Compassionate use of remdesivir boosts recovery of children with severe COVID-19

Most children with severe COVID-19 appear to fare well with remdesivir treatment, which leads to a high rate of clinical recovery with a favourable tolerability profile, as shown in a recent study.

In a cohort of 77 hospitalized children (median age 14 years) with confirmed SARS-CoV-2 infection, compassionate use of remdesivir resulted in a decreased oxygen-support requirement for 88 percent, recovery for 83 percent, and discharge for 73 percent by day 28 of follow-up. [Pediatrics 2021;doi:10.1542/peds.2020-047803]

The numbers were consistent in the subgroup of children requiring invasive ventilation at baseline. Specifically, 90 percent were extubated, 80 percent recovered, and 67 percent were discharged.

“Children who required invasive respiratory support at baseline were less likely to recover and recovered more slowly, but nevertheless, nearly 80 percent had recovered by day 28, demonstrating that good clinical outcomes can be achieved even in those with severe presentations,” according to the investigators.

Remdesivir was well tolerated, and the incidence of serious adverse events (AEs) was low at 16 percent. Most AEs were related to COVID-19 or comorbid conditions. Laboratory abnormalities, including elevations in transaminase levels, were common; the majority (61 percent) were grades 1 or 2.

There were four deaths recorded, and three of these were attributed to COVID-19.

“Although most children who become infected with SARS-CoV-2 experience mild or no symptoms and recover fully without medical care, a subset of paediatric patients develop life-threatening symptoms and require hospitalization,” the investigators noted.

Still, there are fewer deaths among children requiring admission to the intensive care unit than that reported in adults. “We believe these results represent an important contribution to understanding COVID-19 in paediatric patients and the safety and possible benefit of remdesivir in this population, they said.” [J Pediatr 2020;223:14-19.e]

The study cohort comprised 58 children in the US, seven in Spain, six in the UK, four in Italy, and one each in France and Germany. Seventy-nine percent of children had at least one comorbid condition. At baseline, 90 percent required supplemental oxygen and 51 percent needed invasive ventilation.

Remdesivir was administered intravenously, with the intended treatment course being 10 days. Children who weighed ≥40 kg received 200 mg on day 1 and 100 mg daily subsequently, whereas those weighing <40 kg were given 5 mg/kg on day 1 and 2.5 mg/kg daily subsequently.

The results require careful interpretation, as the study was not clinical but a compassionate-use programme undertaken to provide remdesivir to paediatric patients who were seriously ill, the investigators acknowledged.

“Without comparative data from a randomly assigned control group, it is not possible to say if the high level of recovery observed in these patients was due to the effects of remdesivir, the natural course of the disease, or other therapeutic interventions,” they added.

Currently, the safety, tolerability, pharmacokinetics, and efficacy of remdesivir in children are being assessed in phase II and III studies.