Daniel E Dulek1, Robert C Fuhlbrigge2, Alison C Tribble3, James A Connelly4, Michele M Loi5, Hassan El Chebib6, Shanmuganathan Chandrakasan7, William R Otto8, Caroline Diorio9, Garrett Keim10, Kelly Walkovich11, Preeti Jaggi12, Jennifer E Girotto6,13, April Yarbrough14, Edward M Behrens15, Randy Q Cron16, Hamid Bassiri8. 1. Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 2. Section of Rheumatology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA. 3. Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA. 4. Division of Pediatric Hematology Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 5. Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA. 6. Division of Infectious Diseases and Immunology, Department of Pediatrics, Connecticut Children's, Hartford, Connecticut, USA. 7. Division of Pediatric Hematology Oncology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA. 8. Division of Infectious Diseases, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 9. Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 10. Division of Critical Care Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 11. Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA. 12. Division of Pediatric Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA. 13. University of Connecticut School of Pharmacy, Storrs, Connecticut, USA. 14. Department of Pharmacy, Children's of Alabama, Birmingham, Alabama, USA. 15. Division of Pediatric Rheumatology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 16. Division of Pediatric Rheumatology, Department of Pediatrics, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
Abstract
BACKGROUND: Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of severe acute respiratory syndrome coronavirus 2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C). METHODS: A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion. RESULTS: The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multiorgan involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized. CONCLUSIONS: Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials.
BACKGROUND: Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of severe acute respiratory syndrome coronavirus 2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C). METHODS: A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion. RESULTS: The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multiorgan involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized. CONCLUSIONS: Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials.
Authors: Biykem Bozkurt; Sandeep R Das; Daniel Addison; Aakriti Gupta; Hani Jneid; Sadiya S Khan; George Augustine Koromia; Prathit A Kulkarni; Kathleen LaPoint; Eldrin F Lewis; Erin D Michos; Pamela N Peterson; Mohit K Turagam; Tracy Y Wang; Clyde W Yancy Journal: J Am Coll Cardiol Date: 2022-06-23 Impact factor: 27.203
Authors: Biykem Bozkurt; Sandeep R Das; Daniel Addison; Aakriti Gupta; Hani Jneid; Sadiya S Khan; George Augustine Koromia; Prathit A Kulkarni; Kathleen LaPoint; Eldrin F Lewis; Erin D Michos; Pamela N Peterson; Mohit K Turagam; Tracy Y Wang; Clyde W Yancy Journal: Circ Cardiovasc Qual Outcomes Date: 2022-06-23
Authors: Arnaud G L'Huillier; Lara Danziger-Isakov; Abanti Chaudhuri; Michael Green; Marian G Michaels; Klara M Posfay-Barbe; Dimitri van der Linden; Anita Verma; Mignon McCulloch; Monica I Ardura Journal: Pediatr Transplant Date: 2021-03-10
Authors: Jennifer A Belsky; Brian P Tullius; Margaret G Lamb; Rouba Sayegh; Joseph R Stanek; Jeffery J Auletta Journal: J Infect Date: 2021-02-04 Impact factor: 6.072