Amiodarone in the COVID-19 Era: Treatment for Symptomatic Patients Only, or Drug to Prevent Infection?

Sanchís-Gomar, Fabián; Lavie, Carl J.; Morin, Daniel P.; Pérez-Quilis, Carme; Laukkanen, Jari A.; Pérez, Marco

doi:10.1007/s40256-020-00429-7

Cited by 23 publications

(18 citation statements)

References 29 publications

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“…Recently, the case of a patient affected by COVID-19-related respiratory failure who recovered after only supportive measures and off-label short therapy with amiodarone (starting on the second day from admission and lasting 5 days; administered on day 1 as a 15 mg/kg/24 h intravenous infusion, followed by oral administration of 400 mg twice daily) has been reported ( Castaldo et al, 2020 ). Accordingly, amiodarone, widely prescribed to treat both ventricular and supraventricular arrhythmias, has been proposed as a possible therapy (alone or as part of a combination regimen) to prevent SARS-CoV-2 infection rather than to treat symptomatic or severe COVID-19 patients ( Aimo et al, 2020 ; Sanchis-Gomar et al, 2020 ).…”

Section: Sigma-1 Receptor Ligands Exert Antiviral Activitymentioning

confidence: 99%

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

Vela

2020

Front. Pharmacol.

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Outbreaks of emerging infections, such as COVID-19 pandemic especially, confront health professionals with the unique challenge of treating patients. With no time to discover new drugs, repurposing of approved drugs or in clinical development is likely the only solution. Replication of coronaviruses (CoVs) occurs in a modified membranous compartment derived from the endoplasmic reticulum (ER), causes host cell ER stress and activates pathways to facilitate adaptation of the host cell machinery to viral needs. Accordingly, modulation of ER remodeling and ER stress response might be pivotal in elucidating CoV-host interactions and provide a rationale for new therapeutic, host-based antiviral approaches. The sigma-1 receptor (Sig-1R) is a ligand-operated, ER membrane-bound chaperone that acts as an upstream modulator of ER stress and thus a candidate host protein for host-based repurposing approaches to treat COVID-19 patients. Sig-1R ligands are frequently identified in in vitro drug repurposing screens aiming to identify antiviral compounds against CoVs, including severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Sig-1R regulates key mechanisms of the adaptive host cell stress response and takes part in early steps of viral replication. It is enriched in lipid rafts and detergent-resistant ER membranes, where it colocalizes with viral replicase proteins. Indeed, the non-structural SARS-CoV-2 protein Nsp6 interacts with Sig-1R. The activity of Sig-1R ligands against COVID-19 remains to be specifically assessed in clinical trials. This review provides a rationale for targeting Sig-1R as a host-based drug repurposing approach to treat COVID-19 patients. Evidence gained using Sig-1R ligands in unbiased in vitro antiviral drug screens and the potential mechanisms underlying the modulatory effect of Sig-1R on the host cell response are discussed. Targeting Sig-1R is not expected to reduce dramatically established viral replication, but it might interfere with early steps of virus-induced host cell reprogramming, aid to slow down the course of infection, prevent the aggravation of the disease and/or allow a time window to mature a protective immune response. Sig-1R-based medicines could provide benefit not only as early intervention, preventive but also as adjuvant therapy.

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Section: Sigma-1 Receptor Ligands Exert Antiviral Activitymentioning

confidence: 99%

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

Vela

2020

Front. Pharmacol.

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“…Drug repurposing is a popular exploratory method, including exploring new indications from old drugs [ 99 ]. Currently, most of the drugs clinically used to fight the virus are for influenza, viral hepatitis, and HIV, as well as drugs developed for MERS and SARS [ 100 - 170 ] ( Supplementary Table 1 ). However, since the viral outbreak, many exploratory clinical trials of antiviral treatments have been published.…”

Section: Current Therapeutics and Drug Developmentmentioning

confidence: 99%

A Comprehensive Summary of the Knowledge on COVID-19 Treatment

Peng¹,

Tao²,

Satyanarayanan³

et al. 2021

Aging and disease

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“…Amiodarone, used to control a wide range of atrial and ventricular arrhythmias, has been suggested as potential drug for prevention or treatment of COVID-19 [92,98]. The ReCOVery-SIRIO, a multicenter study, aims to determine the role of amiodarone or verapamil, in hospitalised patients within the initial stage of COVID-19 [93,95].…”

Section: Antiarrhythmic Drugs (Other Than Beta-blockers)mentioning

confidence: 99%

“…Use of antiarrhythmic drugs in COVID-19 should be similar to patients in other diseases [98,101]. Dose adjustments may be needed in older patients, and with renal or hepatic impairment [92,102].…”

Section: In Conclusionmentioning

confidence: 99%

Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications

et al. 2021

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Purpose In the pathogenesis of severe COVID-19 complications, derangements of renin–angiotensin–aldosterone system (RAAS), vascular endothelial dysfunction leading to inflammation and coagulopathy, and arrhythmias play an important role. Therefore, it is worth considering the use of currently available drugs to protect COVID-19 patients with cardiovascular diseases. Methods We review the current experience of conventional cardiovascular drugs [angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, anticoagulants, acetosalicylic acid, antiarrhythmic drugs, statins] as well as some other drug classes (antidiabetic drugs, vitamin D and NSAIDs) frequently used by older patients with cardiovascular diseases. Data were sought from clinical databases for COVID-19 and appropriate key words. Conclusions and recommendations are based on a consensus among all authors. Results Several cardiovascular drugs have a potential to protect patients with COVID-19, although evidence is largely based on retrospective, observational studies. Despite propensity score adjustments used in many analyses observational studies are not equivalent to randomised controlled trials (RCTs). Ongoing RCTs include treatment with antithrombotics, pulmonary vasodilators, RAAS-related drugs, and colchicine. RCTs in the acute phase of COVID-19 may not, however, recognise the benefits of long term anti-atherogenic therapies, such as statins. Conclusions Most current cardiovascular drugs can be safely continued during COVID-19. Some drug classes may even be protective. Age-specific data are scarce, though, and conditions which are common in older patients (frailty, comorbidities, polypharmacy) must be individually considered for each drug group.

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Amiodarone in the COVID-19 Era: Treatment for Symptomatic Patients Only, or Drug to Prevent Infection?

Cited by 23 publications

References 29 publications

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?

A Comprehensive Summary of the Knowledge on COVID-19 Treatment

Protecting older patients with cardiovascular diseases from COVID-19 complications using current medications

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