{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:48:20Z","timestamp":1792424900166,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R00HL138272"],"award-info":[{"award-number":["R00HL138272"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG066707"],"award-info":[{"award-number":["R01AG066707"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["3R01AG066707-01S1"],"award-info":[{"award-number":["3R01AG066707-01S1"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>The clinical characteristics and biological effects on the nervous system of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain poorly understood. The aim of this study is to advance epidemiological and mechanistic understanding of the neurological manifestations of coronavirus disease 2019 (COVID-19) using stroke as a case study. In this study, we performed a meta-analysis of clinical studies reporting stroke history, intensive inflammatory response, and procoagulant state C-reactive protein (CRP), Procalcitonin (PCT), and coagulation indicator (D-dimer) in patients with COVID-19. Via network-based analysis of SARS-CoV-2 host genes and stroke-associated genes in the human protein-protein interactome, we inspected the underlying inflammatory mechanisms between COVID-19 and stroke. Finally, we further verified the network-based findings using three RNA-sequencing datasets generated from SARS-CoV-2 infected populations. We found that the overall pooled prevalence of stroke history was 2.98% (95% CI, 1.89\u20134.68;<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>=69.2%) in the COVID-19 population. Notably, the severe group had a higher prevalence of stroke (6.06%; 95% CI 3.80\u20139.52;<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>= 42.6%) compare to the non-severe group (1.1%, 95% CI 0.72\u20131.71;<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>= 0.0%). There were increased levels of CRP, PCT, and D-dimer in severe illness, and the pooled mean difference was 40.7 mg\/L (95% CI, 24.3\u201357.1), 0.07 \u03bcg\/L (95% CI, 0.04\u20130.10) and 0.63 mg\/L (95% CI, 0.28\u20130.97), respectively. Vascular cell adhesion molecule 1 (VCAM-1), one of the leukocyte adhesion molecules, is suspected to play a vital role of SARS-CoV-2 mediated inflammatory responses. RNA-sequencing data analyses of the SARS-CoV-2 infected patients further revealed the relative importance of inflammatory responses in COVID-19-associated neurological manifestations. In summary, we identified an elevated vulnerability of those with a history of stroke to severe COVID-19 underlying inflammatory responses (i.e., VCAM-1) and procoagulant pathways, suggesting monotonic relationships, thus implicating causality.<\/jats:p>","DOI":"10.3389\/fnins.2021.606926","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T06:07:29Z","timestamp":1614146849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation"],"prefix":"10.3389","volume":"15","author":[{"given":"Jiayu","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Jehi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feixiong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing.","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. 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