Dataset Information

Dysregulation of the kallikrein-kinin system in bronchoalveolar lavage fluid of patients with severe COVID-19.

ABSTRACT:

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a critical component of the kallikrein-kinin system. Its dysregulation may lead to increased vascular permeability and release of inflammatory chemokines. Interactions between the kallikrein-kinin and the coagulation system might further contribute to thromboembolic complications in COVID-19.

Methods

In this observational study, we measured plasma and tissue kallikrein hydrolytic activity, levels of kinin peptides, and myeloperoxidase (MPO)-DNA complexes as a biomarker for neutrophil extracellular traps (NETs), in bronchoalveolar lavage (BAL) fluid from patients with and without COVID-19.

Findings

In BAL fluid from patients with severe COVID-19 (n = 21, of which 19 were mechanically ventilated), we observed higher tissue kallikrein activity (18·2 pM [1·2-1535·0], median [range], n = 9 vs 3·8 [0·0-22·0], n = 11; p = 0·030), higher levels of the kinin peptide bradykinin-(1-5) (89·6 [0·0-2425·0], n = 21 vs 0·0 [0·0-374·0], n = 19, p = 0·001), and higher levels of MPO-DNA complexes (699·0 ng/mL [66·0-142621·0], n = 21 vs 70·5 [9·9-960·0], n = 19, p < 0·001) compared to patients without COVID-19.

Interpretation

Our observations support the hypothesis that dysregulation of the kallikrein-kinin system might occur in mechanically ventilated patients with severe pulmonary disease, which might help to explain the clinical presentation of patients with severe COVID-19 developing pulmonary oedema and thromboembolic complications. Therefore, targeting the kallikrein-kinin system should be further explored as a potential treatment option for patients with severe COVID-19.

Funding

Research Foundation-Flanders (G0G4720N, 1843418N), KU Leuven COVID research fund.

SUBMITTER: Martens CP

PROVIDER: S-EPMC9352453 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Dysregulation of the kallikrein-kinin system in bronchoalveolar lavage fluid of patients with severe COVID-19.

Martens Caroline P CP Van Mol Pierre P Wauters Joost J Wauters Els E Gangnus Tanja T Noppen Bernard B Callewaert Hanne H Feyen Jean H M JHM Liesenborghs Laurens L Heylen Elisabeth E Jansen Sander S Pereira Leydi Carolina Velásquez LCV Kraisin Sirima S Guler Ipek I Engelen Matthias M MM Ockerman Anna A Van Herck Anke A Vos Robin R Vandenbriele Christophe C Meersseman Philippe P Hermans Greet G Wilmer Alexander A Martinod Kimberly K Burckhardt Bjoern B BB Vanhove Marc M Jacquemin Marc M Verhamme Peter P Neyts Johan J Vanassche Thomas T

EBioMedicine 20220805

<h4>Background</h4>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a critical component of the kallikrein-kinin system. Its dysregulation may lead to increased vascular permeability and release of inflammatory chemokines. Interactions between the kallikrein-kinin and the coagulation system might further contribute to thromboembolic complications in COVID-19.<h4>Methods</h4>In this observational study, we measured plasma a ...[more]

PMID: 35939907

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Dataset Information

Dysregulation of the kallikrein-kinin system in bronchoalveolar lavage fluid of patients with severe COVID-19.

Background

Methods

Findings

Interpretation

Funding

Publications

Dysregulation of the kallikrein-kinin system in bronchoalveolar lavage fluid of patients with severe COVID-19.

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