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.

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.

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.

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.

Combined Hyperglycemic Hyperosmolar Syndrome and Diabetic Ketoacidosis Associated with COVID-19 in a Pediatric Patient

Although most children with coronavirus disease 2019 (COVID-19) are asymptomatic or only with mild symptoms, many symptomatic children still require admission to the intensive care unit. Multiple cases of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) associated with COVID-19 have been reported in adults. However, to our knowledge, only few similar cases have been published in the pediatric population. We report one of the first few severe cases of mixed HHS with DKA associated with COVID-19 in an adolescent. Our patient was successfully treated with intravenous immunoglobulin, Remdesivir, and methylprednisolone. As the pandemic continues, clinicians should be aware of this syndrome and consider early use of Remdesivir and corticosteroids. Further studies are required to understand the pathophysiology of this syndrome occurring with COVID-19. [ FROM AUTHOR] Copyright of Case Reports in Critical Care is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

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.

SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment.

This study was conducted to assess the clinical spectrum, management, and outcome of SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C). We reviewed medical records of children with MIS-C diagnosis seen at the Children's Hospital of Michigan in Detroit between April and June 2020. Thirty-three children were identified including 22 who required critical care (group 1) and 11 with less intense inflammation (group 2). Children in group 1 were older (median 7.0 years) than those in group 2 (median 2.0 years). Abdominal pain was present in 68% of patients in group 1. Hypotension or shock was present in 17/22 patients in group 1. Thirteen (39.4%) had Kawasaki disease (KD)-like manifestations. Five developed coronary artery dilatation; All resolved on follow-up. Intravenous immunoglobulin (IVIG) was given to all patients in group 1 and 7/11 in group 2. Second-line therapy was needed in 13/22 (group 1) for persisting inflammation or myocardial dysfunction; 12 received infliximab. All patients recovered.Conclusion: MIS-C clinical manifestations may overlap with KD; however, MIS-C is likely a distinct inflammatory process characterized by reversible myocardial dysfunction and rarely coronary artery dilatation. Supportive care, IVIG, and second-line therapy with infliximab were associated with a favorable outcome. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) manifestations include fever, gastrointestinal symptoms, shock, and occasional features of Kawasaki disease (KD). • Treatment includes immunomodulatory agents, most commonly IVIG and corticosteroids. What is New: • Spectrum of MIS-C varies from mild to severe inflammation and coronary artery dilatation occurred in 5/22 (23%) critically ill patients. • IVIG and infliximab therapy were associated with a favorable outcome including resolution of coronary dilatation; only 2/33 received corticosteroids.

Echocardiographic Indicators Associated with Adverse Clinical Course and Cardiac Sequelae in Multisystem Inflammatory Syndrome in Children with Coronavirus Disease 2019.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 causes significant cardiovascular involvement, which can be a determinant of clinical course and outcome. The aim of this study was to investigate whether echocardiographic measures of ventricular function were independently associated with adverse clinical course and cardiac sequelae in patients with MIS-C. METHODS: In a longitudinal observational study of 54 patients with MIS-C (mean age, 6.8 ± 4.4 years; 46% male; 56% African American), measures of ventricular function and morphometry at initial presentation, predischarge, and at a median of 3- and 10-week follow-up were retrospectively analyzed and were compared with those in 108 age- and gender-matched normal control subjects. The magnitude of strain is expressed as an absolute value. Risk stratification for adverse clinical course and outcomes were analyzed among the tertiles of clinical and echocardiographic data using analysis of variance and univariate and multivariate regression. RESULTS: Median left ventricular apical four-chamber peak longitudinal strain (LVA4LS) and left ventricular global longitudinal strain (LVGLS) at initial presentation were significantly decreased in patients with MIS-C compared with the normal cohort (16.2% and 15.1% vs 22.3% and 22.0%, respectively, P < .01). Patients in the lowest LVA4LS tertile (<13%) had significantly higher C-reactive protein and high-sensitivity troponin, need for intensive care, and need for mechanical life support as well as longer hospital length of stay compared with those in the highest tertile (>18.5%; P < .01). Initial LVA4LS and LVGLS were normal in 13 of 54 and 10 of 39 patients, respectively. There was no mortality. In multivariate regression, only LVA4LS was associated with both the need for intensive care and length of stay. At median 10-week follow-up to date, seven of 36 patients (19%) and six of 25 patients (24%) had abnormal LVA4LS and LVGLS, respectively. Initial LVA4LS < 16.2% indicated abnormal LVA4LS at follow-up with 100% sensitivity. CONCLUSION: Impaired LVGLS and LVA4LS at initial presentation independently indicate a higher risk for adverse acute clinical course and persistent subclinical left ventricular dysfunction at 10-week follow-up, suggesting that they could be applied to identify higher risk children with MIS-C.

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.