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Characterizing Long COVID in children and adolescents

Gross, RS; Thaweethai, T; Kleinman, LC; et al., JAMA

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Published

August 2024

Journal

JAMA

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. 

Authors

Rachel S Gross, Tanayott Thaweethai, Lawrence C Kleinman, Jessica N Snowden, Erika B Rosenzweig, Joshua D Milner, Kelan G Tantisira, Kyung E Rhee, Terry L Jernigan, Patricia A Kinser, Amy L Salisbury, David Warburton, Sindhu Mohandas, John C Wood, Jane W Newburger, Dongngan T Truong, Valerie J Flaherman, Torri D Metz, Elizabeth W Karlson, Lori B Chibnik, Deepti B Pant, Aparna Krishnamoorthy, Richard Gallagher, Michelle F Lamendola-Essel, Denise C Hasson, Stuart D Katz, Shonna Yin, Benard P Dreyer, Megan Carmilani, K Coombs, Megan L Fitzgerald, Nick Güthe, Mady Hornig, Rebecca J Letts, Aimee K Peddie, Brittany D Taylor, Andrea S Foulkes, Melissa S Stockwell, ; RECOVER-Pediatrics Consortium; RECOVER-Pediatrics Group Authors
Venkataraman Balaraman, Amanda Bogie, Hulya Bukulmez, Allen J Dozor, Daniel Eckrich, Amy J Elliott, Danielle N Evans, Jonathan S Farkas, E Vincent S Faustino, Laura Fischer, Sunanda Gaur, Ashraf S Harahsheh, Uzma N Hasan, Daniel S Hsia, Gredia Huerta-Montañez, Kathy D Hummel, Matt P Kadish, David C Kaelber, Sankaran Krishnan, Jessica S Kosut, Jerry Larrabee, Peter Paul C Lim, Ian C Michelow, Carlos R Oliveira, Hengameh Raissy, Zaira Rosario-Pabon, Judith L Ross, Alice I Sato, Michelle D Stevenson, Maria M Talavera-Barber, Ronald J Teufel, Kathryn E Weakley, Emily Zimmerman, Marie-Abele C Bind, James Chan, Zoe Guan, Richard E Morse, Harrison T Reeder, Natascha Akshoomoff, Judy L Aschner, Rakesh Bhattacharjee, Lesley A Cottrell, Kelly Cowan, Viren A D'Sa, Alexander G Fiks, Maria L Gennaro, Katherine Irby, Manaswitha Khare, Jeremy Landeo Guttierrez, Russell J McCulloh, Shalu Narang, Manette Ness-Cochinwala, Sheila Nolan, Paul Palumbo, Julie Ryu, Juan C Salazar, Rangaraj Selvarangan, Cheryl R Stein, Alan Werzberger, William T Zempsky, Robin Aupperle, Fiona C Baker, Marie T Banich, Deanna M Barch, Arielle Baskin-Sommers, James M Bjork, Susan Y Bookheimer, Sandra A Brown, B J Casey, Linda Chang, Duncan B Clark, Anders M Dale, Mirella Dapretto, Thomas M Ernst, Damien A Fair, Sarah W Feldstein Ewing, John J Foxe, Edward G Freedman, Naomi P Friedman, Hugh Garavan, Dylan G Gee, Raul Gonzalez, Kevin M Gray, Mary M Heitzeg, Megan M Herting, Joanna Jacobus, Angela R Laird, Christine L Larson, Krista M Lisdahl, Monica Luciana, Beatriz Luna, Pamela A F Madden, Erin C McGlade, Eva M Müller-Oehring, Bonnie J Nagel, Michael C Neale, Martin P Paulus, Alexandra S Potter, Perry F Renshaw, Elizabeth R Sowell, Lindsay M Squeglia, Susan Tapert, Lucina Q UddinSylia WilsonDeborah A Yurgelun-Todd

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Short Summary

This RECOVER study is one of the first of its kind to look at Long COVID symptoms in children across age groups. Researchers for this study also developed a new research tool to help identify children who were most likely to have Long COVID. The study asked about prolonged or long-lasting symptoms in both school-age children (ages 6 to 11 years old) and teenagers (ages 12 to 17 years old) and compared these symptoms between those with and without a history of a COVID infection. The symptoms that were most likely to identify school-age children with Long COVID were trouble with memory or focusing, back or neck pain, stomach pain, headache, fears, refusing to go to school, skin rashes, trouble sleeping, nausea or vomiting, and lightheadedness or dizziness. The symptoms that were most likely to identify teenagers with Long COVID included change or loss of smell or taste, bone, muscle or joint pain, back or neck pain, feeling tired all day or after walking, having low energy, trouble with memory or focusing, headache, and lightheadedness or dizziness. These study findings show Long COVID symptoms can affect almost every organ system in the body. It also showed that while many of the symptoms between the two age groups were similar, there were differences. Understanding why these differences occur can help create future Long COVID treatments for children that are age-group specific. Read the Research Q&A

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