{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T16:14:22Z","timestamp":1768493662477,"version":"3.49.0"},"posted":{"date-parts":[[2021,1,18]]},"group-title":"Pathology","reference-count":11,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,1,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Acute respiratory distress syndrome (ARDS) occurred in ~12% of hospitalized COVID-19 patients in a recent New York City cohort. Pulmonary endothelial dysfunction, characterized by increased expression of inflammatory genes and increased monolayer permeability, is a major component of ARDS. Vascular leak results in parenchymal accumulation of leukocytes, protein, and extravascular water, leading to pulmonary edema, ischemia, and activation of coagulation associated with COVID-19. Endothelial inflammation further contributes to uncontrolled cytokine storm in ARDS. We have recently demonstrated that Kr\u00fcppel-like factor 2 (KLF2), a transcription factor which promotes endothelial quiescence and monolayer integrity, is significantly reduced in experimental models of ARDS. Lung inflammation and high-tidal volume ventilation result in reduced KLF2, leading to pulmonary endothelial dysfunction and acute lung injury. Mechanistically, we found that KLF2 is a potent transcriptional activator of Rap guanine nucleotide exchange factor 3 (RAPGEF3) which orchestrates and maintains vascular integrity. Moreover, KLF2 regulates multiple genome-wide association study (GWAS)-implicated ARDS genes. Whether lung KLF2 is regulated by SARS-CoV-2 infection is unknown. Here we report that endothelial KLF2 is significantly reduced in human lung autopsies from COVID-19 patients, which supports that ARDS due to SARS-CoV-2 is a vascular phenotype possibly attributed to KLF2 down-regulation. We provide additional data demonstrating that KLF2 is down-regulated in SARS-CoV infection in mice.<\/jats:p>","DOI":"10.1101\/2021.01.15.426691","type":"posted-content","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T17:35:17Z","timestamp":1610991317000},"source":"Crossref","is-referenced-by-count":4,"title":["SARS-CoV-2 infection reduces Kr\u00fcppel-Like Factor 2 in human lung autopsy"],"prefix":"10.64898","author":[{"given":"Tzu-Han","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Guzy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Schoettler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayodeji","family":"Adegunsoye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliya","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Sperling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6khan M.","family":"Mutlu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4597-3095","authenticated-orcid":false,"given":"Yun","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080509193214000_2021.01.15.426691v1.1","doi-asserted-by":"crossref","unstructured":"Richardson S , Hirsch JS , Narasimhan M , Crawford JM , McGinn T , Davidson KW , and the Northwell C-RC, Barnaby DP , Becker LB , Chelico JD , Cohen SL , Cookingham J , Coppa K , Diefenbach MA , Dominello AJ , Duer-Hefele J , Falzon L , Gitlin J , Hajizadeh N , Harvin TG , Hirschwerk DA , Kim EJ , Kozel ZM , Marrast LM , Mogavero JN , Osorio GA , Qiu M , Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020.","DOI":"10.1001\/jama.2020.6775"},{"key":"2024080509193214000_2021.01.15.426691v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.015"},{"key":"2024080509193214000_2021.01.15.426691v1.3","doi-asserted-by":"crossref","unstructured":"Ackermann M , Verleden SE , Kuehnel M , Haverich A , Welte T , Laenger F , Vanstapel A , Werlein C , Stark H , Tzankov A , Li WW , Li VW , Mentzer SJ , Jonigk D. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. 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Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. 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