key: cord-0783806-mfq3n2ql authors: Jacinto, Jomel Patrick; Patel, Milan; Goh, Justin; Yamamura, Kenneth title: Remdesivir-induced Symptomatic Bradycardia in the treatment of COVID-19 Disease date: 2021-05-15 journal: HeartRhythm Case Rep DOI: 10.1016/j.hrcr.2021.05.004 sha: fab4f82f2a2b159cb20d53f3ef0b679dfbfe4dfc doc_id: 783806 cord_uid: mfq3n2ql nan Authors: Jomel Patrick Jacinto, DO (Corresponding Author) • HCA Healthcare/USF Morsani College of Medicine GME Programs at Regional Medical Center Bayonet Point Remdesivir is an internationally approved broad-spectrum antiviral that has shown promising results in the treatment of COVID-19-related lower respiratory infections by shortening time to recovery compared to placebo (2) . The safety profile of remdesivir was recently evaluated since its emergence; however, there is limited peer-reviewed literature that describe cardiovascular adverse effects such as hemodynamic and electrocardiogram changes related to remdesivir administration. These adverse effects reported in recent available safety data publications include only hypotension (7.5%, 4 out of 53 patients) and atrial fibrillation (5.6%, 3 out of 53 patients). In further discussion of safety, the most commonly reported adverse events were increased liver enzymes, diarrhea, rash, and renal impairment (1, 3) . To the best of our knowledge, there have not been any reported cases of remdesivir-induced hemodynamically unstable sinus bradycardia. Remdesivir is a prodrug that is subsequently metabolized to nucleoside triphosphate once it is transported intracellularly via enzymatic reactions. The mechanism of its metabolite is to inhibit the SARS-CoV-2 RNA-dependent RN polymerase, an enzyme used for viral replication (4). One of the leading theories of how remdesivir can induce sinus node dysfunction is based on its active metabolized triphosphate form and how it closely resembles adenosine 5'-triphosphate (ATP) structurally (5) . ATP and its metabolized form of adenosine is known to exert negative chronotropic and dromotropic effects on sinus node automaticity and AV nodal conduction. This effect is mediated by ATP's ability to suppress the sinus and AV nodes by transiently enhancing vagal tone in the heart (6) (7) (8) . Therefore, it can be postulated that the remdesivir metabolite may exert the same deleterious effects on the conduction system J o u r n a l P r e -p r o o f In a review of related cases, we identified three case reports that reported remdesivir as a cause for acute normotensive marked sinus bradycardia . This was observed only after the initiation of remdesivir treatment with all cases having resolution of bradycardia when remdesivir was discontinued (4 ,8-9) . No cases thus far have described the development of sinus node dysfunction or cardiogenic shock associated with remdesivir treatment In our case report, the patient lacked any prior cardiac history and had normal telemetry monitor and EKG findings prior to remdesivir administration. Furthermore, the patient did not receive any other medications that could have caused her bradycardia. Dexamethasone and remdesivir were started simultaneously as a 10-day and 5-day course, respectively. While dexamethasone is known to cause bradycardia, it was not considered the cause because it resolved upon finishing the remdesivir course while dexamethasone was given for a full 10-day course. To further evaluate remdesivir's likelihood of precipitating the observed clinical event, the Naranjo scoring system, or adverse drug reaction probability scale, was utilized. This scoring system is used to assess the potential causal relationship between clinical events and the drug in question (10, 11) . Our patient scored a 7 out of 10 total points, inferring that the use of remdesivir in this patient's case was the probable culprit of her hemodynamic changes and marked sinus bradycardia, given its abrupt onset with administration and rapid complete resolution on discontinuation. Remdesivir is currently at the forefront of treatment in COVID-19 disease given its overall results in mortality benefit and favorable safety data. There are currently no case reports that have linked remdesivir with hemodynamically significant sinus node dysfunction. With the J o u r n a l P r e -p r o o f 6 proliferation of remdesivir as a mainstay therapy for COVID-19, further investigations are needed to elucidate its effect on the cardiac conduction system. EKG during symptomatic bradycardia revealing EKG on admission prior to remdesivir treatment Telemetry strip obtained over 24 hours after final dose of remdesivir This research was supported in part by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. J o u r n a l P r e -p r o o f Safety profile of the antiviral drug remdesivir: An update Remdesivir for the treatment of covid-19 -final Report: NEJM. Retrieved Compassionate Use of Remdesivir for Patients with Severe Covid-19 Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19 Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns. Clinical Microbiology and Infection Marked Sinus Bradycardia Associated With Remdesivir in COVID-19: A Case and Literature Review. JACC Case Rep Anatomic-Functional Correlates of Adenosine-5'-Triphosphate Triggered Vagal Depressor Reflex Cardiac Adverse Events With Remdesivir in COVID-19 Infection Severe sinus bradycardia associated with Remdesivir in a child with severe SARS-CoV-2 infection Improving the assessment of adverse drug reactions using the Naranjo Algorithm in daily practice: The Japan Adverse Drug Events Study. Bps publications LiverTox: Clinical and Research Information on Drug-Induced Liver Injury National Institute of Diabetes and Digestive and Kidney Diseases