Epidemiology and Clinical Features of Human Metapneumovirus and Respiratory Syncytial Viral Infections in Children.

BACKGROUND: Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are 2 common causes of acute respiratory tract infections in infants and young children. The objective of this study is to compare the demographics and outcomes of children hospitalized with HMPV and RSV infections in the United States. METHODS: We performed a retrospective cohort analysis of children 1 month to less than 3 years old discharged during 2016 with HMPV or RSV infection using the Kids' Inpatient Database. Children with HMPV and RSV coinfection were excluded. Data were weighted for national estimates. RESULTS: There were 6585 children with HMPV infection and 70,824 with RSV infection discharged during the study period. The mean age of children with HMPV infection was higher than that of children with RSV infection (0.73 ± 0.8 vs. 0.42 ± 0.7 years; P < 0.05). The mortality rate was significantly higher in children with the presence of any complex chronic conditions compared to those without, in both HMPV [odds ratio (OR): 32.42; CI: 9.931-105.857; P < 0.05] as well as RSV (OR: 35.81; CI: 21.12-57.97; P < 0.05) groups. The adjusted median length of stay was longer (4.64 days; CI: 4.52-4.76 days vs. 3.33 days; CI: 3.31-3.35 days; P < 0.001) and total charges were higher ($44,358; CI: $42,145-$46,570 vs. $22,839; CI: $22,512-$23,166; P < 0.001), with HMPV infection. The mortality rate was similar in HMPV infection compared to RSV infection on multivariable analysis (OR: 1.48; P > 0.05). CONCLUSION: In hospitalized children in the United States, HMPV infection is less common than RSV infection. Complex chronic conditions are more prevalent in children hospitalized with HMPV infection. Hospitalization with HMPV is associated with longer length of stay and higher hospital charges. The adjusted mortality is similar with both infections.

Identification of Multisystem Inflammatory Syndrome in Children Classes and Development of Hyperinflammation Score in Pediatric COVID-19.

The aim of this study is to describe characteristics and hospital course of children admitted with COVID-19 to a tertiary care pediatric center in Southeastern United States, and to present the frequency of three classes of multisystem inflammatory syndrome in children (MIS-C) and develop pediatric COVID-19 associated hyperinflammation score (PcHIS). A retrospective cohort study of 68 children was performed. Critical illness was defined as any child requiring respiratory or cardiovascular support or renal replacement therapy. PcHIS was developed by using six variables: fever, hematological dysfunction, coagulopathy, hepatic injury, macrophage activation, and cytokinemia. Centers for Disease Control and Prevention criteria were used to identify MIS-C, and three classes of MIS-C were identified based on the findings of recently published latent class analysis (Class 1: MIS-C without Kawasaki like disease, Class 2: MIS-C with respiratory disease, and Class 3: MIS-C with Kawasaki like disease). The median age was 6.4 years. Fever, respiratory, and gastrointestinal were common presenting symptoms. MIS-C was present in 32 (47%), critical COVID-19 illness in 11 (16%), and 17 (25%) were admitted to the PICU. Children with critical illness were adolescents with elevated body mass index and premorbid conditions. PcHIS score of 3 had a sensitivity of 100% and a specificity of 77% for predicting critical COVID-19 illness. Among MIS-C patients, 15 (47%) were in Class 1, 8 (25%) were in Class 2, and 9 (28%) were in Class 3. We conclude that most children with COVID-19 have mild-to-moderate illness. Critical COVID-19 is mainly seen in obese adolescents with premorbid conditions. Three Classes of MIS-C are identifiable based on clinical features. Validation and clinical implication of inflammation score in pediatric COVID-19 need further investigation.

Coronavirus Disease 2019 in Pediatric Oncology Patients: A Matched-Cohort Analysis of the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry.

BACKGROUND: There is a paucity of multicenter data describing the impact of coronavirus disease 2019 (COVID-19) on hospitalized pediatric oncology patients. Using a large, multicenter, Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness University Study (VIRUS) database, we aimed at assessing outcomes of COVID-19 infection in this population. METHOD: This is a matched-cohort study involving children below 18 years of age hospitalized with COVID-19 between March 2020 and January 2021. Using the VIRUS; COVID-19 Registry database, children with oncologic diseases were compared with propensity score matched (age groups, sex, race, and ethnicity) cohort of children without oncologic diseases for the prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C), intensive care unit (ICU) admission, interventions, hospital, and ICU length of stay. RESULTS: The number of children in the case and control groups was 45 and 180, respectively. ICU admission rate was similar in both groups ([47.7 vs 51.7%], P =0.63). The proportion of children requiring noninvasive and invasive mechanical ventilation, and its duration were similar between groups, same as hospital mortality. Interestingly, MIS-C was significantly lower in the oncology group compared with the control (2.4 vs 24.6%; P =0.0002). CONCLUSIONS: In this study using a multicenter VIRUS database, ICU admission rate, interventions, and outcomes of COVID-19 were similar in children with the oncologic disease compared with control patients. The incidence of MIS-C is lower in oncologic patients.

Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children.

Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence. Design, Setting, and Participants: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry. Exposure: Administration of steroids within 2 days of admission. Main Outcomes and Measures: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. Results: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators. Conclusions and Relevance: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

Pediatric Cardiac Arrest Outcomes in the United States: A Nationwide Database Cohort Study.

Background Knowledge about the causes and outcomes of pediatric cardiac arrest in the emergency department is limited. The aim of our study was to evaluate the characteristics and outcomes of pediatric cardiac arrest in the emergency department (EDCA) and inpatient (IPCA) settings in the United States using a large database designed to provide nationwide estimates. Methods We performed a retrospective cohort study using the Nationwide Emergency Department Sample (NEDS), a database that includes both ED and inpatient encounters. The NEDS was analyzed for episodes of cardiac arrest between 2016-2018 in patients aged ≤18 years. Patients with cardiac arrest were identified using the International Classification of Diseases, 10th revision codes. Results A total of 15,348 pediatric cardiac arrest events with cardiopulmonary resuscitation were recorded, of which 13,239 had EDCA and 2,109 had IPCA. A lower survival rate of 19% was observed for EDCA compared to 40.4% for IPCA. While more than half of the EDCA events had no associated diagnoses, trauma (15.6%), respiratory failure (5%), asphyxiation (2.7%), acidosis (2.4%), and ventricular arrhythmia (1.4%) were associated with the remaining events. In comparison, the most frequently associated diagnoses for IPCA were respiratory failure (75.8%), acidosis (43.9%), acute kidney injury (27.2%), trauma (27.1%), and sepsis (22.5%).  Conclusions Survival rates for EDCA were less than half of that for IPCA. The low survival rates along with the distinctive characteristics of EDCA events suggest the need for further research in this area to identify remediable factors and improve survival.

Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19: A retrospective cohort analysis from 28 U.S. Hospitals.

OBJECTIVES: Suggested therapeutic options for Multisystem Inflammatory Syndrome in Children (MIS-C) include intravenous immunoglobulins (IVIG) and steroids. Prior studies have shown the benefit of combination therapy with both agents on fever control or the resolution of organ dysfunction. The primary objective of this study was to analyze the impact of IVIG and steroids on hospital and ICU length of stay (LOS) in patients with MIS-C associated with Coronavirus Disease 2019 (COVID-19). STUDY DESIGN: This was a retrospective study on 356 hospitalized patients with MIS-C from March 2020 to September 2021 (28 sites in the United States) in the Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry. The effect of IVIG and steroids initiated in the first 2 days of admission, alone or in combination, on LOS was analyzed. Adjustment for confounders was made by multivariable mixed regression with a random intercept for the site. RESULTS: The median age of the study population was 8.8 (Interquartile range (IQR) 4.0, 13) years. 247/356 (69%) patients required intensive care unit (ICU) admission during hospitalization. Overall hospital mortality was 2% (7/356). Of the total patients, 153 (43%) received IVIG and steroids, 33 (9%) received IVIG only, 43 (12%) received steroids only, and 127 (36%) received neither within 2 days of admission. After adjustment of confounders, only combination therapy showed a significant decrease of ICU LOS by 1.6 days compared to no therapy (exponentiated coefficient 0.71 [95% confidence interval 0.51, 0.97, p = 0.03]). No significant difference was observed in hospital LOS or the secondary outcome variable of the normalization of inflammatory mediators by Day 3. CONCLUSIONS: Combination therapy with IVIG and steroids initiated in the first 2 days of admission favorably impacts ICU but not the overall hospital LOS in children with MIS-C.

Pediatric COVID-19 presenting as supraglottitis with vocal cord hypomobility.

In the United States, an estimated 7.3% of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) are among persons aged less than 18 years. Data regarding clinical manifestations in this age group are still evolving. An upper airway predilection has been reported in children. We describe the case of a 15-year-old female with supraglottitis and unilateral hypomobility of vocal cord with concern for critical airway, associated with COVID-19. She was managed by a multidisciplinary team including critical care, infectious diseases, and otolaryngology. This report adds to the sparse but evolving body of literature on the clinical presentation of COVID-19 disease in children.