrxiv.org\/doi\/pdf\/10.26434\/chemrxiv.12579137.v1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:57:32Z","timestamp":1778752652000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemrxiv.org\/doi\/full\/10.26434\/chemrxiv.12579137.v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,1]]},"references-count":0,"aliases":["10.26434\/chemrxiv.12579137"],"URL":"https:\/\/doi.org\/10.26434\/chemrxiv.12579137.v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1371\/journal.pbio.3000970","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2020,7,1]]},"subtype":"preprint"}}