Repurposing Drugs for the Treatment of COVID-19 and Its Cardiovascular Manifestations

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Abstract

COVID-19 is an infectious disease caused by SARS-CoV-2 leading to the ongoing global pandemic. Infected patients developed a range of respiratory symptoms, including respiratory failure, as well as other extrapulmonary complications. Multiple comorbidities, including hypertension, diabetes, cardiovascular diseases, and chronic kidney diseases, are associated with the severity and increased mortality of COVID-19. SARS-CoV-2 infection also causes a range of cardiovascular complications, including myocarditis, myocardial injury, heart failure, arrhythmias, acute coronary syndrome, and venous thromboembolism. Although a variety of methods have been developed and many clinical trials have been launched for drug repositioning for COVID-19, treatments that consider cardiovascular manifestations and cardiovascular disease comorbidities specifically are limited. In this review, we summarize recent advances in drug repositioning for COVID-19, including experimental drug repositioning, high-throughput drug screening, omics data-based, and network medicine-based computational drug repositioning, with particular attention on those drug treatments that consider cardiovascular manifestations of COVID-19. We discuss prospective opportunities and potential methods for repurposing drugs to treat cardiovascular complications of COVID-19.

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Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

Dawei Wang, Bo Hu, Fangfang Zhu … (2020)

In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Mark Peters (2021)

Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)

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Journal

Journal ID (nlm-ta): Circ Res

Journal ID (iso-abbrev): Circ Res

Journal ID (publisher-id): RES

Title: Circulation Research

Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )

ISSN (Print): 0009-7330

ISSN (Electronic): 1524-4571

Publication date (Electronic): 12 May 2023

Publication date (Print): 12 May 2023

Publication date PMC-release: 12 May 2023

Volume: 132

Issue: 10

Pages: 1374-1386

Affiliations

[1]Channing Division of Network Medicine (R.-S.W., J.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School Boston, MA.

[2]Division of Cardiovascular Medicine (J.L.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School Boston, MA.

Author notes

Ccorrespondence to: Joseph Loscalzo, MD, PhD, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School Boston, 77 Avenue Louis Pasteur, 6th Floor, Room 0630M, Boston, MA 02115. Email jloscalzo@ 123456rics.bwh.harvard.edu

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Joseph Loscalzo https://orcid.org/0000-0002-1153-8047

Article

Accession ID: 00009

DOI: 10.1161/CIRCRESAHA.122.321879

PMC ID: 10171294

PubMed ID: 37167362

SO-VID: 3fd6ee09-0e5e-4ecd-a958-991f0e7704bb

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Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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Keywords: cardiovascular disease,covid-19,drug repositioning,heart failure,myocarditis,thromboembolism

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Keywords: cardiovascular disease, covid-19, drug repositioning, heart failure, myocarditis, thromboembolism

Repurposing Drugs for the Treatment of COVID-19 and Its Cardiovascular Manifestations

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Novel Coronavirus Disease COVID-19

Most cited references 100

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

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