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The Outcome of Crit...
The Outcome of Critically Ill COVID-19 Patients Is Linked to Thromboinflammation Dominated by the Kallikrein/Kinin System
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- Lipcsey, Miklós (author)
- Uppsala universitet,Uppsala University,Anestesiologi och intensivvård,Hedenstiernalaboratoriet,Uppsala Univ, Dept Surg Sci Anesthesiol & Intens Care, Uppsala, Sweden.;Uppsala Univ, Dept Surg Sci, Anesthesiol & Intens Care, Hedenstierna Lab, Uppsala, Sweden.
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- Persson, Barbro (author)
- Uppsala universitet,Uppsala University,Klinisk immunologi
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- Eriksson, Oskar, 1984- (author)
- Uppsala universitet,Uppsala University,Koagulation och inflammationsvetenskap,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
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- Blom, Anna M. (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups,Lund Univ, Dept Translat Med, Malmö, Sweden.
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- Fromell, Karin (author)
- Uppsala universitet,Uppsala University,Klinisk immunologi
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- Hultström, Michael, 1978- (author)
- Uppsala universitet,Uppsala University,Integrativ Fysiologi,Anestesiologi och intensivvård
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- Huber-Lang, Markus (author)
- University Hospital Ulm, Germany,University Hospital of Ulm,Univ Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany.
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- Nilsson Ekdahl, Kristina (author)
- Uppsala universitet,Linnaeus University,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Uppsala University, Sweden,Linnaeus Ctr Biomat Chem, BMC,Klinisk immunologi,Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.
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- Frithiof, Robert (author)
- Uppsala universitet,Uppsala University,Anestesiologi och intensivvård,Hedenstiernalaboratoriet
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- Nilsson, Bo (author)
- Uppsala universitet,Uppsala University,Klinisk immunologi,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2021-02-22
- 2021
- English.
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- thromboinflammation
- kallikrein
- kinin system
- complement system
- coagulation system
- fibrinolysis system
- COVID-19
- prognosis
- Immunologi
- Immunology
- coagulation system
- complement system
- COVID-19
- fibrinolysis system
- kallikrein/kinin system
- prognosis
- thromboinflammation
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lipcsey, Miklós
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Persson, Barbro
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Eriksson, Oskar, ...
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Blom, Anna M.
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Fromell, Karin
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Hultström, Micha ...
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show more...
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Huber-Lang, Mark ...
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Nilsson Ekdahl, ...
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Frithiof, Robert
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Nilsson, Bo
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Frontiers in Imm ...
- By the university
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Linnaeus University
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Lund University
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Uppsala University