key: cord-0807402-vdvjys4b
authors: Vora, S. B.; Englund, J. A.; Trehan, I.; Waghmare, A.; Kong, A.; Adler, A.; Zerr, D. M.
title: Monoclonal antibody and antiviral therapy for treatment of mild-to-moderate COVID-19 in pediatric patients
date: 2022-03-18
journal: nan
DOI: 10.1101/2022.03.16.22272511
sha: a69e2906cab0542aeb1b4a390427ed43e5323ab3
doc_id: 807402
cord_uid: vdvjys4b

The recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options for mild-to-moderate Covid-19 in high-risk adolescents and adults. In this report we describe patient characteristics, treatment-related process measures and outcomes associated with early Covid-19 therapy in high-risk pediatric patients.

The recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options for mild-to-moderate Covid-19 in high-risk adolescents and adults. Though the oral antiviral nirmatrelvir/ritonavir and the monoclonal antibody sotrovimab [1] were approved under Emergency Use Authorization (EUA) for children over 12 years of age, the studies leading up to this approval did not include any pediatric patients [2, 3] . A recent publication demonstrated a three-day course of remdesivir reduces hospitalization rates in high-risk outpatients including younger children [4] , but data around the use of any of these agents in children is extremely limited.

Based on Food and Drug Administration (FDA) EUA, pediatric-specific guidance [5] , and national prioritization schema [6] , our institution has prioritized monoclonal antibodies and early antivirals for severely immunocompromised and incompletely vaccinated patients with additional risk factors including severe obesity, medical complexity with respiratory technology dependence, or multiple other risk factors. Almost all SARS-CoV-2 strains were Omicron variant in our region by late December, 2021 [7] . In this report we describe patient characteristics, treatment-related process measures and outcomes associated with early Covid-19 therapy in high-risk pediatric patients.

Patients for whom Covid-19 treatment was requested between 12/22/2021-1/30/2022 were reviewed by our hospital's Covid-19 Therapeutics Committee with Pediatric Infectious Diseases, Emergency Medicine, and Pharmacy expertise. To determine which treatment to offer we considered each patient's age, location, ability to tolerate oral treatment, potential drug All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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interactions, underlying renal and liver function and current infusion center or inpatient bed availability. Following IRB approval, medical records were reviewed to assess patient demographics, underlying conditions, SARS-CoV-2 vaccination status, days since first symptom or positive test (PCR or rapid antigen), medication adherence, treatment associated adverse events, and Emergency Department (ED) visits and hospitalizations within 7 days after request intake. Assessment of baseline renal and hepatic function was recommended prior to remdesivir administration.

Requests for early treatment for 94 patients were reviewed; 66 (70%) received approval for sotrovimab, nirmatrelvir/ritonavir, or remdesivir (Table 1) . Immunocompromised patients comprised most requests (66%), with malignancy being the most frequent immunocompromising condition. The most common reasons for denial of therapy were fully vaccinated status and not being considered in the highest risk categories. Self-identified race and ethnicity categorizations were generally similar between those for whom therapy was requested versus approved. Therapy was not given despite approval to 19 patients, most often due to family refusal and improving symptoms ( Table 2) . Remdesivir treatment occurred most frequently in the inpatient setting while sotrovimab was administered more often in the outpatient infusion center. Adverse events were rare following all agents; no patients had a rise in alanine aminotransferase or creatinine after remdesivir. There were three new (not treatment related) hospitalizations in the follow-up period for potentially Covid-19 related disease, including one who did was not approved for treatment, one who was approved for sotrovimab but did not receive it, and one after treatment with remdesivir (see Table 2 for details). Two additional patients had ED visits, both after All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 18, 2022. ; https://doi.org/10.1101/2022.03.16.22272511 doi: medRxiv preprint therapy (1 sotrovimab, 1 nirmatrelvir/ritonavir); one patient each with shortness of breath and chest pain. Both were discharged in good condition.

This represents one of the first reports of early treatment of Covid-19 in high-risk children and adolescents infected with the Omicron variant of SARS-CoV-2. To the extent we can determine, all therapies were well tolerated and subsequent Covid-19 related ED visits or hospitalizations were uncommon.

While most children with Covid-19 do well without therapy, treatment of mild-to-moderate infection should be considered in those at highest risk of progression to severe disease. In fact, recent data demonstrates that hospitalization rates in children 0-4 increased significantly during

Omicron data predominance, therefore information around early treatment in pediatric patients has become even more important [8] . However, despite FDA EUA for sotrovimab and nirmatrelvir/ritonavir in patients over 12 years and remdesivir in children < 12 years, safety and efficacy data for these agents in pediatric patients is extremely limited. The early treatment of remdesivir study included only 8 patients < 18 years of age [4] .

Limitations of this study include its observational nature, small sample size at a single center, short follow up period and the possibility that not all adverse events and outcomes were reported in the medical record. As symptomatic patients with severe underlying conditions were more likely to have therapies requested and approved, true assessment of treatment impact on outcomes on a broader population is not possible. Though we saw no clear indicator of disparities in our approval process, we are doing further work to explore potential equity issues as have been seen in the distribution of Covid-19 therapies for adult populations nationwide [9] . All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 18, 2022. ; https://doi.org/10.1101/2022.03.16.22272511 doi: medRxiv preprint

COVID-19 Therapeutics for Nonhospitalized Patients

Oral Nirmaltrevir for High-Risk Nonhospitalized Adults with Covid-19

Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients

Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents

Online ahead of print

Treatment Guidelines Panel's Interim Statement on Patient Prioritization for Outpatient Anti-SARS-CoV-2 Therapies or Preventive Strategies When There Are Logistical or Supply Constraints. National Institutes of Health COVID 19 Treatment Guidelines

UW Virology COVID-19 Dashboard

Hospitalization of Infants and Children Aged 0-4 Years with Laboratory-Confirmed COVID-19-COVID-NET, 14 states

All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder

n/a n/a n/a n/a N=27 16 (59) 7 (26) 1 (4) 1 (4)

1** 0 0Emergency department visits*** 1** 1 Hospitalizations** 1 † 1 ‡ * Hospitalized after positive SARS-CoV-2 test for non-COVID-19 related reasons