Sinus Bradycardia in Children Treated With Remdesivir for COVID-19

Eleftheriou, Irini; Liaska, Marianthi; Krepis, Panagiotis; Dasoula, Foteini; Dimopoulou, Dimitra; Spyridis, Νikos; Τσολιά, Μαρία

doi:10.1097/inf.0000000000003214

Cited by 13 publications

(12 citation statements)

References 4 publications

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“…The episodes of sinus bradycardia after the third application of remdesivir could probably be drug related, as supposed by recent reports. 11 After this one-off event during therapy with remdesivir, there were no further cardiac events. 12 13 Cardiac involvement has been reported in cases with NCL disease, especially in teenagers and adolescents with juvenile CLN3 disease.…”

Section: Discussionmentioning

confidence: 91%

Therapeutic Management of COVID-19 in a Pediatric Patient with Neurodegenerative CLN2 Disease and ICV—Enzyme Replacement Therapy: A Case Report

et al. 2022

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The 12 years old male patient presented here suffers from neuronal ceroid lipofuscinoses 2 (CLN2) (MIM# 204500) and receives intracerebroventricular enzyme replacement therapy (ICV-ERT) every 14 days. After the emergence of the coronavirus disease 2019 (COVID-19) pandemic, routine care of children and adolescents with rare chronic diseases has become challenging. Although, in general, children do not develop severe COVID-19, when severe acute respiratory syndrome coronavirus 2infection was detected by polymerase chain reaction-screening examination in our CLN2 patient before hospital admission for ICV-ERT, he was regarded to be at risk. Upon diagnosis, the patient developed respiratory deterioration symptoms and was admitted to our pediatric intensive care unit to receive oxygen, remdesivir, and steroids. As far as we know, this is the first CLN2 patient receiving intraventricular enzyme therapy with COVID-19 who required intensive care treatment and specific therapy.

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Section: Discussionmentioning

confidence: 91%

Therapeutic Management of COVID-19 in a Pediatric Patient with Neurodegenerative CLN2 Disease and ICV—Enzyme Replacement Therapy: A Case Report

et al. 2022

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“…Pediatric patients have also exhibited asymptomatic SB after treatment with RDV for COVID-19. In a series of four children treated with ampicillin, RDV, and dexamethasone for COVID-19, three patients (median age 11.5 years) developed asymptomatic SB that resolved within 24 h of treatment completion or RDV discontinuation [ 23 ]. The youngest reported case of bradycardia after RDV administration was identified within this study.…”

Section: Resultsmentioning

confidence: 99%

“…The youngest reported case of bradycardia after RDV administration was identified within this study. In a 3-month-old infant, SB was recorded after the third dose of RDV when the infant’s HR dropped to 80 bpm from 130 bpm at baseline and resolved after discontinuation of the drug [ 23 ]. To further explore the effect of RDV on arrhythmia and quantify reduction in HR, an Italian case series of 52 patients who underwent daily electrocardiogram (ECG) found a mean HR reduction of 24 ± 16 bpm, which was greater among men than women (28 ± 16 bpm vs. 18 ± 14 bpm, P < 0.05) [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, RDV showed a temporal association with a complete atrioventricular (AV) block in a case of a 72-yearold male with a history of atrial fibrillation and lung cancer [19]. Within 24 h of RDV administration, the patient was noted to be in atrial fibrillation with ventricular rates of 30 -40 bpm, which progressed to complete AV block on day 5 of RDV therapy and spontaneously resolution within 48 h. Three case series exploring the association between bradyarrhythmia after administration of RDV to SARS-CoV-2-infected patients were also identified in the literature [22][23][24]. In a case series from Poland investigating 19 hospitalized patients with marked self-limiting SB, 12 were treated with RDV before the appearance of SB (usually on day 1 or 2 of therapy) [22].…”

Section: Narrative Review Of Literaturementioning

confidence: 99%

“…However, in a later retrospective study by the same authors, the frequency of bradycardia after RDV was found to be 16.8% in a cohort of 473 patients hospitalized with COV-ID-19 [27]. Characteristics of these observational studies and case series can be found in Table 3 [22][23][24][25][26][27].…”

Section: Narrative Review Of Literaturementioning

confidence: 99%

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Bradyarrhythmia After Remdesivir Administration in SARS-CoV-2: A Review of Literature and Meta-Analysis of Observational Studies in Epidemiology

et al. 2022

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Background The coronavirus disease 2019 (COVID-19) pandemic has required timely and informed decisions about treatment recommendations for clinical practice. One such drug used for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is remdesivir (RDV), and several cardiac side effects have been reported including bradyarrhythmia (e.g., transient sinus bradycardia, symptomatic sinus bradycardia, complete atrioventricular (AV) block). The current study aimed to explore the association between RDV treatment for SARS-CoV-2 infection and the risk of bradyarrhythmia by presenting a review and meta-analysis of available published studies. Methods We presented a review of published literature and meta-analysis of observational studies (MOOSE). A narrative summary of RDV and bradyarrhythmia in COVID-19 infection and pooled analysis of observational studies that meet inclusion criteria was included. Studies included were published between January 2020 and December 2021 (identified through PubMed and ScienceDirect) and examined the association between treatment with RDV in SARS-CoV-2 infection and the risk of bradyarrhythmia. Results Three studies (two retrospective cohort studies and one prospective cohort study) met inclusion criteria for pooled meta-analysis of bradyarrhythmia and RDV therapy in COVID-19 patients. Treatment with RDV was associated with increased risk of sinus bradycardia when compared to controls (odds ratio 3.27 (95% confidence interval 1.90 - 5.63)). In the pooled analysis, the incidence of bradycardia in those that received RDV was 34.07% vs. 18.13% among controls. Thirteen case reports, three case series, and three disproportionality analyses were identified in review of the literature. Conclusion Data from real-world observational studies suggest that treating COVID-19 patients with RDV may predispose the development of bradyarrhythmia. The importance of this observation is of uncertain clinical significance as some observational studies have reported more favorable outcomes among patients who experience bradycardia after RDV therapy. The current study is limited by the small number of studies that could be meaningfully pooled and more well-designed cohort studies are needed to explore this association.

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Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project

et al. 2023

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ImportanceThe rapid spread and mortality associated with COVID-19 emphasized a need for surveillance system development to identify adverse events (AEs) to emerging therapeutics. Bradycardia is a remdesivir infusion–associated AE listed in the US Food and Drug Administration–approved prescribing information.ObjectiveTo evaluate the magnitude and duration of bradycardic events following remdesivir administration.Design, Setting, and ParticipantsA multicenter cohort study of patients with recorded heart rate less than 60 beats per minute within 24 hours after administration of a remdesivir dose was conducted between November 23, 2020, and October 31, 2021. Participants included patients hospitalized with COVID-19 at 15 medical centers across the US. Patients excluded had AEs unrelated to bradycardia, AEs in addition to bradycardia, or first onset of bradycardia after 5 remdesivir doses.ExposuresRemdesivir administration.Main Outcomes and MeasuresLinear mixed-effect models for the minimum HR before starting remdesivir and within 24 hours of each dose included doses as fixed effects. Baseline covariates were age (≥65 years vs &lt;65 years), sex (male vs female), cardiovascular disease history (yes vs no), and concomitant use of bradycardia-associated medications. The interactions between variables and doses were considered fixed-effects covariates to adjust models.ResultsA total of 188 patients were included in the primary analysis and 181 in the secondary analysis. The cohort included 108 men (57.4%); 75 individuals (39.9%) were non-Hispanic White and mean (SD) age was 61.3 (15.4) years. Minimum HR after doses 1 to 5 was lower than before remdesivir. Mean minimum HR was lowest after dose 4, decreasing by −15.2 beats per minute (95% CI, −17.4 to −13.1; P &lt; .001) compared with before remdesivir administration. Mean (SD) minimum HR was 55.6 (10.2) beats per minute across all 5 doses. Of 181 patients included in time-to-event analysis, 91 had their first episode of bradycardia within 23.4 hours (95% CI, 20.1-31.5 hours) and 91 had their lowest HR within 60.7 hours (95% CI, 54.0-68.3 hours). Median time to first bradycardia after starting remdesivir was shorter for patients aged 65 years or older vs those younger than 65 years (18.7 hours; 95% CI, 16.8-23.7 hours vs 31.5 hours; 95% CI, 22.7-39.3 hours; P = .04). Median time to lowest HR was shorter for men vs women (54.2 hours; 95% CI, 47.3-62.0 hours vs 71.0 hours; 95% CI, 59.5-79.6 hours; P = .02).Conclusions and RelevanceIn this cohort study, bradycardia occurred during remdesivir infusion and persisted. Given the widespread use of remdesivir, practitioners should be aware of this safety signal.

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Sinus Bradycardia in Children Treated With Remdesivir for COVID-19

Cited by 13 publications

References 4 publications

Therapeutic Management of COVID-19 in a Pediatric Patient with Neurodegenerative CLN2 Disease and ICV—Enzyme Replacement Therapy: A Case Report

Therapeutic Management of COVID-19 in a Pediatric Patient with Neurodegenerative CLN2 Disease and ICV—Enzyme Replacement Therapy: A Case Report

Bradyarrhythmia After Remdesivir Administration in SARS-CoV-2: A Review of Literature and Meta-Analysis of Observational Studies in Epidemiology

Identification of Bradycardia Following Remdesivir Administration Through the US Food and Drug Administration American College of Medical Toxicology COVID-19 Toxic Pharmacovigilance Project

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