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AuthorLipcsey, Miklósdc.contributor.author
AuthorPersson, Barbrodc.contributor.author
AuthorEriksson, Oskardc.contributor.author
AuthorBlom, Anna M.dc.contributor.author
AuthorFromell, Karindc.contributor.author
AuthorHultström, Michaeldc.contributor.author
AuthorHuber-Lang, Markusdc.contributor.author
AuthorEkdahl, Kristina N.dc.contributor.author
AuthorFrithiof, Robertdc.contributor.author
AuthorNilsson, Bodc.contributor.author
Date of accession2022-06-28T13:55:42Zdc.date.accessioned
Available in OPARU since2022-06-28T13:55:42Zdc.date.available
Date of first publication2021-02-22dc.date.issued
AbstractAn important manifestation of severe COVID-19 is the ARDS-like lung injury that is associated with vascular endothelialitis, thrombosis, and angiogenesis. The intravascular innate immune system (IIIS), including the complement, contact, coagulation, and fibrinolysis systems, which is crucial for recognizing and eliminating microorganisms and debris in the body, is likely to be involved in the pathogenesis of COVID-19 ARDS. Biomarkers for IIIS activation were studied in the first 66 patients with COVID-19 admitted to the ICU in Uppsala University Hospital, both cross-sectionally on day 1 and in 19 patients longitudinally for up to a month, in a prospective study. IIIS analyses were compared with biochemical parameters and clinical outcome and survival. Blood cascade systems activation leading to an overreactive conjunct thromboinflammation was demonstrated, reflected in consumption of individual cascade system components, e.g., FXII, prekallikrein, and high molecular weight kininogen and in increased levels of activation products, e.g., C4d, C3a, C3d,g, sC5b-9, TAT, and D-dimer. Strong associations were found between the blood cascade systems and organ damage, illness severity scores, and survival. We show that critically ill COVID-19 patients display a conjunct activation of the IIIS that is linked to organ damage of the lung, heart, kidneys, and death. We present evidence that the complement and in particular the kallikrein/kinin system is strongly activated and that both systems are prognostic markers of the outcome of the patients suggesting their role in driving the inflammation. Already licensed kallikrein/kinin inhibitors are potential drugs for treatment of critically ill patients with COVID-19.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseCC BY 4.0 Internationaldc.rights
Link to license texthttps://creativecommons.org/licenses/by/4.0/dc.rights.uri
Keywordkallikrein/kinin systemdc.subject
Keywordcomplement systemdc.subject
Keywordcoagulation systemdc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHCOVID-19dc.subject.mesh
MeSHComplement activationdc.subject.mesh
MeSHThromboinflammationdc.subject.mesh
MeSHFibrinolysisdc.subject.mesh
MeSHPrognosisdc.subject.mesh
TitleThe outcome of critically Ill COVID-19 patients Is linked to thromboinflammation dominated by the kallikrein/kinin systemdc.title
Resource typeWissenschaftlicher Artikeldc.type
SWORD Date2021-03-08T06:44:19Zdc.date.updated
VersionpublishedVersiondc.description.version
DOIhttp://dx.doi.org/10.18725/OPARU-43551dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-43627-2dc.identifier.urn
GNDCOVID-19dc.subject.gnd
GNDKomplement <Immunologie>dc.subject.gnd
GNDBlutgerinnungdc.subject.gnd
GNDFibrinolysedc.subject.gnd
GNDPrognosedc.subject.gnd
InstitutionUKU. Institut für Klinische und Experimentelle Trauma-Immunologieuulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
DOI of original publication10.3389/fimmu.2021.627579dc.relation1.doi
Source - Title of sourceFrontiers in Immunologysource.title
Source - Place of publicationFrontiers Mediasource.publisher
Source - Volume12source.volume
Source - Year2021source.year
Source - Article number627579source.articleNumber
Source - eISSN1664-3224source.identifier.eissn
Open AccessDOAJ Gold, Green Publisheduulm.OA
WoS000626029400001uulm.identifier.wos
Bibliographyuulmuulm.bibliographie
Is Supplemented Byhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.627579/full#supplementary-materialdc.relation.isSupplementedBy
DFG project uulmSFB 1149 Teilprojekt A01 / Späte Schrankenstörung nach experimentellem und klinischem Polytrauma / DFG / 251293561 [INST 40/479-2]uulm.projectDFG


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