Abstract Background Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population. Methods Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild COVID disease at Cincinnati Children’s Hospital Medical Center from 5/1/2020 through 3/1/2022 were identified retrospectively. In accordance with the FDA EUA, patients were eligible for monoclonal antibody administration if they were ≥12 years of age, weighed ≥40kg, and were at high risk of progressing to severe disease or hospitalization. Results Ninety-four patients received monoclonal antibody therapy, of which 14 (13.5%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (51.9%) received casirivimab-imdevimab, and 26 (25%) received sotrovimab. Ten patients (10.6%) experienced one or more adverse events. Of those, 2 (14.3%) received either bamlanivimab or bamlanivimab-etesivimab, 7 (12.9%) received casirivimab-imdevimab, and 1 (3.8%) received sotrovimab. Most common symptoms include rash, nausea, and throat irritation (table R1), the majority (90%) of which were mild, either self-resolving with infusion cessation (60%) or persistent but requiring no medical intervention (30%) (table R2). Of the patients who experienced adverse events, only 1 (10%) received medical intervention - epinephrine. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 15 patients (15.9%) required additional medical care for ongoing COVID symptoms (table R3). Eight (53.3%) of these were either hospitalized or received escalation of care while already in the hospital. Table R1. Infusion-related adverse events. Of note, several patients had more than one symptom. Table R2. Classification of adverse events by grade and monoclonal antibody. Grade I events are defined as mild and generally not bothersome. Grade II events are defined as moderate: bothersome, but not dangerous. Grade III events are defined as medically significant, but not immediately life-threatening, and often require medical intervention. Table R3. Patients who required additional medical care for ongoing COVID-19 symptoms within 90 days of receiving a monoclonal antibody. Conclusion Overall, monoclonal antibodies are safe, largely well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations. Disclosures Grant Schulert, MD, PhD, Novartis: Advisor/Consultant Paul Spearman, MD, CyanVac: Grant/Research Support|Meissa Vaccines: Grant/Research Support Grant C. Paulsen, MD, AstraZeneca: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lara A. Danziger-Isakov, MD, Ansun BioPharma: Contracted clinical research|Astellas: Contracted clinical research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted clinical research|Pfizer: Contracted clinical research|Takeda: Grant/Research Support|Takeda: Contracted clinical research|Viracor: Grant/Research Support.