COVID-19 pathophysiology may be driven by a loss of inhibition of the Renin-Angiotensin-Aldosterone System

Rysz, Susanne; Al-Saadi, Jonathan; Sjöström, Anna; Farm, Maria; Jalde, Francesca Campoccia; Plattén, Michael; Eriksson, Helén; Klein, Margareta; Vargas-Paris, Roberto; Nyrén, Sven; Abdula, Goran; Ouellette, Russell; Granberg, Tobias; Fagerlund, Malin Jonsson; Lundberg, Johan

doi:10.21203/rs.3.rs-32494/v2

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…levels were markedly elevated and linearly associated with viral load and lung injury [4]. Moreover, in a prepublished report currently under journal review, infusion of ANGII in a porcine model rapidly (within hours) induced a clinical syndrome closely reflecting the one seen in COVID-19 patients, including histological changes in the lungs with severe thickening of the alveolar walls, possible hyaline membranes, and clotting of vessels, as previously reported in the human COVID-19 phenotype [5].…”

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confidence: 56%

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Treatment with angiotensin II in COVID-19 patients may not be beneficial

et al. 2020

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Dear Editor, We read with great interest the recent article by Zangrillo et al. regarding infusion of angiotensin II (ANGII) in COVID-19 [1], stating that ANGII vasopressor treatment may be logical in the setting of COVID-19 patients requiring vasopressor support. The authors refer to the ATHOSIII trial as support for the use of ANGII in catecholamine-resistant vasodilatory shock despite the known concern for thrombotic and infectious complications associated with ANGII [2]. In addition, the authors suggest to use ANGII in COVID-19 patients recently exposed to angiotensin-converting enzyme inhibitors. We believe that both these statements raise some concern. SARS-CoV-1 downregulates ACE2 with a subsequent increase in ANGII levels creating a disruption akin to over activating the renin-angiotensin-aldosterone system (RAAS) [3]. In a recent COVID-19 case series, ANGII

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confidence: 56%

“…We suggest that much of the pathophysiology in ICU patients with COVID-19 is potentially driven by a loss of the inhibition of the RAAS, causing supranormal concentrations of ANGII [5]. In our opinion, the use of ANGII in COVID-19 patients is therefore at present most questionable.…”

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confidence: 85%

Treatment with angiotensin II in COVID-19 patients may not be beneficial

et al. 2020

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“…28 In a study of a swine model, it was observed that RAS imbalance can cause diffused alveolar damage, increased coagulation, distorted lung perfusion, reduced blood oxygenation, increased pulmonary arterial pressure, and acute tubular necrosis; which are some shared similarities with the presentation of COVID. 29 Tachycardia, palpitation, orthostatic intolerance, breathlessness, and chest pain are described as a consequence of autonomic dysfunction which can be attributed to the destruction of the nervous system by immune cells or by viral particles. These symptoms may also be caused by deconditioning, and hypovolemia.…”

Section: Pathophysiologymentioning

confidence: 99%

Long COVID and its effects on the cardiovascular system: a literature review

Itua¹,

Chukwuka²

2022

Int J Res Med Sci

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A significant cardiac burden exists post COVID-19. This is evident by persistent chest pain, palpitations, dyspnea, exertional fatigue, presence of new-onset heart failure or arrhythmia. Persistent COVID-19 symptoms in the cardiovascular system may be caused by a combination of processes that either increase inflammation or tamper with the autonomic nervous system. The inflammation can be caused by viral load persistence leading to tissue damage. The presence of cytokines and chemokines results in a state of hyper inflammation, immune exhaustion, organ damage during the infectious state and post-viral autoimmunity. The current review aims to discuss the risk factors, pathophysiology and treatment of the protracted form of COVID-19 in relation to the cardiovascular system.

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Are losartan and imatinib effective against SARS-CoV2 pathogenesis? A pathophysiologic-based in silico study

Nejat

Sadr

2020

In Silico Pharmacol.

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Proposing a theory about the pathophysiology of cytokine storm in COVID19, we were to find the potential drugs to treat this disease and to find any effect of these drugs on the virus infectivity through an in silico study. COVID-19-induced ARDS is linked to a cytokine storm phenomenon not explainable solely by the virus infectivity. Knowing that ACE2, the hydrolyzing enzyme of AngII and SARS-CoV2 receptor, downregulates when the virus enters the host cells, we hypothesize that hyperacute AngII upregulation is the eliciting factor of this ARDS. We were to validate this theory through reviewing previous studies to figure out the role of overzealous activation of AT1R in ARDS. According to this theory losartan may attenuate ARDS in this disease. Imatinib, has previously been elucidated to be promising in modulating lung inflammatory reactions and virus infectivity in SARS and MERS. We did an in silico study to uncover any probable other unconsidered inhibitory effects of losartan and imatinib against SARS-CoV2 pathogenesis. Reviewing the literature, we could find that over-activation of AT1R could explain precisely the mechanism of cytokine storm in COVID19. Our in silico study revealed that losartan and imatinib could probably: (1) decline SARS-CoV2 affinity to ACE2. (2) inhibit the main protease and furin, (3) disturb papain-like protease and p38MAPK functions. Our reviewing on renin-angiotensin system showed that overzealous activation of AT1R by hyper-acute excess of AngII due to acute downregulation of ACE2 by SARS-CoV2 explains precisely the mechanism of cytokine storm in COVID-19. Besides, based on our in silico study we concluded that losartan and imatinib are promising in COVID19.

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COVID-19 pathophysiology may be driven by a loss of inhibition of the Renin-Angiotensin-Aldosterone System

Cited by 4 publications

References 22 publications

Treatment with angiotensin II in COVID-19 patients may not be beneficial

Treatment with angiotensin II in COVID-19 patients may not be beneficial

Long COVID and its effects on the cardiovascular system: a literature review

Are losartan and imatinib effective against SARS-CoV2 pathogenesis? A pathophysiologic-based in silico study

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