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. 2022 Oct 1;176(10):1000-1009.
doi: 10.1001/jamapediatrics.2022.2800.

Clinical Features and Burden of Postacute Sequelae of SARS-CoV-2 Infection in Children and Adolescents

Suchitra Rao  1 , Grace M Lee  2 , Hanieh Razzaghi  3 , Vitaly Lorman  3 , Asuncion Mejias  4 , Nathan M Pajor  5 , Deepika Thacker  6 , Ryan Webb  3 , Kimberley Dickinson  3 , L Charles Bailey  3 , Ravi Jhaveri  7 , Dimitri A Christakis  8   9 , Tellen D Bennett  1 , Yong Chen  10 , Christopher B Forrest  3
Affiliations

Clinical Features and Burden of Postacute Sequelae of SARS-CoV-2 Infection in Children and Adolescents

Suchitra Rao et al. JAMA Pediatr. .

Abstract

Importance: The postacute sequelae of SARS-CoV-2 infection (PASC) has emerged as a long-term complication in adults, but current understanding of the clinical presentation of PASC in children is limited.

Objective: To identify diagnosed symptoms, diagnosed health conditions, and medications associated with PASC in children.

Design, setting and participants: This retrospective cohort study used electronic health records from 9 US children's hospitals for individuals younger than 21 years who underwent antigen or reverse transcriptase-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 between March 1, 2020, and October 31, 2021, and had at least 1 encounter in the 3 years before testing.

Exposures: SARS-CoV-2 positivity by viral test (antigen or RT-PCR).

Main outcomes and measures: Syndromic (symptoms), systemic (conditions), and medication PASC features were identified in the 28 to 179 days following the initial test date. Adjusted hazard ratios (aHRs) were obtained for 151 clinically predicted PASC features by contrasting viral test-positive groups with viral test-negative groups using proportional hazards models, adjusting for site, age, sex, testing location, race and ethnicity, and time period of cohort entrance. The incidence proportion for any syndromic, systemic, or medication PASC feature was estimated in the 2 groups to obtain a burden of PASC estimate.

Results: Among 659 286 children in the study sample, 348 091 (52.8%) were male, and the mean (SD) age was 8.1 (5.7) years. A total of 59 893 (9.1%) tested positive by viral test for SARS-CoV-2, and 599 393 (90.9%) tested negative. Most were tested in outpatient testing facility settings (322 813 [50.3%]) or office settings (162 138 [24.6%]). The most common syndromic, systemic, and medication features were loss of taste or smell (aHR, 1.96; 95% CI, 1.16-3.32), myocarditis (aHR, 3.10; 95% CI, 1.94-4.96), and cough and cold preparations (aHR, 1.52; 95% CI, 1.18-1.96), respectively. The incidence of at least 1 systemic, syndromic, or medication feature of PASC was 41.9% (95% CI, 41.4-42.4) among viral test-positive children vs 38.2% (95% CI, 38.1-38.4) among viral test-negative children, with an incidence proportion difference of 3.7% (95% CI, 3.2-4.2). A higher strength of association for PASC was identified in those cared for in the intensive care unit during the acute illness phase, children younger than 5 years, and individuals with complex chronic conditions.

Conclusions and relevance: In this large-scale, exploratory study, the burden of pediatric PASC that presented to health systems was low. Myocarditis was the most commonly diagnosed PASC-associated condition. Acute illness severity, young age, and comorbid complex chronic disease increased the risk of PASC.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Rao has received grants from the National Institutes of Health during the conduct of the study as well as grants from Biofire and consulting fees from Sequiris outside the submitted work. Dr Lee has received grants from the National Institutes of Health RECOVER during the conduct of the study as well as personal fees from United Health Group outside the submitted work. Dr Mejias has received grants from the National Institutes of Health during the conduct of the study; grants from Janssen and Merck; and personal fees from Janssen, Sanofi-Pasteur, Merck, and AstraZeneca outside the submitted work. Dr Bailey has received grants from the National Institutes of Health and Patient-Centered Outcomes Research Institute during the conduct of the study. Dr Jhaveri has received personal fees from AstraZeneca, Seqirus, Dynavax, and Elsevier outside the submitted work. Dr Bennett has received grants from the National Institutes of Health during the conduct of the study and grants from the National Institutes of Health outside the submitted work. Dr Forrest has received grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Syndromic Features of Postacute Sequelae of SARS-CoV-2 Infection
Adjusted hazard ratios (aHRs) with associated 95% CIs among patients who tested positive for SARS-CoV-2 infection vs those who tested negative for the risk of each syndromic feature using Cox proportional hazards models. Models were adjusted for age at cohort entrance, sex, race and ethnicity, institution, testing place location, presence of a complex medical condition, and date of cohort entrance.
Figure 2.
Figure 2.. Systemic Features of Postacute Sequelae of SARS-CoV-2 Infection
Adjusted hazard ratios (aHRs) with associated 95% CIs among patients who tested positive for SARS-CoV-2 infection vs those who tested negative for the risk of each systemic feature using Cox proportional hazards models. Models were adjusted for age at cohort entrance, sex, race and ethnicity, institution, testing place location, and date of cohort entrance. For each health condition evaluated, patients with evidence of that condition 18 months before cohort entrance were excluded from the denominator to identify incident cases. Each ratio compares the risk of the outcome in children who tested positive for SARS-CoV-2 infection vs those who tested negative. The diagnostic cluster for COVID-19 indicates children receiving care for the illness in the postacute period.
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