TY - JOUR
T1 - COVID-19 and MIS-C treatment in children-results from an international survey
AU - Survey Respondents Consortium
AU - Donà, Daniele
AU - Minotti, Chiara
AU - Masini, Tiziana
AU - Penazzato, Martina
AU - Van Der Zalm, Marieke M
AU - Judd, Ali
AU - Giaquinto, Carlo
AU - Lallemant, Marc
AU - Bouts, A.H.M.
N1 - Funding Information: This work was supported by VERDI (SARS-CoV-2 variants Evaluation in pRegnancy and paeDIatrics cohorts, 101045989), funded by the European Union. This work was supported in part by the Medical Research Council (grant number MC_UU_00004/03). Funding Information: Open access funding provided by Università degli Studi di Padova within the CRUI-CARE Agreement. Funding Information: This work was supported by VERDI (SARS-CoV-2 variants Evaluation in pRegnancy and paeDIatrics cohorts, 101045989), funded by the European Union. This work was supported in part by the Medical Research Council (grant number MC_UU_00004/03). Antonia H. M. Bouts, Amsterdam institute for Infection and Immunity, Amsterdam University Medical Centers, Amsterdam, The Netherlands; Eric McCollum, JHpiego, Johns Hopkins School of Medicine, Lesotho; Alasdair Bamford, Great Ormond Street Hospital, London, UK; Pablo Rojo, Hospital Universitario 12 de Octubre, Madrid, Spain; Alfredo Tagarro, Hospital Universitario Infanta Sofía and Instituto de Investigación 12 de Octubre, Madrid, Spain; Nanny Nan P., Thailand; Eduardo Lopez, CEIP, Centro de Estudios en Infectología Pediátrica, Colombia, Sonia Bianchini, ASST Santi Paolo e Carlo, Milan, Italy; Giangiacomo Nicolini, Ospedale San Martino, ULSS1 Dolomiti, Belluno, Italy, Alla Volokha, Kyiv Children City Hospital 1, Kiev, Ukraine, Luca Pierantoni, RCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Stefania Bernardi, Bambino Gesù Children’s Hospital, Rome, Italy; Vania Giacomet, Sacco Hospital, Milan, Italy; Tinsae Alemayehu, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia; Kanokkron Swasdichai, Phrapokklao Hospital,Thailand; Elio Castagnola, IRCCS Istituto Giannina Gaslini, Genoa, Ital; Charl Verwey, University of the Witwatersrand, Johannesburg, South Africa; Petar Velikov, Medical University of Sofia, Sofia, Bulgaria; Paolo Palma, Bambino Gesù Children’s Hospital, Rome, Italy; Fatima Mir, The Aga Khan University, Karachi, Pakistan; Rhian Isaac, Birmingham Children’s Hospital, Birmingham, UK; Timo Jahnukainen, Helsingin Yliopisto, Helsinki, Finland; Cristina Calvo, Hospital Universitario La Paz, Madrid, Spain; Nicolaus Schwerk, Hannover Medical School, Hannover, Germany; Omotakin Omolokun, Cwm Taf NHS UHB, Wales, UK; Agnese Tamborino, IRCSS Meyer, Florence, Italy; Marinella Della Negra, Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil; Shubhada Hooli, Texas Children’s Hospital, USA; Gary Reubenson, Rahima Moosa Mother & Child Hospital, Johannesburg, South Africa; Mazimpaka A., Nyagatare DH, Rwanda; Devika Dixit, University of Calgary, Calgary, Canada; Qalab Abbas, The Aga Khan University, Karachi, Pakistan; Taryn Gray, Christiaan Barnard Memorial Hospital, Cape Town, South Africa; Marta Gonzalez Vicent, Hospital Niño Jesus, Madrid, Spain; Kate Webb, University of Cape Town, Cape Town, South Africa; Grace Damasy, Dodoma, Tanzania; Andrew Riordan, Alder Hey Children's Hospital, Liverpool, UK; Maria Francelina Lopes, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Suparat Kanjanavanit, Chipata Central Hospital, Chipata, Zambia, Steven Welch, University Hospitals Birmingham, Birmingham, UK; Andrea Lo Vecchio, University of Naples Federico II, Naples, Italy; Silvia Garazzino, Regina Margherita Children's Hospital, Infectious Diseases Unit, Turin, Italy; Helen Payne, St Mary’s Hospital, London, UK; Suchada Ruenglerdpong, Chiang Rai Prachanukroh, Chiang Rai, Thailand; Katja Masjosthusmann, University Hospital Muenster-General Pediatrics, Muenster, Germany; Malte Kohns Vasconcelos, UKBB, Basel, Switzerland; David Burgner, Royal Children's Hospital, Melbourne, Australia; Davide Meneghesso, Pediatric Nephrology Unit, Department of Women’s and Children’s Health, University of Padova, Via Giustiniani 3, 35128. Padova, Italy; Alessandra Meneghel, Pediatric Rheumatoogy Unit, Department of Women’s and Children’s Health, University of Padova, Via Giustiniani 3, 35128. Padova, Italy; Elizabeth Whittaker, Imperial College Healthcare NHS Trust, London, UK; Joseph Aluoch, Nairobi Hospital, Nairobi, Kenya; Vannee Thirapattarapong, Phayathai 3 Hospital, Bangkok, Thailand; Magdalena Maria Marczyńska, Department of Children's Infectious Diseases Medical University of Warsaw, Warsaw, Poland; Winnie August, Phayathai 3 Hospital, Bangkok, Thailand; Helena Rabie, Stellenbosch University, Stellenbosch, South Africa; Andreas Groll, Children's University Hospital Muenster, Muenster, Germany; Guido Castelli Gattinara, Bambino Gesù Children’s Hospital, Rome, Italy; Alvaro Madrid, Hospital Universitario Sant Joan de Deu Barcelona, Esplugues de Llobregat, Spain; Marial Hierro, Hospital Universitario La Paz, Madrid, Spain; Dominique Debray, Necker Enfants Malades-APHP, Paris, France; Shelina Jamal, Alberta Health Services, AHS, Alberta, Canada; Elisabetta Calore, Pediatric Oncohematology, Department of Women’s and Children’s Health, University of Padova, Via Giustiniani 3, 35128. Padova, Italy; Mara Cananzi, Pediatric Gastroenterology, Department of Women’s and Children’s Health, University of Padova, Via Giustiniani 3, 35128. Padova, Italy; Marica De Pieri, Division of Pediatric Infectious Diseases, Department of Women’s and Children’s Health, University of Padova, Via Giustiniani 3, 35128. Padova, Italy; Martin Eduardo Brizuela, Hospital Velez Sarsfield, Buenos Aires, Argentina; Chawanzi Kachikoti, Chipata Central Hospital, Chipata, Zambia; George Akabwai, Baylor, Uganda; Selam Seged, St Peters Specialised Hospital, Addis Ababa, Ethiopia; Tom Wolfs, Prinses Maxima Center for Pediatric Oncology, Utrecht, The Netherlands; Christos Karatzios, Montreal Children's Hospital, Montreal, Canada; Marco A. Tovar, Socios En Salud Sucursal, Lima, Peru; Polynary A., Kilosa District Hospital, Tanzania; Edward Kabeja, Tanzania. Publisher Copyright: © 2023, The Author(s).
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - Antivirals
KW - COVID-19
KW - Children
KW - Global access
KW - Monoclonal antibodies
KW - Off-label
UR - http://www.scopus.com/inward/record.url?scp=85170093951&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00431-023-05179-7
DO - https://doi.org/10.1007/s00431-023-05179-7
M3 - Article
C2 - 37672062
SN - 0340-6199
VL - 182
SP - 5087
EP - 5093
JO - European journal of pediatrics
JF - European journal of pediatrics
IS - 11
ER -