To the Editor:
Remdesivir (RDV) is approved by the Food and Drug Administration for hospitalized patients ≥12 years of age and weighing ≥40 kg. It is also available through the Food and Drug Administration Emergency Use Authorization for the treatment of hospitalized pediatric patients <12 years of age weighing 3.5–40 kg. Experts’ panels recommend the use of RDV primarily in children with “severe COVID-19” defined as new or increased requirements of supplemental oxygen compared with the baseline. However, comparative data on efficacy and safety of RDV in children are pending.1
Since November 2020, 4 children with COVID-19 pneumonia were treated with ampicillin, RDV and dexamethasone in the PID unit of our hospital. Three of them were female (3/4, 75%) and their median age was 11.5 years (range: 91 days–15.3 years). Their previous medical history was unremarkable. All patients presented with fever, dyspnea and low oxygen saturation requiring oxygen support, while chest radiographs revealed diffuse pulmonary infiltrates. Laboratory results were significant only for lymphopenia. Three of 4 children developed asymptomatic sinus bradycardia. At first, the heart rate of an adolescent 13.5 years of age dropped to 50 bpm after the fourth dose of RDV from 80 bpm at baseline. The second patient was a 10-year-old girl with a heart rate of 60 bpm after the third dose of the drug compared to 80 bpm at baseline. In the third case, asymptomatic sinus bradycardia was recorded in a 3-month-old infant whose heart rate dropped to 80 bpm after the third dose from 130 at baseline. Cardiological evaluation of all 3 patients was normal. Nonetheless, RDV was discontinued in the infant, while the 2 older children completed a 5-day treatment. Heart rate returned to normal within 24 hours after RDV discontinuation in the infant or after treatment completion in the older children. In all 3 patients, the clinical course was uncomplicated and they were discharged after a median of 5 days (range 4–7).
Remdesivir is recommended for the treatment of “severe COVID-19” in hospitalized children based on a randomized trial that demonstrated a shorter time to clinical recovery in hospitalized adults under treatment, with the greatest benefit found in those requiring supplemental oxygen without need for mechanical ventilation.2 Only few case reports regarding possible adverse effects of RDV on cardiovascular system exist in adults3; an adolescent with sinus bradycardia was recently reported by Sanchez-Codez et al.4 In a pharmacovigilance study, 11.6% of the reports concerning RDV were registered as cardiac effects and almost one-third of the latter were about bradycardia5; their median age was 61.2 (43.1–79.3) years old.
In agreement with previous reports, our findings suggest that awareness for possible adverse events and close monitoring of patients treated with RDV are required to ensure safe use, given that COVID-19 itself may cause severe cardiovascular complications. In both adults and children, continuous ECG monitoring may be beneficial for patients with underlying cardiac disorders that are considered at risk for severe COVID-19 or patients with compassionate treatments while waiting for control-randomized trials’ results.
1. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at: https://www.covid19treatmentguidelines.nih.gov/
. Accessed March 5, 2021
2. Beigel JH, Tomashek KM, Dodd LE.Remdesivir for the treatment of Covid-19 - preliminary report. Reply N Engl J Med. 2020;383:1813–1826
3. Gubitosa JC, Kakar P, Gerula C, et al. Marked sinus bradycardia associated with remdesivir in COVID-19: a case and literature review JACC Case Rep. 2020;18:2260–2264
4. Sanchez-Codez MI, Rodriguez-Gonzalez M, Gutierrez-Rosa I.Severe sinus bradycardia associated with Remdesivir in a child with severe SARS-CoV-2 infection Eur J Pediatr. 2021;23:1
5. Touafchia A, Bagheri H, Carrié D, et al. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns Clin Microbiol Infect. 2021;26:S1198-743X(21)00094-X