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The Outcome of Critically Ill COVID-19 Patients Is Linked to Thromboinflammation Dominated by the Kallikrein/Kinin System.
Lipcsey, Miklós; Persson, Barbro; Eriksson, Oskar; Blom, Anna M; Fromell, Karin; Hultström, Michael; Huber-Lang, Markus; Ekdahl, Kristina N; Frithiof, Robert; Nilsson, Bo.
  • Lipcsey M; Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
  • Persson B; Hedenstierna Laboratory, Anesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Eriksson O; Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Blom AM; Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Fromell K; Department of Translational Medicine, Lund University, Malmö, Sweden.
  • Hultström M; Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Huber-Lang M; Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
  • Ekdahl KN; Unit for Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
  • Frithiof R; Institute for Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany.
  • Nilsson B; Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Front Immunol ; 12: 627579, 2021.
Article in English | MEDLINE | ID: covidwho-1127985
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Kallikrein-Kinin System / COVID-19 / Inflammation Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.627579

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Kallikrein-Kinin System / COVID-19 / Inflammation Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Limits: Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.627579