Although coronavirus disease 2019 (COVID-19) is commonly mild with the majority of children requiring only supportive care as the primary management strategy, for children who develop severe or critical disease, decision-making regarding antiviral therapy should weigh individual risks and benefits, informed by available evidence, according to a guidance statement published in the Journal of the Pediatric Infectious Diseases Society.
Developed by a panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions, and endorsed by the Pediatric Infectious Diseases Society, the guidance statement reflects evidence as of April 14, 2020, at which time no agent had been identified with proven efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As such, the guideline authors noted that as evidence evolves rapidly, there would be need for updates to the guidance. They stressed that clinicians should incorporate emerging evidence to inform current and future treatment decision as well as refer to the guidelines published by the Infectious Diseases Society of America.
Given the unknown efficacy of proposed antivirals for treating COVID-19, the key guiding principle when considering the use of these agents for children should be to first do no harm. Although a substantial majority of all children with COVID-19 will only need supportive care, among children with severe or critical COVID-19, antivirals may be considered on a case-by-case basis, preferably as part of a clinical trial, if available. Moreover, the use of antivirals should be restricted to children with positive virologic testing for COVID-19 to avoid exposure to unnecessary harms of antiviral treatment.
In the absence of clinical trial availability, antivirals should be offered with appropriate monitoring and in consultation with a pediatric infectious disease specialist, whenever possible. Mild or moderate COVID-19 should be managed with supportive care only, without antiviral agents, in outpatients and hospitalized patients. In addition, the panel suggested “that clinical criteria, and specifically respiratory support requirements, be used to define scenarios in which use of antiviral agents is considered” because the risks for unproven therapy are most tolerable among patients in critical condition due to the infection.
The panel noted that there are no definitive data to support any specific risk factors for severe COVID-19 in children. Further, there is insufficient evidence that the following are a risk factor in the pediatric population: young age, obesity without considering comorbidities, type 1 or 2 diabetes alone without associated comorbidities, mild/moderate immunocompromise, severe immunocompromise, severe underlying cardiac disease, and severe underlying pulmonary disease. Based on adult studies of patients with COVID-19 and extrapolation from other viral infections, children with severe immunocompromise, severe underlying cardiac disease, and those with severe underlying pulmonary disease may be more likely to experience severe illness.
If an antiviral is used, the panel suggested the use of remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available, with a dosing regimen that includes a loading dose on day 1 and a total duration of no more than 5 days, because this regimen has the advantage of substantial clinical experience and a track record of safety. In cases where there is a known glucose-6-phosphate-dehydrogenase deficiency for hemolysis, the panel suggested monitoring patients during hydroxychloroquine therapy.
The panel was divided as to whether lopinavir-ritonavir could or should be considered for any pediatric patient with COVID-19 infection in any clinical scenario. “As of April 14, 2020, there are no US-based clinical trials registered on clinicaltrials.gov evaluating lopinavir-ritonavir for the treatment of COVID-19, though there are multiple ongoing and planned trials in other countries,” added the guideline authors.
The panel recommended against use of hydroxychloroquine in combination with azithromycin. In addition, they recommended against combination therapy with lopinavir-ritonavir and ribavirin.
The guideline authors stressed that since there are no antivirals with proven efficacy for the treatment of COVID-19 as of April 14, 2020, clinicians should comply with local institutional and regulatory policies for experimental therapies if given outside of a clinical trial.
Chiotos K, Hayes M, Kimberlin DW, et al. Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2 [published online April 22, 2020]. J Pediatric Infect Dis Soc. doi:10.1093/jpids/piaa045