Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19

Leucker, Thorsten M.; Osburn, William O.; Reventún, Paula; Smith, Kimberley J.; Claggett, Brian; Brouwer, Sophie de; Williams, Marlene S.; Gerstenblith, Gary; Hager, David N.; Streiff, Michael B.; Solomon, Scott D.; Lowenstein, Charles J.

doi:10.1016/j.jacbts.2021.09.013

Cited by 26 publications

(28 citation statements)

References 35 publications

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“…hypertension, smoking, pre-existing diabetes, obesity, and presence of cardiovascular disease) are particularly vulnerable and have adverse outcomes in COVID-19 [54] . Equally important, clinical trials testing whether interventions that ameliorate endothelial dysfunction can have beneficial effects in COVID-19 patients are ongoing 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 and we have obtained very encouraging interim results in a randomized study testing L-Arginine oral supplementation in COVID-19 hospitalized patients [55] .…”

Section: Introductionmentioning

confidence: 90%

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey

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et al. 2022

Pharmacological Research

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Section: Introductionmentioning

confidence: 90%

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey

Izzo

Trimarco

Mone

et al. 2022

Pharmacological Research

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“…The paucity of reports focused on this important topic underscores the necessity for more intensive investigation. Novel platelet-directed therapies currently under investigation include the P-selectin-targeted monoclonal antibody, crizanlizumab (113).…”

Section: Nucleocapsid Proteinmentioning

confidence: 99%

Emerging Role of Platelet-Endothelium Interactions in the Pathogenesis of Severe SARS-CoV-2 Infection-Associated Myocardial Injury

et al. 2022

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Cardiovascular dysfunction and disease are common and frequently fatal complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Indeed, from early on during the SARS-CoV-2 virus pandemic it was recognized that cardiac complications may occur, even in patients with no underlying cardiac disorders, as part of the acute infection, and that these were associated with more severe disease and increased morbidity and mortality. The most common cardiac complication is acute cardiac injury, defined by significant elevation of cardiac troponins. The potential mechanisms of cardiovascular complications include direct viral myocardial injury, systemic inflammation induced by the virus, sepsis, arrhythmia, myocardial oxygen supply-demand mismatch, electrolyte abnormalities, and hypercoagulability. This review is focused on the prevalence, risk factors and clinical course of COVID-19-related myocardial injury, as well as on current data with regard to disease pathogenesis, specifically the interaction of platelets with the vascular endothelium. The latter section includes consideration of the role of SARS-CoV-2 proteins in triggering development of a generalized endotheliitis that, in turn, drives intense activation of platelets. Most prominently, SARS-CoV-2–induced endotheliitis involves interaction of the viral spike protein with endothelial angiotensin-converting enzyme 2 (ACE2) together with alternative mechanisms that involve the nucleocapsid and viroporin. In addition, the mechanisms by which activated platelets intensify endothelial activation and dysfunction, seemingly driven by release of the platelet-derived calcium-binding proteins, SA100A8 and SA100A9, are described. These events create a SARS-CoV-2–driven cycle of intravascular inflammation and coagulation, which contributes significantly to a poor clinical outcome in patients with severe disease.

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“…COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin. Leucker and colleagues tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19 [ 25 ]. In a double-blinded study, hospitalized patients with moderate COVID-19 were randomly assigned to receive either crizanlizumab or placebo.…”

Section: Crizanlizumabmentioning

confidence: 99%

Novel Strategies for the Treatment of COVID-19

McCarthy

2022

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On 4 September, 2020, the US National Institutes of Health launched a new clinical trial, “A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic and Additional Strategies in Hospitalized Adults with COVID-19.” This open-label, placebo-controlled, multicenter, adaptive platform study was designed to evaluate therapeutic options for patients hospitalized with mild, moderate, or severe COVID-19. A variety of drugs and drug classes were selected, including heparin, the monoclonal antibody crizanlizumab, sodium-glucose cotransporter-2 inhibitors, and purinergic signaling receptor Y 12 inhibitors. These medications have been widely used in the treatment of other conditions, from sick cell disease to type 2 diabetes mellitus and some forms of cardiovascular disease, but their inclusion in a study of COVID-19 was somewhat unexpected. This article examines the rationale behind the use of these disparate agents in the treatment and prevention of adverse outcomes in patients with COVID-19 and explores how these strategies may be utilized in the future to address the severe acute respiratory syndrome coronavirus 2 pandemic.

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Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19

Abstract: Visual Abstract

Cited by 26 publications

References 35 publications

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey

Emerging Role of Platelet-Endothelium Interactions in the Pathogenesis of Severe SARS-CoV-2 Infection-Associated Myocardial Injury

Novel Strategies for the Treatment of COVID-19

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