Remdesivir therapy causing bradycardia in COVID-19 patients: Two case reports

Abdelmajid, Alaaeldin; Osman, Wala; Musa, H H; Elhiday, Hisham; Munir, Waqar; Maslamani, Muna Al; Elmekaty, Eman

doi:10.1016/j.idcr.2021.e01254

Cited by 11 publications

(22 citation statements)

References 17 publications

(14 reference statements)

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“…The word cloud is dominated by ‘COVID-19’ (1324), ‘SARS-CoV-2’ (750), ‘remdesivir’ (326), ‘coronavirus’ (250), ‘molecular docking’ (94), ‘mortality’ (86), ‘hydroxychloroquine’ (65), ’pandemic’ (62), ‘treatment’ (57), and ‘antiviral’ (56), which suggests that these terms have the highest frequency in the literature on remdesivir. Another frequent keyword is ‘pneumonia,’ which is strongly associated with coronavirus [ 54 , 55 ]. This is why much research is conducted on the therapeutic efficacy of remdesivir.…”

Section: Resultsmentioning

confidence: 99%

Mapping Scientific Productivity Trends and Hotspots in Remdesivir Research Publications: A Bibliometric Study from 2016 to 2021

Ogunsakin

Ebenezer

Jordaan

et al. 2022

IJERPH

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In response to global efforts to control and exterminate infectious diseases, this study aims to provide insight into the productivity of remdesivir research and highlight future directions. To achieve this, there is a need to summarize and curate evidence from the literature. As a result, this study carried out comprehensive scientific research to detect trends in published articles related to remdesivir using a bibliometric analysis. Keywords associated with remdesivir were used to access pertinent published articles using the Scopus database. A total of 5321 research documents were retrieved, primarily as novel research articles (n = 2440; 46%). The number of publications increased exponentially from 2020 up to the present. The papers published by the top 12 institutions focusing on remdesivir accounted for 25.69% of the overall number of articles. The USA ranked as the most productive country, with 906 documents (37.1%), equivalent to one-third of the global publications in this field. The most productive institution was Icahn School of Medicine, Mount Sinai, in the USA (103 publications). The New England Journal of Medicine was the most cited, with an h-index of 13. The publication of research on remdesivir has gained momentum in the past year. The importance of remdesivir suggests that it needs continued research to help global health organizations detect areas requiring instant action to implement suitable measures. Furthermore, this study offers evolving hotspots and valuable insights into the scientific advances in this field and provides scaling-up analysis and evidence diffusion on remdesivir.

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Section: Resultsmentioning

confidence: 99%

Mapping Scientific Productivity Trends and Hotspots in Remdesivir Research Publications: A Bibliometric Study from 2016 to 2021

Ogunsakin

Ebenezer

Jordaan

et al. 2022

IJERPH

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show abstract

Section: Resultsmentioning

confidence: 99%

“…Table 2 presents the baseline demographics, diagnostic findings, and chief features of COVID‐19 patients who developed bradycardia from the individual cases compiled ( n = 59). 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 Bradycardia predominated in male patients ( n = 37) with a median age of 58.0 years old (IQR 48.0−71.0). Bradycardia was most often observed in patients classified as having severe or critical illness COVID‐19 (35.6% and 32.2%, respectively).…”

Section: Resultsmentioning

confidence: 99%

Characteristics of bradyarrhythmia in patients with COVID‐19: Systematic scoping review

Nagamine

Randhawa

Nishimura

et al. 2022

Pacing Clinical Electrophis

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COVID-19 has recently been associated with the development of bradyarrhythmias, although its mechanism is still unclear. We aim to summarize the existing evidence regarding bradyarrhythmia in COVID-19 and provide future directions for research.Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"Bradycardia," "atrioventricular block," and "COVID-19″ from their inception to October 13, 2021. Fortythree articles, including 11 observational studies and 59 cases from case reports and series, were included in the systematic review. Although some observational studies reported increased mortality in those with bradyarrhythmia and COVID-19, the lack of comparative groups and small sample sizes hinder the ability to draw definitive conclusions. Among 59 COVID-19 patients with bradycardia from case reports and series, bradycardia most often occurred in those with severe or critical COVID-19, and complete heart block occurred in the majority of cases despite preserved LVEF (55.9%).Pacemaker insertion was required in 76.3% of the patients, most of which were permanent implants (45.8%). This systematic review summarizes the current evidence and characteristics of bradyarrhythmia in patients with COVID-19. Further studies are critical to assess the reversibility of bradyarrhythmia in COVID-19 patients and to clarify potential therapeutic targets including the need for permanent pacing.

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“…With respect to current cardiac and kidney safety concerns due to remdesivir treatment (Abdelmajid et al 2021 ; Chouchana et al 2021 ; Gérard et al 2021 ; Pallotto et al 2021 ; Rafaniello et al 2021 ; Touafchia et al 2021 ), we here investigated the toxicity of remdesivir in cardiac and kidney cells and found adverse effects of remdesivir on cell proliferation, mitochondrial function, and the beating behavior of NMCM.…”

Section: Discussionmentioning

confidence: 99%

The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro

et al. 2022

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Remdesivir is a prodrug of a nucleoside analog and the first antiviral therapeutic approved for coronavirus disease. Recent cardiac safety concerns and reports on remdesivir-related acute kidney injury call for a better characterization of remdesivir toxicity and understanding of the underlying mechanisms. Here, we performed an in vitro toxicity assessment of remdesivir around clinically relevant concentrations (Cmax 9 µM) using H9c2 rat cardiomyoblasts, neonatal mouse cardiomyocytes (NMCM), rat NRK-52E and human RPTEC/TERT1 cells as cell models for the assessment of cardiotoxicity or nephrotoxicity, respectively. Due to the known potential of nucleoside analogs for the induction of mitochondrial toxicity, we assessed mitochondrial function in response to remdesivir treatment, early proteomic changes in NMCM and RPTEC/TERT1 cells and the contractile function of NMCM. Short-term treatments (24 h) of H9c2 and NRK-52E cells with remdesivir adversely affected cell viability by inhibition of proliferation as determined by significantly decreased 3H-thymidine uptake. Mitochondrial toxicity of remdesivir (1.6–3.1 µM) in cardiac cells was evident by a significant decrease in oxygen consumption, a collapse of mitochondrial membrane potential and an increase in lactate secretion after a 24–48-h treatment. This was supported by early proteomic changes of respiratory chain proteins and intermediate filaments that are typically involved in mitochondrial reorganization. Functionally, an impedance-based analysis showed that remdesivir (6.25 µM) affected the beat rate and contractility of NMCM. In conclusion, we identified adverse effects of remdesivir in cardiac and kidney cells at clinically relevant concentrations, suggesting a careful evaluation of therapeutic use in patients at risk for cardiovascular or kidney disease.

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Remdesivir therapy causing bradycardia in COVID-19 patients: Two case reports

Cited by 11 publications

References 17 publications

Mapping Scientific Productivity Trends and Hotspots in Remdesivir Research Publications: A Bibliometric Study from 2016 to 2021

Mapping Scientific Productivity Trends and Hotspots in Remdesivir Research Publications: A Bibliometric Study from 2016 to 2021

Characteristics of bradyarrhythmia in patients with COVID‐19: Systematic scoping review

The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro

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