QTc interval prolongation in patients infected with SARS-CoV-2 and treated with antiviral drugs

Introduction: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics. Patients and methods: Pediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h in treatment and after 72 h. Results: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March -July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs. 416.5 ms (29.4) (p = 0.716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms (IQR 48.7) (p = 0.062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients >= 500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented. Conclusions: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc >500 ms. (c) 2021 Published by Elsevier Espana, S.L.U. on behalf of Asociacion Espanola de Pediatria. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Automated summary

Pediatric patients with COVID-19 who received antiviral therapy experienced QTc interval prolongation after 72 hours, although no arrhythmic events were observed. Active monitoring of QTc is recommended when using hydroxychloroquine and antiviral drugs, and treatment should be discontinued if QTc exceeds 500 ms.