Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children
Importance/UNASSIGNED:There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). Objective/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:Administration of steroids within 2 days of admission. Main Outcomes and Measures/UNASSIGNED:Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. Results/UNASSIGNED: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; Pâ€‰=â€‰.42). Separate analyses for patients with an LOS of 2 days or longer (nâ€‰=â€‰729), those receiving respiratory support at admission (nâ€‰=â€‰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/UNASSIGNED: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.
Gastrointestinal Manifestations in Hospitalized Children With Acute SARS-CoV-2 Infection and Multisystem Inflammatory Condition: An Analysis of the VIRUS COVID-19 Registry
BACKGROUND:Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C). METHODS:Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality. RESULTS:Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes. CONCLUSIONS:GI involvement is common in hospitalized children with acute COVID-19 and MIS-C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C.
A Description of COVID-19-Directed Therapy in Children Admitted to US Intensive Care Units 2020
BACKGROUND:It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. METHODS:Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. RESULTS:Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). CONCLUSION/CONCLUSIONS:Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies.
Continuing Care For Critically Ill Children Beyond Hospital Discharge: Current State of Follow-up
OBJECTIVES/OBJECTIVE:Survivors of the PICU face long-term morbidities across health domains. In this study, we detail active PICU follow-up programs (PFUPs) and identify perceptions and barriers about development and maintenance of PFUPs. METHODS:A web link to an adaptive survey was distributed through organizational listservs. Descriptive statistics characterized the sample and details of existing PFUPs. Likert responses regarding benefits and barriers were summarized. RESULTS:One hundred eleven respondents represented 60 institutions located in the United States (n = 55), Canada (n = 3), Australia (n = 1), and the United Kingdom (n = 1). Details for 17 active programs were provided. Five programs included broad PICU populations, while the majority were neurocritical care (53%) focused. Despite strong agreement on the need to assess and treat morbidity across multiple health domains, 29% were physician only programs, and considerable variation existed in services provided by programs across settings. More than 80% of all respondents agreed PFUPs provide direct benefits and are essential to advancing knowledge on long-term PICU outcomes. Respondents identified "lack of support" as the most important barrier, particularly funding for providers and staff, and lack of clinical space, though successful programs overcome this challenge using a variety of funding resources. CONCLUSIONS:Few systematic multidisciplinary PFUPs exist despite strong agreement about importance of this care and direct benefit to patients and families. We recommend stakeholders use our description of successful programs as a framework to develop multidisciplinary models to elevate continuity across inpatient and outpatient settings, improve patient care, and foster collaboration to advance knowledge.
Frequency, Characteristics and Complications of COVID-19 in Hospitalized Infants
BACKGROUND:Previous studies of severe acute respiratory syndrome coronavirus 2 infection in infants have incompletely characterized factors associated with severe illness or focused on infants born to mothers with coronavirus disease 2019 (COVID-19). Here we highlight demographics, clinical characteristics and laboratory values that differ between infants with and without severe acute COVID-19. METHODS:Active surveillance was performed by the Overcoming COVID-19 network to identify children and adolescents with severe acute respiratory syndrome coronavirus 2-related illness hospitalized at 62 sites in 31 states from March 15 to December 27, 2020. We analyzed patients aged >7 days to <1 year hospitalized with symptomatic acute COVID-19. RESULTS:We report 232 infants aged >7 days to <1 year hospitalized with acute symptomatic COVID-19 from 37 US hospitals in our cohort from March 15 to December 27, 2020. Among 630 cases of severe COVID-19 in patients aged >7 days to <18 years, 128 (20.3%) were infants. In infants with severe illness from the entire study period, the median age was 2 months, 66% were from racial and ethnic minority groups, 66% were previously healthy, 73% had respiratory complications, 13% received mechanical ventilation and <1% died. CONCLUSIONS:Infants accounted for over a fifth of children aged <18 years hospitalized for severe acute COVID-19, commonly manifesting with respiratory symptoms and complications. Although most infants hospitalized with COVID-19 did not suffer significant complications, longer term outcomes remain unclear. Notably, 75% of infants with severe disease were <6 months of age in this cohort study period, which predated maternal COVID-19 vaccination, underscoring the importance of maternal vaccination for COVID-19 in protecting the mother and infant.
Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry
OBJECTIVES:Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry. DESIGN:Retrospective study. SETTING:Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry. PATIENTS:Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4â€‰kg/m2 (16-25.8â€‰kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased. CONCLUSIONS:In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.
Racial-ethnic disparities in outcomes of children hospitalized for COVID-19: A virus registry report [Meeting Abstract]
INTRODUCTION: Adult racial and ethnic minorities in the U.S. with COVID-19 are known to have worse outcomes. The CDC reported higher incidence of COVID-19 among minority children, but data regarding disparities in pediatric COVID-19 outcomes remains limited.
METHOD(S): A total of 837 children < 18 years of age hospitalized with COVID-19 in the U.S. were entered into the SCCM VIRUS Registry from 03/2020 to 01/2021. They were grouped into either of the following: Hispanic, non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Other or Unknown. Demographic and clinical characteristics, interventions and outcomes were compared. Critical illness was defined using a composite index of in-hospital mortality and organ support requirement, including vasopressors/inotropes, ECMO and CRRT. Comparisons were made using ANOVA, Kruskal-Wallis or Pearson's Chi-square. We used multivariable logistic and linear regression analysis to examine associations between race and ethnicity and critical illness, hospital and ICU length of stay and hospital mortality.
RESULT(S): Fever was reported in 67%, with no difference among the groups. MIS-C was reported with a significantly higher proportion in non-Hispanic Blacks (36%) than in non- Hispanic Whites (26%) [p=0.02]. Adjusting for age, sex, obesity, immune compromise and asthma, the non-Hispanic Asian group was significantly associated with higher odds of critical illness [OR=5.83, 95% CI=2.13-15.81]. Non-Hispanic Blacks also had higher odds of critical illness than non-Hispanic Whites, though not significant [OR=1.59, 95% CI=0.99-2.54]. With each yearly increase in age, the odds of critical illness was higher [OR=1.04, 95% CI=0.99-1.07] given all other covariates remain the same. While there was a higher proportion of obesity in the Hispanic group, this did not increase their odds of critical illness. Non- Hispanic Blacks had longer hospital length of stay compared to non-Hispanic Whites, though not significant [OR=1.76, 95% CI=-0.17-3.68]. ICU length of stay and mortality were not significantly associated with race or ethnicity.
CONCLUSION(S): Racial and ethnic disparities in pediatric COVID-19 outcomes exist that are not associated with preexisting conditions. These findings may guide the allocation of critical care resources towards minority groups at higher risk for severe disease
Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C
BACKGROUND:Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS:Multicenter, cross-sectional study of neurological manifestations in children aged <18Â years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS:Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both PÂ <Â 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), PÂ <Â 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all PÂ <Â 0.05. CONCLUSIONS:In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.
The Impact of Obesity on Disease Severity and Outcomes Among Hospitalized Children With COVID-19
OBJECTIVE:To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children. METHODS:This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay. RESULTS:= .38). CONCLUSION:In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness.
Data-driven clustering identifies features distinguishing multisystem inflammatory syndrome from acute COVID-19 in children and adolescents
Background/UNASSIGNED:Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia. Methods/UNASSIGNED:We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients. Findings/UNASSIGNED:Â =Â 583; 19% labeled MIS-C) were younger (2Â·8Â Â±Â 2Â·0 y), PCR positive (86%), with less inflammation. Radiographic findings of pulmonary infiltrates and positive SARS-CoV-2 PCR accurately distinguished cluster 2 MIS-C labeled patients from cluster 1 patients. Interpretation/UNASSIGNED:Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C may be misclassified. These data driven phenotypes may help refine the diagnosis of MIS-C.