{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:15:11Z","timestamp":1787994911069,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Complement system hyperactivation has been proposed as a potential driver of adverse outcomes in severe acute respiratory syndrome coronavirus 2 infected patients, given prior research of complement deposits found in tissue and blood samples, as well as evidence of clinical improvement with anticomplement therapy. Its role in augmenting thrombotic microangiopathy mediated organ damage has also been implicated in coronavirus disease 2019 (COVID\u201019). This study aimed to examine associations between complement parameters and progression to severe COVID\u201019 illness, as well as correlations with other systems. Blood samples of COVID\u201019 patients presenting to the emergency department (ED) were analyzed for a wide panel of complement and inflammatory biomarkers. The primary outcome was COVID\u201019 severity at index ED visit, while the secondary outcome was peak disease severity over the course of illness. Fifty\u2010two COVID\u201019 patients were enrolled. C3a (<jats:italic>p<\/jats:italic>\u2009=\u20090.018), C3a\/C3 ratio (<jats:italic>p<\/jats:italic>\u2009=\u20090.002), and sC5b\u20109\/C3 ratio (<jats:italic>p<\/jats:italic>\u2009=\u20090.021) were significantly elevated in with severe disease at ED presentation. Over the course of illness, C3a (<jats:italic>p<\/jats:italic>\u2009=\u20090.028) and C3a\/C3 ratio (<jats:italic>p<\/jats:italic>\u2009=\u20090.003) were highest in the moderate severity group. In multivariate regression controlled for confounders, complement hyperactivation failed to predict progression to severe disease. C3a, C3a\/C3 ratio, and sC5b\u20109\/C3 ratio were correlated positively with numerous inflammatory biomarkers, fibrinogen, and VWF:Ag, and negatively with plasminogen and ADAMTS13 activity. We found evidence of complement hyperactivation in COVID\u201019, associated with hyperinflammation and thrombotic microangiopathy. Complement inhibition should be further investigated for potential benefit in patients displaying a hyperinflammatory and microangiopathic phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.27077","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T18:05:49Z","timestamp":1620756349000},"page":"5515-5522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Complement levels at admission as a reflection of coronavirus disease 2019 (COVID\u201019) severity state"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8047-338X","authenticated-orcid":false,"given":"Brandon Michael","family":"Henry","sequence":"first","affiliation":[{"name":"Cardiac Intensive Care Unit, The Heart Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0275-6800","authenticated-orcid":false,"given":"Ivan","family":"Szergyuk","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Jagiellonian University Medical College  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Helena Santos","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Statistics Federal University of Parana  Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lippi","sequence":"additional","affiliation":[{"name":"Section of Clinical Biochemistry University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin L.","family":"Benoit","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Vikse","sequence":"additional","affiliation":[{"name":"Clinical Immunology Unit Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie W.","family":"Benoit","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics, College of Medicine University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2020.04.027"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.05.013"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2020-1284"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-010-1034-0"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2009.139"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0320-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2019.11.004"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-019-04888-5"},{"key":"e_1_2_10_10_1","first-page":"1","article-title":"Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID\u201019 infection: a report of five cases","volume":"220","author":"Magro C","year":"2020","journal-title":"Transl Res J Lab Clin Med"},{"key":"e_1_2_10_11_1","article-title":"Highly pathogenic coronavirus N protein aggravates lung injury by MASP\u20102\u2010mediated complement over\u2010activation","author":"Gao CA","year":"2020","journal-title":"medRxiv"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010540117"},{"issue":"7","key":"e_1_2_10_13_1","first-page":"4040","article-title":"Eculizumab treatment in patients with COVID\u201019: preliminary results from real life ASL Napoli 2 Nord experience","volume":"24","author":"Diurno F","year":"2020","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_10_14_1","unstructured":"World Health Organization. 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