{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:21:05Z","timestamp":1790742065442,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"FWF Austrian Science Fund","doi-asserted-by":"publisher","award":["W1253"],"award-info":[{"award-number":["W1253"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["860044"],"award-info":[{"award-number":["860044"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Overactivation of the complement system has been characterized in severe COVID-19 cases. Complement components are known to trigger NETosis via the coagulation cascade and have also been reported in human tracheobronchial epithelial cells. In this longitudinal study, we investigated systemic and local complement activation and NETosis in COVID-19 patients that underwent mechanical ventilation. Results confirmed significantly higher baseline levels of serum C5a (24.5 \u00b1 39.0 ng\/mL) and TCC (11.03 \u00b1 8.52 \u00b5g\/mL) in patients compared to healthy controls (p &lt; 0.01 and p &lt; 0.0001, respectively). Furthermore, systemic NETosis was significantly augmented in patients (5.87 (\u00b13.71) \u00d7 106 neutrophils\/mL) compared to healthy controls (0.82 (\u00b10.74) \u00d7 106 neutrophils\/mL) (p &lt; 0.0001). In tracheal fluid, baseline TCC levels but not C5a and NETosis, were significantly higher in patients. Kinetic studies of systemic complement activation revealed markedly higher levels of TCC and CRP in nonsurvivors compared to survivors. In contrast, kinetic studies showed decreased local NETosis in tracheal fluid but comparable local complement activation in nonsurvivors compared to survivors. Systemic TCC and NETosis were significantly correlated with inflammation and coagulation markers. We propose that a ratio comprising systemic inflammation, complement activation, and chest X-ray score could be rendered as a predictive parameter of patient outcome in severe SARS-CoV-2 infections.<\/jats:p>","DOI":"10.3390\/v13122376","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T03:12:56Z","timestamp":1638328376000},"page":"2376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7021-1845","authenticated-orcid":false,"given":"Silke","family":"Huber","sequence":"first","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-5451","authenticated-orcid":false,"given":"Mariam","family":"Massri","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Grasse","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Fleischer","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e1ra","family":"Kellnerov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Harpf","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Knabl","sequence":"additional","affiliation":[{"name":"TyrolPath, 6511 Zams, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Sr.","given":"Ludwig","family":"Knabl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital St. Vinzenz, 6511 Zams, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Heiner","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Medicine, Hospital Reutte, 6600 Reutte, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Kummann","sequence":"additional","affiliation":[{"name":"Department of Radiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Neurauter","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7574-7868","authenticated-orcid":false,"given":"G\u00fcnter","family":"Rambach","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Speth","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6804-442X","authenticated-orcid":false,"given":"Reinhard","family":"W\u00fcrzner","sequence":"additional","affiliation":[{"name":"Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ftaa006","DOI":"10.1093\/femspd\/ftaa006","article-title":"Coronaviruses: A paradigm of new emerging zoonotic diseases","volume":"77","author":"Salata","year":"2019","journal-title":"Pathog. 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