COVID-19 and MIS-C treatment in children—results from an international survey
Authors: Donà Daniele , Minotti Chiara , Masini Tiziana , Penazzato Martina , Van Der Zalm Marieke M. , Judd Ali , Giaquinto Carlo , Lallemant Marc ,   Survey Respondents Consortium, Bouts Antonia H. M. , McCollum Eric , Bamford Alasdair , Rojo Pablo , Tagarro Alfredo , P. Nanny Nan , Lopez Eduardo , Bianchini Sonia , Nicolini Giangiacomo , Volokha Alla , Pierantoni Luca , Bernardi Stefania , Giacomet Vania , Alemayehu Tinsae , Swasdichai Kanokkron , Castagnola Elio , Verwey Charl , Velikov Petar , Palma Paolo , Mir Fatima , Isaac Rhian , Jahnukainen Timo , Calvo Cristina , Schwerk Nicolaus , Omolokun Omotakin , Tamborino Agnese , Della Negra Marinella , Hooli Shubhada , Reubenson Gary , A. Mazimpaka , Dixit Devika , Abbas Qalab , Gray Taryn , Gonzalez Vicent Marta , Webb Kate , Damasy Grace , Riordan Andrew , Lopes Maria Francelina , Kanjanavanit Suparat , Welch Steven , Lo Vecchio Andrea , Garazzino Silvia , Payne Helen , Ruenglerdpong Suchada , Masjosthusmann Katja , Kohns Vasconcelos Malte , Burgner David , Meneghesso Davide , Meneghel Alessandra , Whittaker Elizabeth , Aluoch Joseph , Thirapattarapong Vannee , Marczyńska Magdalena Maria , August Winnie , Rabie Helena , Groll Andreas , Castelli Gattinara Guido , Madrid Alvaro , Hierro Marial , Debray Dominique , Jamal Shelina , Calore Elisabetta , Cananzi Mara , De Pieri Marica , Brizuela Martin Eduardo , Kachikoti Chawanzi , Akabwai George , Seged Selam , Wolfs Tom , Karatzios Christos , Tovar Marco A. , A. Polynary , Kabeja Edward 
Published: September 2023

AbstractChildren 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.