Use of Monoclonal Antibody to Treat COVID-19 in Children and Adolescents: Risk of Abuse of Prescription and Exacerbation of Health Inequalities

Abstract

Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 in infected patients are a new class of antiviral agents approved as a type of passive immunotherapy. They should be administered to adults and children (≥12 years old, weighing ≥ 40 kg) with SARS-CoV-2 positivity, and who are suffering from a chronic underlying disease and are at risk of severe COVID-19 and/or hospitalization. The aim of this manuscript is to discuss the benefit-to-risk of mAb therapy to treat COVID-19 in pediatric age, according to current reports. A problem is that the authorization for mAbs use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly reduced than in adults and the role of chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined. In addition, criteria presently suggested for use of mAbs in children and adolescents are very broad and may cause individual clinicians or institutions to recommend these agents on a case-by-case basis, with an abuse in mAbs prescriptions and an exacerbation of health inequalities while resources are scarce. Several questions need to be addressed before their routine use in clinical practice, including what is their associated benefit-to-risk ratio in children and adolescents, who are the patients that could really have benefit from their use, and if there is any interference of mAb therapy on recommended vaccines. While we wait for answers to these questions from well-conducted research, an effective and safe COVID-19 vaccine for vulnerable pediatric patients remains the best strategy to prevent COVID-19 and represents the priority for public health policies.

A COVID-19 primer for primary care clinicians

“…Though small numbers of pediatric and adolescent participants were included in the BLAZE-1 trial (which evaluated the safety and efficacy of the mAb cocktail bamlanivimab and etesevimab), 60 , 61 and even though phase III of the casirivimab and imdevimab trial assessing efficacy in those 12-17 years of age is currently ongoing, 62 , 63 the impetus for closely studying these drugs in the pediatric population has been low because of the overall greater risk of severe COVID-19 disease in the adult population. 64 Whether the increased frequencies of pediatric hospitalizations and severe illness in children resulting from Delta or future variants spur greater investigation into more widespread use of these agents for children and adolescents remains to be seen. Until such time, decisions regarding when eligible pediatric patients should receive mAbs will be primarily based on the discretion of the treating clinician.…”

COVID-19 in Children: Update on Diagnosis and Management

“…Monoclonal antibodies (mAbs; bamlanivimab plus etesevimab or casirivimab plus imdevimab) should be used with extreme caution on a case-by-case basis to avoid an abuse in prescriptions and an exacerbation of health inequalities while resources are scarce. 70 Although studies evaluating the efficacy, safety, and tolerability of mAbs in pediatric patients are limited, mAbs have been authorized for children (≥12 years old, weighing ≥40 kg) with SARS-CoV-2 positivity when they suffer from a chronic underlying disease at risk of severe COVID-19 and/or hospitalization. However, the identification of these patients is difficult as the risk of severe COVID-19 in pediatric age is significantly lower than in adults, 71 and the role of chronic underlying disease as a risk factor of severe COVID-19 in pediatric patients has not been precisely defined.…”

Eligibility criteria for pediatric patients who may benefit from anti SARS-CoV-2 monoclonal antibody therapy administration: an Italian inter-society consensus statement

“…In addition, infected pediatric patients have often showed a favorable outcome regardless of the presence of risk factors or comorbidities [ 8 ]. For these reasons, their utilization is still under debate [ 9 ] calling for a judicious and detailed use.…”