Characterizing Long COVID Symptoms During Early Childhood, 2025, Gross et al.

SNT Gatchaman

SNT Gatchaman

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Characterizing Long COVID Symptoms During Early Childhood
Rachel S. Gross and 674 others

IMPORTANCE
Recent studies have identified characteristic symptom patterns of long COVID (LC) in adults and children older than 5 years. However, LC remains poorly characterized in early childhood. This knowledge gap limits efforts to identify, care for, and prevent LC in this vulnerable population.

OBJECTIVES
To identify symptoms that had the greatest difference in frequency comparing children with a history of SARS-CoV-2 infection to those without, to identify differences in the types of symptoms by age group (infants/toddlers [0-2 years] vs preschool-aged children [3-5 years]), and to derive an index that can be used in research studies to identify young children with LC.

DESIGN, SETTING, AND PARTICIPANTS
This was a multisite longitudinal cohort study with enrollment from over 30 US health care and community settings, including infants, toddlers, and preschool-aged children with and without SARS-CoV-2 infection history. Study data were analyzed from May to December 2024.

EXPOSURE
SARS-CoV-2 infection.

MAIN OUTCOMES AND MEASURES
LC and 41 symptoms among infants/toddlers and 75 symptoms among preschool-aged children.

RESULTS
The study included 472 infants/toddlers (mean [SD] age, 12 [9] months; 278 infected with SARS-CoV-2; 194 uninfected; 234 male [50%]; 73 Black or African American [16%]; 198 Hispanic, Latino, or Spanish [43%]; 242 White [52%]) and 539 preschool-aged children (mean [SD] age, 48 [10] months; 399 infected with SARS-CoV-2; 140 uninfected; 277 female [51%]; 70 Black or African American [13%]; 210 Hispanic, Latino, or Spanish [39%]; 287 White [54%]). The median (IQR) time between first infections and completion of symptom surveys was 318 (198-494) days for infants/toddlers and 520 (330-844) days for preschool-aged children. A research index was derived for each age group based on symptoms most associated with infection history. The index is calculated by summing scores assigned to each prolonged symptom that was present, where higher scores indicate greater magnitude of association with history of SARS-CoV-2 infection: poor appetite (5 points), trouble sleeping (3.5 points), wet cough (3.5 points), dry cough (3 points), and stuffy nose (0.5 points) for infants/toddlers, and daytime tiredness/sleepiness/low energy (6.5 points) and dry cough (3 points) for preschool-aged children. Among infants/toddlers with infection, 40 of 278 (14%) were classified as having probable LC by having an index of at least 4 points. Among preschool-aged children, 61 of 399 (15%) were classified as having probable LC by having an index of at least 3 points. Participants with higher indices often had poorer overall health, lower quality of life, and perceived delays in developmental milestones.

CONCLUSIONS AND RELEVANCE
This cohort study identified symptom patterns and derived research indices that were distinct between the 2 age groups and differed from those previously identified in older ages, demonstrating the need to characterize LC separately across age ranges.

Link | PDF (JAMA Pediatrics)
 
The findings that infants/toddlers and preschool-aged children have varied symptoms may be explained by the fact that symptoms in younger children are reported based on what caregivers can observe rather than what the children themselves are feeling and describing, because most children in this age group do not yet have the language, social skills, or understanding of symptoms to share what they are experiencing. For example, fears and feelings of pain, brain fog, headache, tiredness, or changes in taste and smell may be hard to identify if the child cannot verbalize their internal feelings or sensations, whereas a symptom such as cough is easily observed. A further complication is that the identified symptoms may occur commonly in young children because of their naive immune systems. Daytime sleepiness, trouble sleeping, cough, stuffy nose, and poor appetite can occur in many acute and chronic early childhood illnesses.
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https://www.eurekalert.org/news-releases/1085363

News Release 27-May-2025
Researchers identify key symptoms of long COVID in young children
Peer-Reviewed Publication

Mass General Brigham

Long COVID—symptoms that linger long after initial viral infection—can affect people of every age, including children. But the lasting symptoms in an infant, toddler, or pre-school-aged child may be different than symptoms in adults and older children. A new study conducted by researchers at Mass General Brigham and their colleagues as part of the federally funded RECOVER initiative examined the most common long COVID symptoms in young children, finding that infants and toddlers (younger than 2 years old) were more likely to experience trouble sleeping, fussiness, poor appetite, stuffy nose, and cough. Preschool-aged children (3 to 5 years old) were more likely to have a dry cough and daytime tiredness/low energy. Results are published in JAMA Pediatrics.

“This study is important because it shows that long COVID symptoms in young children are different from those in older children and adults,” said co-first author Tanayott (Tony) Thaweethai, PhD, associate director of Biostatistics Research and Engagement at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. Thaweethai is also an assistant professor at Harvard Medical School. “Children with these symptoms often had worse overall health, lower quality of life, and delays in development.”

The new study is the latest publication from National Institutes of Health (NIH)-funded Researching COVID to Enhance Recovery (RECOVER) initiative, which seeks to explore the effects of long COVID across all ages. This paper builds on a previously published study that examined long COVID symptoms in school-aged children (6 to 11 years old) and teenagers (12 to 17 years old). In this new study, Thaweethai and fellow RECOVER researchers focused on younger age groups, infants and toddlers and preschool-age children. The study included 472 infants/toddlers and 539 preschool-aged children, some of whom had previously had COVID and some who had not. Children were enrolled between March 2022 and July 2024 from over 30 U.S. health care and community settings.

Researchers looked at a variety of caregiver-reported symptoms lasting at least 90 days after COVID infection for both age groups—41 symptoms in the infant/toddler group and 75 symptoms among preschool-aged children. They compared children who had not been previously infected to those with a history of COVID to see which symptoms persisted. Among children who had been previously infected, 40 of 278 infants/toddlers (14%) and 61 of 399 preschool-aged children (15%) were classified as likely having long COVID.

“We found a distinguishable pattern for both age groups of young children, including symptoms that are different than what we see in older children and adults,” said co-senior author Andrea Foulkes, ScD, director of Biostatistics at MGH, professor in the Department of Medicine at Harvard Medical School, and professor in the Department of Biostatistics at the Harvard T.H. Chan School of Public Health. “The tools from this study can be used in future studies to better understand long COVID in young children and develop ways to care for them.”

The authors note that the symptoms reported in the paper have been identified for research purposes, not for making a clinical diagnosis and that caregivers should talk to a child’s clinician if they are concerned about symptoms of long COVID. They also note that their study relies on survey data, which can be affected by recall bias and may be difficult to report accurately for children too young to verbalize their symptoms and where antibody confirmation of infection may be incomplete.



Authorship: Mass General Brigham authors include Tanayott Thaweethai, Deepti B. Pant, Elizabeth W. Karlson, Lori B. Chibnik, Aparna Krishnamoorthy, Andrea S. Foulkes, Marie-Abele C. Bind , James Chan, Zoe Guan, Richard E. Morse, and Harrison T. Reeder. Additional authors include Rachel S. Gross, Amy L. Salisbury, Lawrence C. Kleinman, Sindhu Mohandas, Kyung E. Rhee, Jessica N. Snowden, Kelan G. Tantisira, David Warburton, John C. Wood, Patricia A. Kinser, Joshua D. Milner, Erika B. Rosenzweig, Katherine Irby, Valerie J. Flaherman, Richard Gallagher, Michelle F. Lamendola-Essel, Denise C. Hasson, Stuart D. Katz, Shonna Yin, Benard P. Dreyer, Frank Blancero, Megan Carmilani, K. Coombs, Megan L. Fitzgerald, Rebecca J. Letts, Aimee K. Peddie, Melissa S. Stockwell, and the RECOVER-Pediatrics Group Authors.

Disclosures: Snowden served on a Pfizer COVID-19 advisory board; Milner served on a scientific advisory board for Blueprint Medicine. Additional disclosures can be found in the paper published in JAMA Pediatrics.

Funding: This study was funded in part by the National Institutes of Health (OT2HL161841, OT2HL161847, OT2HL156812, R01 HL162373).

Paper cited: Gross, R. S. et al. “Characterizing Long COVID Symptoms During Early Childhood” JAMA Pediatrics DOI: 10.1001/jamapediatrics.2025.1066



Additional links:

 
https://www.eurekalert.org/news-releases/1085041

News Release 27-May-2025
Characterizing long COVID symptoms during early childhood

JAMA Pediatrics

Peer-Reviewed Publication
JAMA Network

About The Study: This cohort study identified symptom patterns and derived research indices that were distinct between the 2 age groups (infants/toddlers [0-2 years] vs preschool-aged children [3-5 years]) and differed from those previously identified in older ages, demonstrating the need to characterize long COVID separately across age ranges.

Corresponding Author: To contact the corresponding author, Rachel S. Gross, MD, MS, email rachel.gross@nyulangone.org.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2025.1066)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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