An Approach to the Treatment of Children With COVID-19

Boast, Alison; Curtis, Nigel; Holschier, Johanna; Purcell, Rachael; Bannister, Samantha; Plover, Christine; N, Maidhili Chinnappa; Burgner, David; Boyce, Suzanne; McNab, Sarah; Gwee, Amanda

doi:10.1097/inf.0000000000003576

Cited by 6 publications

(7 citation statements)

References 68 publications

(105 reference statements)

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“…Thus, unlike in adults, it does not appear that children are being less severely affected by emerging variants, and understanding the clinical presentation of COVID-19 in children is needed to design therapeutic trials on this population. Moreover, as the pediatric COVID-19 clinical phenotype shift occurs over time, clinicians should remain alert to its possible presence, test when clinically indicated, and treat when appropriate (eg, corticosteroids in children hospitalized with COVID-19–associated pneumonia) …”

Section: Discussionmentioning

confidence: 99%

Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada

et al. 2023

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ImportanceClinical manifestations of SARS-CoV-2 variants have not been systematically compared in children.ObjectiveTo compare symptoms, emergency department (ED) chest radiography, treatments, and outcomes among children with different SARS-CoV-2 variants.Design, Setting, and ParticipantsThis multicenter cohort study was performed at 14 Canadian pediatric EDs. Participants included children and adolescents younger than 18 years (hereinafter referred to as children) tested for SARS-CoV-2 infection in an ED between August 4, 2020, and February 22, 2022, with 14 days of follow-up.Exposure(s)SARS-CoV-2 variants detected on a specimen collected from the nasopharynx, nares, or throat.Main Outcomes and MeasuresThe primary outcome was presence and number of presenting symptoms. The secondary outcomes were presence of core COVID-19 symptoms, chest radiography findings, treatments, and 14-day outcomes.ResultsAmong 7272 participants presenting to an ED, 1440 (19.8%) had test results positive for SARS-CoV-2 infection. Of these, 801 (55.6%) were boys, with a median age of 2.0 (IQR, 0.6-7.0) years. Children with the Alpha variant reported the fewest core COVID-19 symptoms (195 of 237 [82.3%]), which were most often reported by participants with Omicron variant infection (434 of 468 [92.7%]; difference, 10.5% [95% CI, 5.1%-15.9%]). In a multivariable model with the original type as the referent, the Omicron and Delta variants were associated with fever (odds ratios [ORs], 2.00 [95% CI, 1.43-2.80] and 1.93 [95% CI, 1.33-2.78], respectively) and cough (ORs, 1.42 [95% CI, 1.06-1.91] and 1.57 [95% CI, 1.13-2.17], respectively). Upper respiratory tract symptoms were associated with Delta infection (OR, 1.96 [95% CI, 1.38-2.79]); lower respiratory tract and systemic symptoms were associated with Omicron variant infection (ORs, 1.42 [95% CI, 1.04-1.92] and 1.77 [95% CI, 1.24-2.52], respectively). Children with Omicron infection most often had chest radiography performed and received treatments; compared with those who had Delta infection, they were more likely to have chest radiography performed (difference, 9.7% [95% CI, 4.7%-14.8%]), to receive intravenous fluids (difference, 5.6% [95% CI, 1.0%-10.2%]) and corticosteroids (difference, 7.9% [95% CI, 3.2%-12.7%]), and to have an ED revisit (difference, 8.8% [95% CI, 3.5%-14.1%]). The proportions of children admitted to the hospital and intensive care unit did not differ between variants.Conclusions and RelevanceThe findings of this cohort study of SARS-CoV-2 variants suggest that the Omicron and Delta variants were more strongly associated with fever and cough than the original-type virus and the Alpha variant. Children with Omicron variant infection were more likely to report lower respiratory tract symptoms and systemic manifestations, undergo chest radiography, and receive interventions. No differences were found in undesirable outcomes (ie, hospitalization, intensive care unit admission) across variants.

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Section: Discussionmentioning

confidence: 99%

Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada

et al. 2023

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“…Doses for COVID-19-specific treatment are derived from studies in the adult population, sometimes also including adolescents, but seldom in individuals younger than 12 years and weighing less than 40 kg. Indeed, randomized controlled trials (RCTs) have not systematically included the pediatric population so far, with scarce evidence on efficacy, safety, and optimal doses [ 4 , 7 , 14 ]. Moreover, ethical concerns have risen around the construction of RCTs for COVID-19 antivirals and MAbs in children, arguing about the possibly unethical nature of trials, as severe presentations are rare [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence of compassionate use of remdesivir in children with severe and non-severe COVID-19, especially with underlying complex medical conditions and/or infants, with clinical benefit and a good safety profile, similarly to what emerged from our results [ 8 , 17 ]. Remdesivir is recommended intravenously for 3–5 days for children with a positive SARS-CoV-2 PCR test dating back to the previous 3–4 days [ 7 ]. In our study, the currently available indications were followed for its use on our population.…”

Section: Discussionmentioning

confidence: 99%

“…It is an inhibitor of cytochrome (CYP) P450 3A, to be considered in the case of polytherapy regimens, with other drugs that may induce or be metabolized by the same pathway, for risk of lower drug concentrations and a lesser response. EPIC-HR RCT in its phases 2 and 3 is underway on a population of patients of ages between 6 and 17 years [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the early stage of the pandemic, children have not been included in the clinical trials for COVID-19 treatment development, with consequently limited evidence in this age group. For this reason, many of these drugs, such as antivirals and monoclonal antibodies (MAbs), are used off-label in children, especially those under 12 years of age and weighing less than 40 kg ( , accessed on 1 September 2022) [ 7 , 8 ]. Moreover, fragile children, such as immunosuppressed patients, transplant recipients, or with onco-hematological, pulmonary, or cardiac comorbidities, might benefit from early treatment as soon as SARS-CoV-2 positivity is discovered through nasopharyngeal swab, even in the absence of symptoms.…”

Section: Introductionmentioning

confidence: 99%

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Early Treatments of Fragile Children with COVID-19—Results of CLEVER (Children COVID Early Treatment), a Retrospective, Observational Study

Minotti

Mengato

Pieri

et al. 2023

Viruses

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(1) Background: SARS-CoV-2 infection is notably mild in children, though comorbidities may increase the risk of hospitalization and may represent a risk for increased disease severity. There is an urgent need for targeted therapies with an acceptable efficacy and safety profile. To date, most of the medicines for COVID-19-specific treatment are prescribed off-label for children due to a lack of clinical trials and consequent evidence in this population. (2) Methods: This was a retrospective, observational study investigating the safety of treatments for the prevention of severe COVID-19 in fragile pediatric patients who received monoclonal antibodies and antivirals for mild-to-moderate symptoms between December 2021 and July 2022. (3) Results: Thirty-two patients were included. Monoclonal antibodies were prescribed to 62%, intravenous antivirals to 22%, and oral antivirals to 16% of children. Sotrovimab was the most frequently prescribed drug among monoclonal antibodies and overall (59%). The second most prescribed drug was remdesivir (22%). No severe adverse drug reaction was reported. There was no progression to severe disease and no death cases due to COVID-19 or drug administration. At drug-type stratification, resolution of symptoms and swab positivity time showed no difference between the two groups at 7 and 28 days. Off-label prescriptions were 84% overall, and in similar proportions between the two groups. (4) Conclusions: in this small sample, antivirals seemed safe and showed no differences in efficacy as compared to MAbs for the early treatment of COVID-19 in fragile children, thus representing a valuable choice, even when administered off-label.

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COVID-19 and MIS-C treatment in children—results from an international survey

Donà,

Minotti,

Masini

et al. 2023

Eur J Pediatr

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Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. In addition, access to COVID-19 therapeutics remains limited. Collecting physicians’ experiences with off-label use of therapeutics is important to inform global prioritization processes and better target pediatric research and development. A standardized questionnaire was designed to explore the use of therapeutics used to treat COVID-19 and multisystem inflammatory syndrome in children (MIS-C) in pediatric patients globally. Seventy-three physicians from 29 countries participated. For COVID-19, steroids were used by 75.6% of respondents; remdesivir and monoclonal antibodies were prescribed by 48.6% and 27.1% of respondents, respectively. For MIS-C, steroids were prescribed by 79.1% of respondents and intravenous immunoglobulins by 69.6%. The use of these products depended on their pediatric approval and the limited availability of antivirals and most monoclonal antibodies in Africa, South America, Southeast Asia, and Eastern Europe. Off-label prescription resulted widespread due to the paucity of clinical trials in young children at the time of the survey; though, based on our survey results, it was generally safe and led to clinical benefits. Conclusion: This survey provides a snapshot of current practice for treating pediatric COVID-19 worldwide, informing global prioritization efforts to better target pediatric research and development for COVID-19 therapeutics. Off-label use of such medicines is widespread for the paucity of clinical trials under 12 years and 40 kg, though appears to be safe and generally results in clinical benefits, even in young children. However, access to care, including medicine availability, differs widely globally. Clinical development of COVID-19 antivirals and monoclonal antibodies requires acceleration to ensure pediatric indication and allow worldwide availability of therapeutics that will enable more equitable access to COVID-19 treatment. What is Known:• Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication.• Access to care differs widely globally, so because of the diversity of national healthcare systems; the unequal availability of medicines for COVID-19 treatment represents an obstacle to the pediatric population's universal right to health care. What is New:• Off-label COVID-19 drug prescription is widespread due to the lack of clinical trials in children younger than 12 years and weighing less than 40 kg, but relatively safe and generally leading to clinical benefit.• The application of the GAP-f framework to COVID-19 medicines is crucial, ensuring widespread access to all safe and effective drugs, enabling the rapid development of age-appropriate formulations, and developing specific access plans (including stability, storage, packaging, and labeling) for distribution in low- and middle-income countries (LMICs). Antivirals and monoclonal antibodies may benefit from the acceleration to reach widespread and equal diffusion.

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An Approach to the Treatment of Children With COVID-19

Cited by 6 publications

References 68 publications

Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada

Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada

Early Treatments of Fragile Children with COVID-19—Results of CLEVER (Children COVID Early Treatment), a Retrospective, Observational Study

COVID-19 and MIS-C treatment in children—results from an international survey

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