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What proportion of SARS-CoV-2–positive youths tested in emergency departments (ED) experience severe outcomes (ie, intensive interventions, severe organ impairment, or death) within 14 days?
Among 3221 SARS-CoV-2–positive youths enrolled in a global prospective cohort study with outcome data, 3.3% had severe outcomes within 14 days. Across a subgroup of 2510 SARS-CoV-2–positive youths discharged home after testing, 0.5% had severe outcomes during the 2-week follow-up period.
The findings of this study suggest that risk factors such as age, underlying chronic illness, and symptom duration may be useful for clinicians to consider when evaluating pediatric patients with SARS-CoV-2 infection.
Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized.
To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED).
Design, Setting, and Participants
This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021.
Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing.
Main Outcomes and Measures
Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death.
Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2–negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2–positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%).
Conclusions and Relevance
In this study, approximately 3% of SARS-CoV-2–positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: October 30, 2021.
Published: January 11, 2022. doi:10.1001/jamanetworkopen.2021.42322
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Funk AL et al. JAMA Network Open.
Corresponding Author: Stephen B. Freedman, MDCM, MSc, Sections of Pediatric Emergency Medicine and Gastroenterology, Departments of Pediatrics and Emergency Medicine, Cumming School of Medicine, University of Calgary, 28 Oki Dr NW, Calgary, AB T3H 5S7, Canada (email@example.com).
Author Contributions: Dr Funk had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Funk, Florin, Kuppermann, Tancredi, Neuman, Klassen, Freedman.
Acquisition, analysis, or interpretation of data: Funk, Florin, Kuppermann, Tancredi, Xie, Kim, Ambroggio, Plint, Mintegi, Salvadori, Malley, Payne, Simon, Yock-Corrales, Nebhrajani, Chaudhari, Breslin, Finkelstein, Campos, Bergmann, Bhatt, Ahmad, Gardiner, Avva, Shah, Sartori, Sabhaney, Caperell, Navanandan, Borland, Morris, Gangoiti, Pavlicich, Kannikeswaran, Lunoe, Rino, Kam, Cherry, Rogers, Chong, Palumbo, Angelats, Morrison, Kwok, Becker, Dixon, Poonai, Eckerle, Wassem, Dalziel, Freedman.
Drafting of the manuscript: Funk, Freedman.
Critical revision of the manuscript for important intellectual content: Funk, Florin, Kuppermann, Tancredi, Xie, Kim, Neuman, Ambroggio, Plint, Mintegi, Klassen, Salvadori, Malley, Payne, Simon, Yock-Corrales, Nebhrajani, Chaudhari, Breslin, Finkelstein, Campos, Bergmann, Bhatt, Ahmad, Gardiner, Avva, Shah, Sartori, Sabhaney, Caperell, Navanandan, Borland, Morris, Gangoiti, Pavlicich, Kannikeswaran, Lunoe, Rino, Kam, Cherry, Rogers, Chong, Palumbo, Angelats, Morrison, Kwok, Becker, Dixon, Poonai, Eckerle, Wassem, Dalziel, Freedman.
Statistical analysis: Funk, Tancredi, Xie.
Obtained funding: Funk, Florin, Kuppermann, Freedman.
Administrative, technical, or material support: Florin, Kuppermann, Xie, Freedman.
Supervision: Florin, Kuppermann, Mintegi, Dalziel, Freedman.
Conflict of Interest Disclosures: Dr Florin reported receiving grants from the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute outside the submitted work. Dr Ambroggio reported receiving grants from Pfizer outside the submitted work. Dr Malley reported receiving personal fees from Merck as a consultant, grants from Pfizer, grants from Astellas, and reported being a board member and consultant for Affinivax Scientific Founder outside the submitted work. Dr Morris reported royalties from intellectual property from UCSF Benioff Children's Hospital Oakland; grants from NIH/NHLBI, grants from FDA, and grants from NIH/NCCIM outside the submitted work; in addition, Dr Morris had a patent for therapeutics related to Arginine bioavailability in COVID-19 and MISC pending. Dr Becker reported receiving Primary Children's Hospital Fee per enrolled study participant from University of Utah during the conduct of the study. No other disclosures were reported.
Funding/Support: This study was supported by grants from the Canadian Institutes of Health Research (Operating Grant: COVID-19 – Clinical management), Alberta Innovates, the Alberta Health Services – University of Calgary – Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Dr Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund. Dr Freedman was supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Information: A complete list of the members of the Pediatric Emergency Research Network–COVID-19 Study Team appear in Supplement 2.
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