Clinical Features and Burden of Postacute Sequelae of SARS-CoV-2 Infection in Children and Adolescents
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Abstract
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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SciScore for 10.1101/2022.05.24.22275544: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The Children’s Hospital of Philadelphia’s Institutional Review Board designated this study as not human subjects’ research and waived informed consent.
Consent: The Children’s Hospital of Philadelphia’s Institutional Review Board designated this study as not human subjects’ research and waived informed consent.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our findings have limitations that warrant discussion. …
SciScore for 10.1101/2022.05.24.22275544: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The Children’s Hospital of Philadelphia’s Institutional Review Board designated this study as not human subjects’ research and waived informed consent.
Consent: The Children’s Hospital of Philadelphia’s Institutional Review Board designated this study as not human subjects’ research and waived informed consent.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our findings have limitations that warrant discussion. This EHR-based study identified symptoms, signs, and diagnoses that were significant enough to prompt health service use and be coded by clinicians as a reason for an encounter. Our approach may have missed some findings that may be stored in laboratory, procedural, radiological and other unstructured text data. The true burden of PASC may be underestimated from EHR data, with data from open health systems, with the potential for infrequent follow-up visits to academic centers of excellence for milder symptoms. For this reason, we limited our cohort to at least one visit in the prior three years, to identify active patients within the health system; similar strategies have been employed in other PEDSnet studies of COVID-19;39,40 the benefits of such approaches have been reported previously.41 However, this may underestimate the burden of PASC by excluding previously healthy children who did not have prior health encounters. Next, our test negative cohort may include individuals with SARS-CoV-2 infection who may have had testing conducted outside our health systems. These limitations may have biased results towards the null. Further, we did not identify specific race/ethnic groups as a risk factor for PASC despite the fact that SARS-CoV-2 disproportionally affects minority communities, which may reflect differences in care seeking behavior and access to care. Finally, children who tested positive may be more likely to seek...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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