2020
DOI: 10.20944/preprints202004.0023.v1
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Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach

Abstract: Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in t… Show more

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Cited by 76 publications
(65 citation statements)
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“…The dysregulated kallikrein-kinin system's role remains theoretical in COVID-19; however, if true, AT 1 receptor blockade may be favored (over ACE inhibition) in an attempt to preserve the regulatory mechanisms of this system. [61] While there may still be a key role for ACE inhibition in the context of the current disease that we will elucidate in the following sections, these observations support our decision to narrow the focus of this review to the downstream RAAS modifiers, ARBs.…”
Section: Aceis and Arbsmentioning
confidence: 70%
See 1 more Smart Citation
“…The dysregulated kallikrein-kinin system's role remains theoretical in COVID-19; however, if true, AT 1 receptor blockade may be favored (over ACE inhibition) in an attempt to preserve the regulatory mechanisms of this system. [61] While there may still be a key role for ACE inhibition in the context of the current disease that we will elucidate in the following sections, these observations support our decision to narrow the focus of this review to the downstream RAAS modifiers, ARBs.…”
Section: Aceis and Arbsmentioning
confidence: 70%
“…Increased activity of the kallikrein-kinin system occurs under proinflammatory conditions, [59] specifically bradykinin and des-Arg-BK 9 , which can lead to vascular leakage when unchecked by ACE and ACE2, respectively. This mechanism has been posited to be, at least in part, a cause of cough [60] and pulmonary edema, [61] independent of proposed Ang II induced hydrostatic pressure. The dysregulated kallikrein-kinin system's role remains theoretical in COVID-19; however, if true, AT 1 receptor blockade may be favored (over ACE inhibition) in an attempt to preserve the regulatory mechanisms of this system.…”
Section: Aceis and Arbsmentioning
confidence: 99%
“…This spectrum of abnormalities is highly reminiscent of changes seen in the context of the chronic lung allograft rejection (CLAD) of the restrictive phenotype (restrictive allograft syndrome (RAS)), which we have recently described, and which is presumed to occur secondary to antibody-mediated endothelial damage and complement activation of humoral rejection episodes 13 . Such vascular changes are likely to play a central role in the pathogenesis of COVID-19, and may in part be attributable to dysregulation of the endothelial ACE2 receptor with ensuing bradykinin-dependent local lung edema 14 , as well as a highly pro-thrombotic state, which can manifest itself in the lung as well as in extra-pulmonary tissues 15 . Direct…”
Section: Respiratory Tract Histopathology In Coronavirus Infection (Cmentioning
confidence: 99%
“…A recent manuscript by van de Veerdonk et al notes that as long as the virus persists, there is dysfunction of ACE2 function, leading to the dysregulation of the kinin-kallikrein pathway and thus causing the angioedema [15]. They further propose that blocking the B1 and B2 receptors may be beneficial in reducing the pulmonary edema noted in COVID-19.…”
Section: The Contact System and Coronavirus Infectionsmentioning
confidence: 99%
“…Unfortunately, though B2 receptor antagonists (icatibant) exist, there are presently no B1 receptor antagonists. It would be anticipated that dual B1 and B2 receptor inhibition would be ideal; however, the possibility that inhibiting the kallikreinkinin pathway could be of benefit needs to be excluded [14,15].…”
Section: The Contact System and Coronavirus Infectionsmentioning
confidence: 99%