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. 2025 May 27;179(7):781-792.
doi: 10.1001/jamapediatrics.2025.1066. Online ahead of print.

Characterizing Long COVID Symptoms During Early Childhood

Rachel S Gross  1 , Tanayott Thaweethai  2   3 , Amy L Salisbury  4 , Lawrence C Kleinman  5   6 , Sindhu Mohandas  7 , Kyung E Rhee  8 , Jessica N Snowden  9 , Kelan G Tantisira  10 , David Warburton  11 , John C Wood  12 , Patricia A Kinser  4 , Joshua D Milner  13 , Erika B Rosenzweig  14 , Katherine Irby  15 , Valerie J Flaherman  16 , Elizabeth W Karlson  17   18 , Lori B Chibnik  2   19 , Deepti B Pant  2 , Aparna Krishnamoorthy  2 , Richard Gallagher  20 , Michelle F Lamendola-Essel  21 , Denise C Hasson  22 , Stuart D Katz  23 , Shonna Yin  1   24 , Benard P Dreyer  25 , Frank Blancero  26 , Megan Carmilani  26   27 , K Coombs  26   28 , Megan L Fitzgerald  26   29 , Rebecca J Letts  26 , Aimee K Peddie  26 , Judy L Aschner  30 , Andrew M Atz  31 , Dithi Banerjee  32 , Amanda Bogie  33 , Hulya Bukulmez  34 , Katharine Clouser  35 , Lesley A Cottrell  36 , Kelly Cowan  37 , Viren A D'Sa  38 , Allen Dozor  39 , Amy J Elliott  40 , E Vincent S Faustino  41 , Alexander G Fiks  42 , Sunanda Gaur  43 , Maria L Gennaro  44 , Stewart Gordon  45 , Uzma N Hasan  46 , Christina M Hester  47 , Alexander Hogan  48 , Daniel S Hsia  49 , David C Kaelber  50 , Jessica S Kosut  51 , Sankaran Krishnan  39 , Russell J McCulloh  52 , Ian C Michelow  53 , Sheila M Nolan  54 , Carlos R Oliveira  55 , Lynn M Olson  56 , Wilson D Pace  47 , Paul Palumbo  57 , Hengameh Raissy  58 , Andy Reyes  35 , Judith L Ross  59 , Juan C Salazar  53 , Rangaraj Selvarangan  60 , Cheryl R Stein  61 , Michelle D Stevenson  62 , Ronald J Teufel  63 , Alan Werzberger  64 , John M Westfall  47 , Kathleen Zani  65 , William T Zempsky  48 , Emily Zimmerman  66 , Marie-Abele C Bind  2   3 , James Chan  2 , Zoe Guan  2   3 , Richard E Morse  2 , Harrison T Reeder  2   3 , Torri D Metz  67 , Jane W Newburger  68 , Dongngan T Truong  69 , Andrea S Foulkes  2   3   70 , Melissa S Stockwell  71   72 ; RECOVER-Pediatrics Consortium; RECOVER-Pediatrics Group Authors
Collaborators, Affiliations

Characterizing Long COVID Symptoms During Early Childhood

Rachel S Gross et al. JAMA Pediatr. .

Erratum in

  • Change to Open Access Status.
    [No authors listed] [No authors listed] JAMA Pediatr. 2025 Aug 1;179(8):930. doi: 10.1001/jamapediatrics.2025.2389. JAMA Pediatr. 2025. PMID: 40690238 Free PMC article. No abstract available.

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Snowden reported serving on a Pfizer COVID-19 advisory board outside the submitted work, which ended in November 2023. Dr Milner reported serving on a scientific advisory board for Blueprint Medicine during the conduct of the study. Dr Aschner reported being a Gilead Sciences stockholder during the conduct of the study. Dr Werzberger reported receiving funding from Merck for a hepatitis A vaccine immunology study outside the submitted work. Dr Zempsky reported having affiliations with Ommio Health, Lundbeck Pharmacueticals, and Editas during the conduct of the study. Dr Metz reported being a site principal investigator for Pfizer studies of SARS-CoV-2 vaccination in pregnancy, respiratory syncytial virus vaccination in pregnancy, and Paxlovid (Pfizer) in pregnancy outside the submitted work Dr Truong reported being co–principal investigator on a Pfizer-funded study to assess long-term sequalae of vaccine associated myocarditis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Identification of the Optimal Threshold for Long COVID (LC) Using the LC Research Index
A, Infants and toddlers. B, Preschool-aged children. The optimal research index threshold for LC was selected to distinguish between participants with probable LC and unspecified LC using bootstrapping to estimate error bars (95% CIs shown). The dashed horizontal line and shading indicates the threshold for optimal identification of LC-probable status. An approximation of the elbow method was used to identify the cutoff where the number of uninfected participants misclassified as having probable LC stabilized (eMethods in the Supplement 1). The threshold, an index of 4 or greater in infants/toddlers and 3 or greater in preschool-aged children, can be used to identify young children with LC for research purposes. Using this threshold, the percentage of infected infants and toddlers with probable LC with each symptom was as follows: poor appetite, 52%; trouble sleeping, 28%; wet cough, 45%; dry cough, 25%; and stuffy nose, 57%. The percentage of infected preschool-aged children with probable LC with each symptom was as follows: daytime tiredness/sleepiness or low energy, 33%; and dry cough, 74%.
Figure 2.
Figure 2.. Long COVID (LC) Research Index and Patient-Reported Outcomes Measurement Information System (PROMIS) Early Childhood Parent Report Global Health Scales
A, Infants and toddlers. B, Preschool-aged children. Caregiver responses to 4 questions from the PROMIS early childhood parent report global health scales survey were reported, stratified into groups. Two groups are the same for both age groups: participants with a zero LC research index and no prolonged symptoms and participants with a zero LC research index but at least 1 prolonged symptom that does not contribute to the index. In infants and toddlers, there are 2 additional groups: those with nonzero research indices but not meeting the threshold for LC (0.5-3.5), and those with research indices that meet the threshold (4-15.5, the maximum). In preschool-aged children, there is 1 additional group: participants with either of the 2 symptoms that contribute to the LC research index, thus reaching the threshold for LC (3-9.5). The thick vertical black line indicates the threshold for LC. The shading in each cell is proportional to the reported frequency of each response.
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Cited by

  • Change to Open Access Status.
    [No authors listed] [No authors listed] JAMA Pediatr. 2025 Aug 1;179(8):930. doi: 10.1001/jamapediatrics.2025.2389. JAMA Pediatr. 2025. PMID: 40690238 Free PMC article. No abstract available.

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