Characterizing Long COVID in Children and Adolescents
Publication information:
Rachel Gross, Tanayott Thaweethai, Lawrence Kleinman, Jessica Snowden, Erika Rosenzweig, Joshua Milner, Kelan Tantisira, Kyung Rhee, Terry Jernigan, Patricia Kinser, Amy Salisbury, David Warburton, Sindhu Mohandas, John Wood, Jane Newburger, Dongngan Truong, Valerie Flaherman, Torri Metz, Elizabeth Karlson, Lori Chibnik, Deepti Pant, Aparna Krishnamoorthy, Richard Gallagher, Michelle Lamendola-Essel, Denise Hasson, Stuart Katz, Shonna Yin, Benard Dreyer, Megan Carmilani, Coombs, Megan Fitzgerald, Nick Güthe, Mady Hornig, Rebecca Letts, Aimee Peddie, Brittany Taylor, Venkataraman Balaraman, Amanda Bogie, Hulya Bukulmez, Allen Dozor, Daniel Eckrich, Amy Elliott, Danielle Evans, Jonathan Farkas, Vincent Faustino, Laura Fischer, Sunanda Gaur, Ashraf Harahsheh, Uzma Hasan, Daniel Hsia, Gredia Huerta-Montañez, Kathy Hummel, Matt Kadish, David Kaelber, Sankaran Krishnan, Jessica Kosut, Jerry Larrabee, Peter Paul Lim, Ian Michelow, Carlos Oliveira, Hengameh Raissy, Zaira Rosario-Pabon, Judith Ross, Alice Sato, Michelle Stevenson, Maria Talavera-Barber, Ronald Teufel, Kathryn Weakley, Emily Zimmerman, Marie-Abele Bind, James Chan, Zoe Guan, Richard Morse, Harrison Reeder, Natascha Akshoomoff, Judy Aschner, Rakesh Bhattacharjee, Lesley Cottrell, Kelly Cowan, Viren D’Sa, Alexander Fiks, Maria Gennaro, Katherine Irby, Manaswitha Khare, Jeremy Landeo Guttierrez, Russell McCulloh, Shalu Narang, Manette Ness-Cochinwala, Sheila Nolan, Paul Palumbo, Julie Ryu, Juan Salazar, Rangaraj Selvarangan, Cheryl Stein, Alan Werzberger, William Zempsky, Robin Aupperle, Fiona Baker, Marie Banich, Deanna Barch, Arielle Baskin-Sommers, James Bjork, Susan Bookheimer, Sandra Brown, Casey, Linda Chang, Duncan Clark, Anders Dale, Mirella Dapretto, Thomas Ernst, Damien Fair, Sarah Feldstein Ewing, John Foxe, Edward Freedman, Naomi Friedman, Hugh Garavan, Dylan Gee, Raul Gonzalez, Kevin Gray, Mary Heitzeg, Megan Herting, Joanna Jacobus, Angela Laird, Christine Larson, Krista Lisdahl, Monica Luciana, Beatriz Luna, Pamela Madden, Erin McGlade, Eva Müller-Oehring, Bonnie Nagel, Michael Neale, Martin Paulus, Alexandra Potter, Perry Renshaw, Elizabeth Sowell, Lindsay Squeglia, Susan Tapert, Lucina Uddin, Sylia Wilson, Deborah Yurgelun-Todd, Andrea Foulkes, and Melissa Stockwell. 2024. “Characterizing Long COVID in Children and Adolescents”. JAMA, 332, 14, Pp. 1174-88. doi:10.1001/jama.2024.12747
Abstract
IMPORTANCE: Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.OBJECTIVE: To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.DESIGN, SETTING, AND PARTICIPANTS: Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.EXPOSURE: SARS-CoV-2 infection.MAIN OUTCOMES AND MEASURES: PASC and 89 prolonged symptoms across 9 symptom domains.RESULTS: A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.CONCLUSIONS AND RELEVANCE: This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.