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

Martens, Caroline P; Mol, Pierre Van; Wauters, Joost; Wauters, Els; Gangnus, Tanja; Noppen, Bernard; Callewaert, Hanne; Feyen, Jean H.M.; Liesenborghs, Laurens; Heylen, Elisabeth; Jansen, S.L.; Pereira, Leydi Carolina Velásquez; Kraisin, Sirima; Guler, Ipek; Engelen, Matthias M; Ockerman, Anna; Herck, Anke Van; Vos, Robin; Vandenbriele, Christophe; Meersseman, Philippe; Hermans, Greet; Wilmer, Alexander; Martinod, Kimberly; Burckhardt, Bjoern B.; Vanhove, Marc; Jacquemin, Marc; Verhamme, Peter; Neyts, Johan; Vanassche, Thomas

doi:10.1016/j.ebiom.2022.104195

Cited by 18 publications

(19 citation statements)

References 48 publications

(55 reference statements)

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“…Viral proteins were shown to bind to kininogen with subsequent generation of bradykinin ( Savitt et al, 2021 ). Lastly, bradykinin and tissue kallikrein activity was increased in BALF of COVID-19 compared to control patients pointing to a dysregulated KKS in the lungs Martens et al, (2021) .…”

Section: The Role Of the Contact Activation And Kallikrein-kinin Syst...mentioning

confidence: 86%

Targeting thromboinflammation in COVID-19 – A narrative review of the potential of C1 inhibitor to prevent disease progression

Urwyler

Moser²,

Trendelenburg³

et al. 2022

Molecular Immunology

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Section: The Role Of the Contact Activation And Kallikrein-kinin Syst...mentioning

confidence: 86%

Targeting thromboinflammation in COVID-19 – A narrative review of the potential of C1 inhibitor to prevent disease progression

Urwyler

Moser²,

Trendelenburg³

et al. 2022

Molecular Immunology

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“…ACE2 is down-regulated and rendered ineffective by SARS-CoV-2, which may hinder the breakdown of kinin peptides that act on bradykinin receptor 1. Although factor XII (FXII) activation triggers coagulation and creates a feedback loop by activating the kallikrein-kinin pathway, the excessive activation of bradykinin receptor 1 causes hyperinflammatory reactions and pulmonary edema [ 106 ].…”

Section: Discussionmentioning

confidence: 99%

“…According to the varied half-lives of these kinin peptides, per-patient profiles of kinin peptides, in fact, reveal an overall increase in bradykinin-(1-5) levels compared to upstream metabolites. In BAL fluid samples from individuals with severe COVID-19, higher levels of kinin peptides and greater kallikrein activity imply that the dysregulation of the kallikrein-kinin system contributes to pulmonary thromboinflammation [ 106 ].…”

Section: Discussionmentioning

confidence: 99%

Hyperinflammatory Response in COVID-19: A Systematic Review

Silva

Ribeiro

Gouveia

et al. 2023

Viruses

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COVID-19 is a multisystemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The immunopathogenic conditions of the hyperinflammatory response that cause systemic inflammation are extremely linked to its severity. This research sought to review the immunopathological elements that contribute to its progression. This is a systematic review using the PUBMED, LILACS, MEDLINE, and SCIELO databases using articles between May 2020 and July 2022 with the following search terms in conjunction with “AND”: “SARS-CoV-2”; “COVID-19”; “ARDS” and “Cytokine Storm”. The quality appraisal and risk of bias were assessed by the JBI checklists and the Cochrane Collaboration’s RoB 2.0 and ROBINS-I tools, respectively, and the risk of bias for in vitro studies by a pre-defined standard in the literature. The search resulted in 39 articles. The main actors in this response denote SARS-CoV-2 Spike proteins, cellular proteases, leukocytes, cytokines, and proteolytic cascades. The “cytokine storm” itself brings several complications to the host through cytokines such as IL-6 and chemokines (such as CCL2), which influence tissue inflammation through apoptosis and pyroptosis. The hyperinflammatory response causes several unfavorable outcomes in patients, and systemic inflammation caused largely by the dysregulation of the immune response should be controlled for their recovery.

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“…ACE2 regulates the renin-angiotensin-aldosterone system (RAAS), which is involved in blood pressure and vascular resistance regulation, and the kallikrein-kinin system, which regulates vasoactive peptides [8,181]. Therefore, the deregulation of ACE2 can increase kinin activity and result in angioedema [166,182]. A 'kinin storm' may occur due to systemic kallikrein-kinin system activation resulting in increased inflammation, vascular permeability, effusion, and ultimately organ damage.…”

Section: The Effects Of Covid-19 Infection On the Coagulation System ...mentioning

confidence: 99%

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

Khreefa

Barbier

Koksal

et al. 2023

Cells

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The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a significant number of reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although the mechanisms of GI pathogenesis are still being examined, viral components isolated from stool samples of infected patients suggest a potential fecal–oral transmission route. In addition, viral RNA has been detected in blood samples of infected patients, making hematologic dissemination of the virus a proposed route for GI involvement. Angiotensin-converting enzyme 2 (ACE2) receptors serve as the cellular entry mechanism for the virus, and these receptors are particularly abundant throughout the GI tract, making the intestine, liver, and pancreas potential extrapulmonary sites for infection and reservoirs sites for developing mutations and new variants that contribute to the uncontrolled spread of the disease and resistance to treatments. This transmission mechanism and the dysregulation of the immune system play a significant role in the profound inflammatory and coagulative cascades that contribute to the increased severity and risk of death in several COVID-19 patients. This article reviews various potential mechanisms of gastrointestinal, liver, and pancreatic injury.

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

Cited by 18 publications

References 48 publications

Targeting thromboinflammation in COVID-19 – A narrative review of the potential of C1 inhibitor to prevent disease progression

Targeting thromboinflammation in COVID-19 – A narrative review of the potential of C1 inhibitor to prevent disease progression

Hyperinflammatory Response in COVID-19: A Systematic Review

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

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