Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

2022

e2223253

07/2022

2574-3805

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children.

Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs.

Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls.

Exposure: SARS-CoV-2 detected via nucleic acid testing.

Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey.

Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]).

Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

10.1001/jamanetworkopen.2022.23253

JAMA Netw Open

35867061

Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.

2022

e2142322

2022 01 04

2574-3805

<p><strong>Importance: </strong>Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized.</p>

<p><strong>Objective: </strong>To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED).</p>

<p><strong>Design, Setting, and Participants: </strong>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.</p>

<p><strong>Exposures: </strong>Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing.</p>

<p><strong>Main Outcomes and Measures: </strong>Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death.</p>

<p><strong>Results: </strong>Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (&gt;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 &lt;10 years vs &lt;1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to &lt;18 years vs &lt;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%).</p>

<p><strong>Conclusions and Relevance: </strong>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.</p>

10.1001/jamanetworkopen.2021.42322

JAMA Netw Open

35015063

Predicting Adverse Outcomes for Shiga Toxin-Producing E. coli Infections in Emergency Departments.

2021

2021 Jan 05

1097-6833

<p><strong>OBJECTIVE: </strong>To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting.</p>

<p><strong>STUDY DESIGN: </strong>We reviewed medical records of children &lt;18 years old infected with STEC and treated in one of 38 participating EDs in North America between 2011 and 2015. The HUS severity score [hemoglobin (g/dL) plus two-times serum creatinine (mg/dL)] was calculated using first available laboratory results. Children with scores &gt;13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure and death) using discrimination and net benefit (i.e. threshold probability), with subgroup analyses by age and day-of-illness.</p>

<p><strong>RESULTS: </strong>A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (AUC 0.71, 95% CI 0.63, 0.79) and better among children &lt;5 years old (AUC 0.77, 95% CI 0.68, 0.87). For children &lt;5 years, greatest net benefit was achieved for a threshold probability &gt;26%.</p>

<p><strong>CONCLUSIONS: </strong>The HUS severity score was able to discriminate between high- and low-risk children &lt;5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.</p>

10.1016/j.jpeds.2020.12.077

J Pediatr

33417918

Assessment of primary outcome measures for a clinical trial of pediatric hemorrhagic injuries.

2020

2020 Mar 09

1532-8171

<p><strong>OBJECTIVE: </strong>We evaluated the acceptability of the Pediatric Quality of Life Inventory (PedsQL) and other outcomes as the primary outcomes for a pediatric hemorrhagic trauma trial (TIC-TOC) among clinicians.</p>

<p><strong>METHODS: </strong>We conducted a mixed-methods study that included an electronic questionnaire followed by teleconference discussions. Participants confirmed or rejected the PedsQL as the primary outcome for the TIC-TOC trial and evaluated and proposed alternative primary outcomes. Responses were compiled and a list of themes and representative quotes was generated.</p>

<p><strong>RESULTS: </strong>73 of 91 (80%) participants completed the questionnaire. 61 (84%) participants agreed that the PedsQL is an appropriate primary outcome for children with hemorrhagic brain injuries. 32 (44%) participants agreed that the PedsQL is an acceptable primary outcome for children with hemorrhagic torso injuries, 27 (38%) participants were neutral, and 13 (18%) participants disagreed. Several themes were identified from responses, including that the PedsQL is an important and patient-centered outcome but may be affected by other factors, and that intracranial hemorrhage progression assessed by brain imaging (among patients with brain injuries) or blood product transfusion requirements (among patients with torso injuries) may be more objective outcomes than the PedsQL.</p>

<p><strong>CONCLUSIONS: </strong>The PedsQL was a well-accepted proposed primary outcome for children with hemorrhagic brain injuries. Traumatic intracranial hemorrhage progression was favored by a subset of clinicians. A plurality of participants also considered the PedsQL an acceptable outcome for children with hemorrhagic torso injuries. Blood product transfusion requirement was favored by fewer participants.</p>

10.1016/j.ajem.2020.03.001

Am J Emerg Med

32278572

Intravenous Magnesium in Asthma Pharmacotherapy: Variability in Use in the PECARN Registry.

2020

2020 Mar 05

1097-6833

<p><strong>OBJECTIVE: </strong>To examine the use, efficacy, and safety of intravenous magnesium sulfate (IVMg) in children with asthma whose emergency department (ED) management is recorded in the Pediatric Emergency Care Applied Research Network (PECARN) Registry.</p>

<p><strong>STUDY DESIGN: </strong>This multicenter retrospective cohort study analyzed clinical data from 7 EDs from 2012 to 2017. We described use of IVMg in children aged 2-17&nbsp;years treated for acute asthma and its effect on blood pressure. We also used multivariable analysis to examine factors associated with use of IVMg and its association with return visits within 72&nbsp;hours.</p>

<p><strong>RESULTS: </strong>Across 61 854 asthma visits for children, clinicians administered IVMg in 6497 (10.5%). Median time from triage to IVMg administration was 154&nbsp;minutes (IQR 84, 244). During 22 495 ED visits resulting in hospitalization after ED treatment, IVMg was administered in 5774 (25.7%) (range by site 15.9%, 50.6%). Patients were discharged home from the ED after 11.1% of IVMg administrations, and hypotension occurred after 6.8%. Variation in IVMg use was not explained by patient characteristics. Revisits did not differ between patients discharged after IVMg and those not receiving IVMg.</p>

<p><strong>CONCLUSIONS: </strong>In PECARN Registry EDs, administration of IVMg occurs late in ED treatment, for a minority of the children likely to benefit, with variation between sites, which suggests the current clinical role for IVMg in preventing hospitalization is limited. Discharge after IVMg administration is likely safe. Further research should prospectively assess the efficacy and safety of early IVMg administration.</p>

10.1016/j.jpeds.2020.01.062

J. Pediatr.

32147221

Predicting Hemolytic Uremic Syndrome and Renal Failure in Shiga Toxin-Producing Escherichia coli Infected Children.

2019

2019 May 24

1537-6591

<p><strong>BACKGROUND: </strong>Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care.</p>

<p><strong>METHODS: </strong>We conducted a multicenter, historical-cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children &lt;18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible.</p>

<p><strong>RESULTS: </strong>Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors of HUS included younger age (OR: 0.77; 95%CI: 0.69, 0.85/year), leukocyte count ≥13.0x103/μL (2.54; 1.42, 4.54), higher hematocrit (1.83; 1.21, 2.77/5% increase) and serum creatinine (10.82; 1.49, 78.69/1 mg/dL increase), platelet count &lt;250 ×103/μL (1.92; 1.02, 3.60), lower serum sodium (1.12; 1.02, 1.23/1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50; 1.14, 5.46). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (0.70; 0.54, 0.90). RRT predictors included female sex (2.27; 1.14, 4.50), younger age (0.83; 0.74, 0.92/year), lower serum sodium (1.15; 1.04, 1.27/mmol/L decrease), higher leukocyte count ≥13.0x103/μL (2.35; 1.17, 4.72) and creatinine (7.75; 1.20, 50.16/1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71; 1.18, 6.21).</p>

<p><strong>CONCLUSIONS: </strong>The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.</p>

10.1093/cid/ciz432

Clin. Infect. Dis.

31125419