Saliva microRNA Profile in Children with and without Severe SARS-CoV-2 Infection.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) may impair immune modulating host microRNAs, causing severe disease. Our objectives were to determine the salivary miRNA profile in children with SARS-CoV-2 infection at presentation and compare the expression in those with and without severe outcomes. Children <18 years with SARS-CoV-2 infection evaluated at two hospitals between March 2021 and February 2022 were prospectively enrolled. Severe outcomes included respiratory failure, shock or death. Saliva microRNAs were quantified with RNA sequencing. Data on 197 infected children (severe = 45) were analyzed. Of the known human miRNAs, 1606 (60%) were measured and compared across saliva samples. There were 43 miRNAs with ≥2-fold difference between severe and non-severe cases (adjusted p-value < 0.05). The majority (31/43) were downregulated in severe cases. The largest between-group differences involved miR-4495, miR-296-5p, miR-548ao-3p and miR-1273c. These microRNAs displayed enrichment for 32 gene ontology pathways including viral processing and transforming growth factor beta and Fc-gamma receptor signaling. In conclusion, salivary miRNA levels are perturbed in children with severe COVID-19, with the majority of miRNAs being down regulated. Further studies are required to validate and determine the utility of salivary miRNAs as biomarkers of severe COVID-19.

Comparison of Trauma and Burn Evaluations in a Pediatric Emergency Department During Pre, Early and Late COVID-19 Pandemic.

BACKGROUND: Pediatric trauma epidemiology altered during early COVID-19 pandemic period but the impact of the ongoing pandemic is unknown. OBJECTIVES: To compare pediatric trauma epidemiology between the pre, early and late pandemic periods and to evaluate the association of race and ethnicity on injury severity during the pandemic. METHODS: We performed a retrospective study of trauma consults for an injury/burn in children ≤16 years between January 1, 2019 and December 31, 2021. Study period was categorized into pre (January 1, 2019-February 28, 2020), early (March 1, 2020-December 31, 2020), and late (January 1, 2021-December 31, 2021) pandemic. Demographics, etiology, injury/burn severity, interventions and outcomes were noted. RESULTS: A total of 4940 patients underwent trauma evaluation. Compared to pre-pandemic, trauma evaluations for injuries and burns increased during both the early (RR: 2.13, 95% CI: 1.6-2.82 and RR: 2.24, 95% CI: 1.39-3.63, respectively) and late pandemic periods (RR: 1.42, 95% CI: 1.09-1.86 and RR: 2.44, 95% CI: 1.55-3.83, respectively). Severe injuries, hospital admissions, operations and death were higher in the early pandemic but reverted to pre-pandemic levels during late pandemic. Non-Hispanic Blacks had an approximately 40% increase in mean ISS during both pandemic periods though they had lower odds of severe injury during both pandemic periods. CONCLUSIONS: Trauma evaluations for injuries and burns increased during the pandemic periods. There was a significant association of race and ethnicity with injury severity which varied with pandemic periods. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Features of an Atypical RSV Surge During the COVID-19 Pandemic.

This study describes the clinical features, severity, and outcomes in children <5 years of age with respiratory syncytial virus (RSV) infection during an atypical summer surge during the coronavirus disease 2019 (COVID-19) pandemic. Although timing was uncharacteristic, clinical features and illness severity were representative of a typical RSV season. Co-infection with SARS-CoV-2 was low.

Comparison of trauma and burn evaluations in a pediatric emergency department during pre, early and late COVID- 19 pandemic

Background Pediatric trauma epidemiology altered during early COVID-19 pandemic period but the impact of the ongoing pandemic is unknown. Objectives To compare pediatric trauma epidemiology between the pre, early and late pandemic periods and to evaluate the association of race and ethnicity on injury severity during the pandemic. Methods We performed a retrospective study of trauma consults for an injury/burn in children ≤ 16 years between January 1, 2019–December 31, 2021. Study period was categorized into pre (January 1, 2019–February 28, 2020), early (March 1, 2020–December 31, 2020), and late (January 1, 2021–December 31, 2021) pandemic. Demographics, etiology, injury/burn severity, interventions and outcomes were noted. Results A total of 4940 patients underwent trauma evaluation. Compared to pre-pandemic, trauma evaluations for injuries and burns increased during both the early (RR: 2.13, 95% CI: 1.6–2.82 and RR: 2.24, 95% CI: 1.39–3.63 respectively) and late pandemic periods (RR: 1.42, 95% CI: 1.09–1.86 and RR: 2.44, 95% CI: 1.55–3.83 respectively). Severe injuries, hospital admissions, operations and death were higher in the early pandemic but reverted to pre-pandemic levels during late pandemic. Non-Hispanic Blacks had an approximately 40% increase in mean ISS during both pandemic periods though they had lower odds of severe injury during both pandemic periods. Conclusions Trauma evaluations for injuries and burns increased during the pandemic periods. There was a significant association of race and ethnicity with injury severity which varied with pandemic periods. Level of Evidence Retrospective comparative study, Level III.

Association of Area Deprivation Index With Severity of COVID-19 in Pediatric Patients: A Multisite Study of Racially and Ethnically Diverse Children.

Area deprivation index (ADI) is associated with the risk of severe COVID-19 in adults. However, this association has not been established in children. Information on ADI, demographics, clinical features, disease severity, and outcomes was analyzed for 3434 children with COVID-19. A multivariate logistic regression revealed that non-Hispanic Asians, extremes of weight, and higher ADI were associated with severe disease.

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

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.

Social Determinants of Severe Injury Among Pediatric Patients During the COVID-19 Pandemic: An Exploratory Study.

INTRODUCTION: This study sought to identify social determinants of health (SDH) patterns associated with severe pediatric injuries. METHOD: We used cross-sectional data from children (≤18 years) admitted to a pediatric trauma center between March and November 2021 (n = 360). We used association rule mining (ARM) to explore SDH patterns associated with severe injury. We then used ARM-identified SDH patterns in multivariable logistic regressions of severe injury, controlling for patient and caregiver demographics. Finally, we compared results to naive hierarchical logistic regressions that considered SDH types as primary exposures rather than SDH patterns. RESULTS: We identified three SDH patterns associated with severe injury: (1) having child care needs in combination with neighborhood violence, (2) caregiver lacking health insurance, and (3) caregiver lacking social support. In the ARM-informed logistic regression models, the presence of a child care need in combination with neighborhood violence was associated with an increased odds of severe injury (aOR, 2.77; 95% CI, 1.01-7.62), as was caregiver lacking health insurance (aOR, 2.29; 95% CI, 1.02-5.16). In the naive hierarchical logistic regressions, no SDH type in isolation was associated with severe injury. DISCUSSION: Our exploratory analyses suggest that considering the co-occurrence of negative SDH that families experience rather than isolated SDH may provide greater insights into prevention strategies for severe pediatric injury.

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

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. Objective: 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. Exposures: 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. Results: 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.

MIS-C among return visits for fever in a pediatric emergency department during the COVID-19 pandemic.

Return visits (RV) to a pediatric emergency department (PED) can be secondary to illness progression, parental concerns, call backs or rarely due to a diagnostic error during the first visit. Fever accounts for nearly half of these RVs and is also one of the most common presenting complaints of Corona Virus Disease 2019 (COVID- 19) due to severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection in children. Although majority of children with COVID 19 have a mild illness, severe complications such as Multisystem inflammatory syndrome in children (MIS-C) can occur. These children are often critically ill with a mortality rate of 2-4%. Initial symptoms of MIS- C are non- specific and mimic other viral illness making early diagnosis challenging. We report five patients who were evaluated for fever and discharged from our PED and were subsequently diagnosed with MIS-C (n = 3) or Kawasaki Disease (n = 2) during their RV within 7 days. All patients presented with fever during the initial visit and three of the five children had gastrointestinal symptoms. They were all noted have persistent tachycardia during the index visit. Three patients presented in cardiogenic shock and echocardiographic abnormalities were noted in four patients during the RV. Significant interventions were required in majority of these children (PICU admission: 4, inotropes: 3, mechanical ventilation:2). Clinicians need to maintain a high index of suspicion for diagnosis of MIS-C especially in those who present with persistent fever and have abnormal vital signs during the COVID-19 pandemic.

Trauma Visits to a Pediatric Emergency Department During the COVID-19 Quarantine and "Stay at Home" Period.

BACKGROUND: Impact of social distancing on pediatric injuries is unknown. METHODS: We retrospectively compared injury visits to a pediatric emergency department by individuals ≤21 years during "Stay at Home" (SHO) period to the same period in 2019 (non-SHO). Demographics, types, and outcomes of injuries were noted. RESULTS: Although, there was a 35.6% reduction in trauma-related emergency department visits during SHO period (1226 vs 1904), the proportion of injury visits increased (15.5% vs 8.1%, P < .001) and mean age was lower (5.8 yrs ±4.5 vs 8.4 yrs ± 5.2, P < .001). There were significant increases in visits related to child physical abuse (CPA), firearms, and dog bites. Further, significant increases in trauma alerts (P < .01), injury severity (P < .01), critical care admissions (P < .001), and deaths (P < .01) occurred during the SHO period. CONCLUSIONS: Although overall trauma-related visits decreased during SHO, the proportion of these visits and their severity increased. Trauma visits related to child physical abuse, dog bites, and firearms increased. Further studies are required to assess the long-term impact of pandemic on pediatric trauma epidemiology.

Severe Acute Respiratory Syndrome-Coronavirus-2 Transmission in an Urban Community: The Role of Children and Household Contacts.

This is a single-center US retrospective study of infection patterns among household sick contacts (HHSCs) of children with confirmed severe acute respiratory syndrome-coronavirus-2 infection in an urban setting. An HHSC was identified in fewer than half (42%) of the patients, and no child-to-adult transmission was identified. This is a single center US retrospective study of infection patterns among household sick contacts of children with confirmed SARS-CoV-2 infection. A household sick contact was identified in fewer than half (42%) of patients and no child-to-adult transmission was identified.

COVID-19 among Minority Children in Detroit, Michigan during the Early National Surge of the Pandemic.

Background. The COVID-19 pandemic has shed light on communities of racial/ethnic minority groups in the US where long-standing health issues and structural inequities are now known to have resulted in increased risk for infection, severe illness, and death from the virus. The objective of our study was to describe demographic characteristics, clinical presentations, medical interventions and outcomes of pediatric patients with COVID-19 treated at Children's Hospital of Michigan (CHM), a tertiary care center in urban Detroit, an early hotspot during the initial surge of the SARS-CoV-2 pandemic. Methods. A retrospective chart review was performed of children ≤18 years of age who had polymerase chain reaction (RT-PCR) testing via NP swab or serum IgG antibody testing for SARS-CoV-2 during March 1, 2020-June 30, 2020. Results. Seventy-eight COVID-19 infected children were identified of whom 85.8% (67/78) were from minority populations (African American, Hispanic). Hospitalization rate was 82% (64/78). About 44% (34/78) had an associated comorbidity with asthma and obesity being most common. Although all ages were affected, infants <1 year of age had the highest hospitalization rate (19/64, 30%). In all disease severity categories, dichotomized non-whites had more severe disease by percentage within race/ethnicity than Whites, and also within percent disease severity (P-value = .197). Overall, 37% of hospitalized patients required intensive care. Conclusions. Extremely high rates of COVID-19 hospitalization and requirement of ICU care were identified in our patient population. Further studies are needed to better understand the contributing factors to this health disparity in disadvantaged communities.

Multisystem inflammatory syndrome in children associated with novel coronavirus SARS-CoV-2: Presentations to a pediatric emergency department in Michigan.

The SARS-CoV-2 is a respiratory virus of the coronavirus family responsible for a global pandemic since December 2019. More than 35 million people have been affected with the novel coronavirus disease (COVID-19), with more than one million deaths worldwide. Michigan was one of the top three states in the United States that was severely affected by the SAR-CoV-2 pandemic with more than 7000 deaths in adults and greater than 145,000 confirmed infections. However, compared to adults, the majority of children until recently were either asymptomatic or had a mild illness with SARS-CoV-2. Recently, a rare but potentially serious presentation associated with SARS-CoV-2 called multisystem inflammatory syndrome in children (MIS-C) has been recently reported and the Centers for Disease Control (CDC) released a case definition for the same. We report the clinical and laboratory presentations and outcomes of 34 children with MIS-C who were evaluated within a 12 week period at a pediatric emergency department (PED) of single institution in Michigan. These cases presented approximately three weeks after the peak of adult SAR-CoV-2 related deaths occurred in the state. While many children presented with clinical characteristics similar to incomplete Kawasaki disease (KD), they also exhibited certain unique features which differentiated MIS-C from KD. The information presented below will aid clinicians with early recognition, evaluation and management of MIS-C in the emergency department.