{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T14:35:59Z","timestamp":1771338959205,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012028","name":"Trombosestichting Nederland","doi-asserted-by":"publisher","award":["2020_A"],"award-info":[{"award-number":["2020_A"]}],"id":[{"id":"10.13039\/501100012028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430012010016"],"award-info":[{"award-number":["10430012010016"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10430012010004"],"award-info":[{"award-number":["10430012010004"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>COVID\u201019 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID\u201019, we performed proteomics analysis on SARS\u2010CoV\u20102 infected lung tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liquid chromatography mass spectrometry was performed on SARS\u2010CoV\u20102 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID\u201019 versus influenza) and thrombus morphology (embolism versus <jats:italic>in situ<\/jats:italic>). Influenza autopsy cases with pulmonary thrombi were used as controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to influenza controls, both analyses of COVID\u201019 whole\u2010tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID\u201019 lung tissue. Analysis of isolated COVID\u201019 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that <jats:italic>in situ<\/jats:italic> thrombi have significant upregulation of coronavirus pathogenesis proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The decrease in platelet activation pathways in severe COVID\u201019 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, <jats:italic>in situ<\/jats:italic> thrombi show upregulation of various proteins related to SARS\u2010CoV\u20102 pathogenesis compared to thromboemboli, which may indicate increased <jats:italic>in situ<\/jats:italic> pulmonary thrombosis in COVID\u201019. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of <jats:italic>in situ<\/jats:italic> thrombosis in severe COVID\u201019.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15143","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T04:29:55Z","timestamp":1705984195000},"page":"967-982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Increase in venous thromboembolism in SARS\u2010CoV\u20102 infected lung tissue: proteome analysis of lung parenchyma, isolated endothelium, and thrombi"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9931-0214","authenticated-orcid":false,"given":"Boaz V","family":"Lopuha\u00e4","sequence":"first","affiliation":[{"name":"Department of Pathology Erasmus University Medical Centre  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Co\u015fkun","family":"Guzel","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro\u2010Oncology, Clinical and Cancer Proteomics, Department of Neurology Erasmus University Medical Centre  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anabel","family":"van der Lee","sequence":"additional","affiliation":[{"name":"Vrije Universiteit  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry P P","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus University Medical Centre  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Folkert J","family":"van Kemenade","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus University Medical Centre  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menno V","family":"Huisman","sequence":"additional","affiliation":[{"name":"Department of Thrombosis and Hemostasis Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marieke J H A","family":"Kruip","sequence":"additional","affiliation":[{"name":"Department of Haematology Erasmus University Medical Centre  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theo M","family":"Luider","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro\u2010Oncology, Clinical and Cancer Proteomics, Department of Neurology Erasmus University Medical Centre  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9699-4860","authenticated-orcid":false,"given":"Jan H","family":"von der Th\u00fcsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus University Medical Centre  Rotterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization.The true death toll of COVID\u201019: estimating global excess mortality.2023https:\/\/www.who.int\/data\/stories\/the\u2010true\u2010death\u2010toll\u2010of\u2010covid\u201019\u2010estimating\u2010global\u2010excess\u2010mortality."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.09.020421"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30527-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25982"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12496"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.23.28996"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00665-7"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathmechdis.3.121806.154316"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/viru.25779"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9100133"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01014"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0709-6"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012512"},{"key":"e_1_2_11_15_1","first-page":"785","article-title":"Thrombosis and platelets: an update","volume":"38","author":"Koupenova M","year":"2017","journal-title":"Eur. 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