Blocking mineralocorticoid receptor with spironolactone may have a wide range of therapeutic actions in severe COVID-19 disease

Liaudet, Lucas; Szabó, Csaba

doi:10.1186/s13054-020-03055-6

Cited by 38 publications

(37 citation statements)

References 5 publications

(10 reference statements)

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“…Moreover, a recent study indicated that SARS-CoV-2 infection could downregulate ACE2 at the mRNA level and this effect requires action directly on the ACE2 promoter [ 71 ]. In consistent with the identification of platelet ACE2 in our results, Zaid et al also found that ACE2 mRNA was presented in platelets from both healthy people and COVID-19 patients [ 72 ].…”

Section: Discussionsupporting

confidence: 91%

SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

et al. 2020

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Background: Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear. Methods: Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl 3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.

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Section: Discussionsupporting

confidence: 91%

SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

et al. 2020

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“…However, the ACE2 shedding mechanism by which ADAM17 may prevent COVID-19 infection needs further evaluation (Palau et al, 2020). Aldosterone antagonists, including spironolactone and eplerenone, may have a dual therapeutic mechanism by 1) inhibiting activation of the mineralocorticoid receptor (MR) that promotes the hyperinflammatory profile responsible for ARDS in COVID-19 and 2) inhibiting TMPRSS2 expression, which is essential for activation of the spike protein used in viral entry (Liaudet and Szabo, 2020). Theoretically, aldosterone antagonists may have a beneficial effect in preventing lung injury from COVID-19, however; their benefits in the CV system still remains undetermined.…”

Section: Raas Modulators (Arb Ace Inhibitors Aldosterone Blockers)mentioning

confidence: 99%

Cardiovascular system and COVID-19: manifestations and therapeutics

Mahenthiran¹,

Mahenthiran²,

Mahenthiran³

2020

Reviews in Cardiovascular Medicine

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The world is currently in the midst of a daunting global pandemic due to SARS-CoV-2 viral infection and associated COVID-19 disease. Healthcare professionals are tasked with the challenge of managing diverse multisystem clinical manifestations of this infection. Although acute hypoxic respiratory failure is the hallmark of severe COVID-19 disease, there have been diverse manifestations within the cardiovascular (CV) system that each pose unique therapeutic challenges. Of these manifestations, myocardial injury and right ventricular dysfunction are the most common, however, heart failure, circulatory shock, cardiomyopathy, arrhythmia, and vascular thrombosis have been noted as well. Furthermore, these CV related manifestations portend greater morbidity and mortality, which requires clinicians to be familiar with the most recent information to provide informed patient care. Although there are limited treatment options available for COVID-19, it is imperative that the potential cardiovascular implications of these therapies are considered in these patients. This review highlights the pathophysiological mechanisms of and therapeutics for CV manifestations of COVID-19 as well as the CV implications of proposed COVID-19 therapies. Since our hospital-based providers are the frontline caregivers battling this pandemic, the aim of this review is to assist with clinical decision-making for optimal patient outcomes while maintaining a safe environment for healthcare personnel.

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“…Поэтому, как видно из рисунка 3, спиронолактон, как антиандрогенный препарат, уменьшая содержание тестостерона и блокируя андрогеновые рецепторы, способен уменьшать и экспрессию рецепторов АПФ-2 и, одновременно, активность TМPRSS-2. Поэтому в дополнение к антифибротическим и антигипертензивным свойствам можно рассматривать спиронолактон в качестве противовирусного препарата в лечении COVID-19 [56]. Еще одним важным свойством спиронолактона при лечении хронической сердечной недостаточности и при нарушении функции почек является способность препарата увеличивать уровень калия [57,58].…”

Section: вирусемияunclassified

Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)”

et al. 2020

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The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.

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Blocking mineralocorticoid receptor with spironolactone may have a wide range of therapeutic actions in severe COVID-19 disease

Cited by 38 publications

References 5 publications

SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

Cardiovascular system and COVID-19: manifestations and therapeutics

Combination therapy at an early stage of the novel coronavirus infection (COVID-19). Case series and design of the clinical trial “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)”

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