The outcome of critically Ill COVID-19 patients Is linked to thromboinflammation dominated by the kallikrein/kinin system
Blom, Anna M.
Frontiers in Immunology ; 12 (2021). - Art.-Nr. 627579. - eISSN 1664-3224
Link zur Originalveröffentlichunghttps://dx.doi.org/10.3389/fimmu.2021.627579
InstitutionenUKU. Institut für Klinische und Experimentelle Trauma-Immunologie
DokumentversionVeröffentlichte Version (Verlags-PDF)
An 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.
SFB 1149 Teilprojekt A01 / Späte Schrankenstörung nach experimentellem und klinischem Polytrauma / DFG / 251293561 [INST 40/479-2]
Wird ergänzt durchhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.627579/full#supplementary-material
Schlagwörter[GND]: COVID-19 | Komplement <Immunologie> | Blutgerinnung | Fibrinolyse | Prognose
[MeSH]: COVID-19 | Complement activation | Thromboinflammation | Fibrinolysis | Prognosis
[Freie Schlagwörter]: kallikrein/kinin system | complement system | coagulation system
[DDC Sachgruppe]: DDC 610 / Medicine & health
LizenzCC BY 4.0 International
DOI & Zitiervorlage
Nutzen Sie bitte diesen Identifier für Zitate & Links: http://dx.doi.org/10.18725/OPARU-43551