Faculty Bibliography

Importance/UNASSIGNED:Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective/UNASSIGNED:To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants/UNASSIGNED:Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures/UNASSIGNED:Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures/UNASSIGNED:Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results/UNASSIGNED:Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance/UNASSIGNED:In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

Importance/UNASSIGNED:Refinement of criteria for multisystem inflammatory syndrome in children (MIS-C) may inform efforts to improve health outcomes. Objective/UNASSIGNED:To compare clinical characteristics and outcomes of children and adolescents with MIS-C vs those with severe coronavirus disease 2019 (COVID-19). Setting, Design, and Participants/UNASSIGNED:Case series of 1116 patients aged younger than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Final date of follow-up was January 5, 2021. Patients with MIS-C had fever, inflammation, multisystem involvement, and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) or antibody test results or recent exposure with no alternate diagnosis. Patients with COVID-19 had positive RT-PCR test results and severe organ system involvement. Exposure/UNASSIGNED:SARS-CoV-2. Main Outcomes and Measures/UNASSIGNED:Presenting symptoms, organ system complications, laboratory biomarkers, interventions, and clinical outcomes. Multivariable regression was used to compute adjusted risk ratios (aRRs) of factors associated with MIS-C vs COVID-19. Results/UNASSIGNED:Of 1116 patients (median age, 9.7 years; 45% female), 539 (48%) were diagnosed with MIS-C and 577 (52%) with COVID-19. Compared with patients with COVID-19, patients with MIS-C were more likely to be 6 to 12 years old (40.8% vs 19.4%; absolute risk difference [RD], 21.4% [95% CI, 16.1%-26.7%]; aRR, 1.51 [95% CI, 1.33-1.72] vs 0-5 years) and non-Hispanic Black (32.3% vs 21.5%; RD, 10.8% [95% CI, 5.6%-16.0%]; aRR, 1.43 [95% CI, 1.17-1.76] vs White). Compared with patients with COVID-19, patients with MIS-C were more likely to have cardiorespiratory involvement (56.0% vs 8.8%; RD, 47.2% [95% CI, 42.4%-52.0%]; aRR, 2.99 [95% CI, 2.55-3.50] vs respiratory involvement), cardiovascular without respiratory involvement (10.6% vs 2.9%; RD, 7.7% [95% CI, 4.7%-10.6%]; aRR, 2.49 [95% CI, 2.05-3.02] vs respiratory involvement), and mucocutaneous without cardiorespiratory involvement (7.1% vs 2.3%; RD, 4.8% [95% CI, 2.3%-7.3%]; aRR, 2.29 [95% CI, 1.84-2.85] vs respiratory involvement). Patients with MIS-C had higher neutrophil to lymphocyte ratio (median, 6.4 vs 2.7, P < .001), higher C-reactive protein level (median, 152 mg/L vs 33 mg/L; P < .001), and lower platelet count (<150 ×103 cells/μL [212/523 {41%} vs 84/486 {17%}, P < .001]). A total of 398 patients (73.8%) with MIS-C and 253 (43.8%) with COVID-19 were admitted to the intensive care unit, and 10 (1.9%) with MIS-C and 8 (1.4%) with COVID-19 died during hospitalization. Among patients with MIS-C with reduced left ventricular systolic function (172/503, 34.2%) and coronary artery aneurysm (57/424, 13.4%), an estimated 91.0% (95% CI, 86.0%-94.7%) and 79.1% (95% CI, 67.1%-89.1%), respectively, normalized within 30 days. Conclusions and Relevance/UNASSIGNED:This case series of patients with MIS-C and with COVID-19 identified patterns of clinical presentation and organ system involvement. These patterns may help differentiate between MIS-C and COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) is thought to follow SARS-CoV-2 infection and presents with fever and multisystem dysfunction. We report three children with suspected MIS-C found to have retropharyngeal edema without evidence of a bacterial etiology. We raise the possibility that an association between MIS-C and retropharyngeal edema exists.

BACKGROUND:Outcomes in neonates receiving extracorporeal membrane oxygenation (ECMO) for meconium aspiration syndrome (MAS) and/or persistent pulmonary hypertension (PPHN) are favorable. Infants with preserved perfusion are often offered venovenous (VV) support to spare morbidities of venoarterial (VA) ECMO. Worsening perfusion or circuit complications can prompt conversion from VV-to-VA support. We examined whether outcomes in infants requiring VA ECMO for MAS/PPHN differed if they underwent VA support initially versus converting to VA after a VV trial, and what factors predicted conversion. METHODS:We reviewed the Extracorporeal Life Support Organization registry from 2007 to 2017 for neonates with primary diagnoses of MAS/PPHN. Propensity score analysis matched VA single-runs (controls) 4:1 against VV-to-VA conversions based on age, pre-ECMO pH, and precannulation arrests. Primary outcomes were complications and survival. Data were analyzed using Mann-Whitney U and Fisher's exact testing. Multivariate regression identified independent predictors of conversion for VV patients. RESULTS:3831 neonates underwent ECMO for MAS/PPHN, including 2129 (55%) initially requiring VA support. Of 1702 patients placed on VV ECMO, 98 (5.8%) required VV-to-VA conversion. Compared with 364 propensity-matched isolated VA controls, conversion runs were longer (190 vs. 127 h, P < 0.001), were associated with more complications, and decreased survival to discharge (70% vs. 83%, P = 0.01). On multivariate regression, conversion was more likely if neonates on VV ECMO did not receive surfactant (OR = 1.7;95%CI = 1.1-2.7;P = 0.03) or required high-frequency ventilation (OR = 1.9;95%CI = 1.2-3.3;P = 0.01) before ECMO. CONCLUSION/CONCLUSIONS:Conversion from VV-to-VA ECMO in infants with MAS/PPHN conveys increased morbidity and mortality compared to similar patients placed initially onto VA ECMO. VV patients not receiving surfactant or requiring high-frequency ventilation before cannulation may have increased risk of conversion. While conversions remain rare, decisions to offer VV ECMO for MAS/PPHN must be informed by inferior outcomes observed should conversion be required. LEVEL OF EVIDENCE/METHODS:Level of evidence 3 Retrospective comparative study.

INTRODUCTION: Multisystem Inflammatory Syndrome in Children (MIS-C) is a newly described inflammatory state that is thought to arise from immune dysregulation following SARS-CoV-2 infection. The Centers for Disease Control and Prevention criteria for diagnosis are: age less than 21-yearsold, fever, elevated inflammatory markers, multisystem organ involvement, absence of plausible alternative diagnosis, and current or prior SARS-CoV-2 infection. We report four patients with presumed MIS-C who were found to have retropharyngeal abscesses/fluid collections.
METHOD(S): The first is a 12-year-old male presenting with fevers, neck pain, rash, fluid-responsive shock, acute kidney injury, respiratory failure, and a CT scan showing a right-sided retropharyngeal abscess (0.8x3.0x6cm) with right cervical adenitis; he underwent incision and drainage of the retropharyngeal collection, which yielded no pus and grew S. parasanguinis. The second case is a 4-year-old male presenting with fevers, conjunctivitis, abdominal pain, sore throat, a negative rapid strep at urgent care, stridor, an elevated B-type natriuretic peptide, fluid-responsive shock, acute kidney injury, and a CT scan that showed a retropharyngeal effusion (1.5x0.6x5cm). The third case is a 13-year-old female presenting with fevers, cracked lips, sore throat, a negative throat culture, vasodilatory shock, a mildly dilated left main coronary artery, and a CT scan that showed a retropharyngeal abscess (0.7x2.9x7.8cm). The fourth case is a 6-month-old female presenting with fevers, an urticarial rash, lip redness, cervical lymphadenopathy, and a CT scan showing a right-sided retropharyngeal abscess (1.2x2.8x3.7cm) and right carotid arteritis; throat culture was not performed. All four patients had elevated inflammatory markers, SARS-CoV-2 IgG antibodies, and were treated with broad spectrum antibiotics. The first three patients received immunomodulatory treatment for presumed MIS-C.
RESULT(S): Based on these cases, we question whether an association between MIS-C and retropharyngeal fluid collections exists; epidemiological studies are warranted to investigate this possibility further. While the mechanism remains unclear, retropharyngeal fluid collections have been described in Kawasaki Disease, which is thought to share features with MIS-C

INTRODUCTION: A very small proportion of children who get infected with the novel coronavirus (COVID-19) have a severe disease requiring ICU care. Little is known about what risk factors are associated with severe disease in children. The purpose of this study was to compare characteristics of children with ?severe? disease defined as those requiring ICU admission vs. ?moderate? disease (hospital but not ICU admission) using the VIRUS: COVID 19 registry.
METHOD(S): Retrospective analysis of the Society of Critical Care Medicine VIRUS: COVID-19 registry encompassing children hospitalized at 49 participating sites between 02/20 to 07/20. Patient demographics and clinical presentations were compared among patients who required ICU admission vs. those who did not. Univariate and Multivariate logistic regression was performed using JMP.
RESULT(S): Data was available for 398 children, of which 181 (45.4%) were admitted to ICU. Children who required ICU admission were older (10 years vs. 3.67 years, p<0.01) and were more likely to be African American (28.8% versus 17.8%, p= 0.02). A higher proportion of patients who required ICU admission have pre-existing conditions (58.2% vs. 44.3%, p= 0.01). Asthma was the most common pre-existing condition; but, a higher proportion of ICU admits had a diagnosis of asthma (14.2% vs. 7.52%, p= 0.01). The most common presenting symptom was fever; however, this did not differ between groups. Nausea/vomiting (38.4% vs. 22.1%, p<0.01), dyspnea (31.8% vs 17.7%, p<0.01) and abdominal pain (25.2% vs. 14.1%, p<0.01) were more common in patients requiring ICU admission. A significantly higher proportion of patients who required ICU had multisystem inflammatory syndrome of childhood [MIS-C (45.9% vs. 6.8%, p<0.01)] and acute kidney injury (9.34% vs. 1.7%, p<0.01). Race (AA vs white, odds ratio 1.9, p = 0.02) and age (p <0.01) were associated with the risk of ICU admission on multi variate logistic regression. Presence of preexisting conditions was not significant after accounting for age and race (p=0.07).
CONCLUSION(S): Preliminary data suggest that children requiring ICU admissions for severe COVID-19 infections are more likely to be older and from African American race. Asthma is the most common preexisting condition. Gastrointestinal complains are more likely in severe COVID infections

INTRODUCTION: Coronavirus disease (COVID-19) has affected all age groups across the world. There is limited multi-center data on characteristics and outcomes of COVID-19 in hospitalized children. Using Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry - a large, multicenter, international database, we sought to describe the characteristics, pre-existing conditions, need for pediatric intensive care unit (PICU) admission and outcomes in children hospitalized with COVID-19.
METHOD(S): We conducted a retrospective review of data submitted to SCCM VIRUS database and included COVID-19 positive children hospitalized between February 2020 to July 2020. We collected data on demographics, symptoms and signs, pre-existing conditions, occurrence of MIS-C (multi-system inflammatory syndrome in children), need for PICU admission, hospital mortality and length of stay (LOS) among children hospitalized with COVID-19. We reported findings using descriptive analysis with median and interquartile range (IQR).
RESULT(S): A total 419 children (<18 years) were admitted to 49 participating hospitals due to COVID-19. The median age was 7 (1-15) years (N=413) and male: female ratio was 1.2:1. A majority were White (48%), followed by African American (23%) and other race (22%) (out of N=412). The ethnic distribution consisted of 52% Non-Hispanic, 39% Hispanic and 9% unknown (out of N=410). The median (IQR) weight was 27 (9-64.5) kgs (out of N=407) and height was 120 (67-161) cm (out of N=377). A majority of children presented with fever (61%), followed by nausea/vomiting (29%), dry cough (24%) and abdominal pain (19%). Half (51%) of children had pre-existing conditions (out of N=336), 28% children had CDC criteria of MIS-C (out of N=365) and 45% children needed PICU care (out of N=402). The hospital mortality was 3.5% (out of N=313) and LOS [median (IQR)] was 4 (1.8-8.1) days (N=313) with majority (93%) children discharged to home without assistance (out of N=296).
CONCLUSION(S): This report describes the characteristics and outcomes of children hospitalized with COVID-19 from one of the largest COVID-19 global database. Though a good proportion of children hospitalized with COVID-19 had pre-existing conditions and needed PICU care, overall hospital mortality was low

Since March 2015, our Pediatric ECMO team has cared for 31 patients. Of these, 16 patients are still living today (53%). Patient & family support are necessary during ECMO, as well as post-ECMO and hospital discharge. Recent studies show that not only patients who required ECMO fulfill post-traumatic stress disorder diagnostic criteria, but also their close relatives are at risk to develop PTSD. Minimal peer to peer resources exist in the community for these patients and families. We found this to be a gap in ECMO care and an area of opportunity for us to provide additional support to this patient population. Our team explored options for engaging and decided to host our first Pediatric ECMO Reunion. The reunion included both patients & families and multidisciplinary staff members who cared for our prior ECMO patients. This venue provided an opportunity for sharing patient stories, for ECMO providers to reconnect with survivors and staff to experience the positive outcomes from their work. This allowed for a first step for families to understand their experience and help decrease burnout in providers and staff. We provided families the option to stay in touch with the ECMO Program through different family work groups. We also interviewed families and distributed surveys for direct feedback on their experience working with our team while their child was on ECMO. Next steps include creating an ECMO Family Work Group by partnering with families to develop new ways to support future ECMO families and improve the ECMO family experience

The majority of neonatal and pediatric patients require emergent cannulations at the bedside in the intensive care unit (ICU). To accomplish a bedside cannulation, multidisciplinary teams need to work together and perform tasks that may be different from the usual practices in the ICU. The complexity of the many tasks that need to be completed can lead to significant delay if not well choreographed. Our project goal was to streamline the pre-cannulation process to decrease the time from ECMO mobilization to procedure start. The initiative was implemented in September 2016. Interventions included formalization of ECMO Program policies & procedures and multidisciplinary education, as well as implementation of formal patient case reviews & quality assurance meetings. Our team collaborated with ancillary departments to ensure timeliness and efficiency with orders & processes related to ECMO initiation. We also created a detailed precannulation checklist which defines each team members' role and their responsibilities in the pre-cannulation process. The checklist is reviewed prior to the procedure time out as a final check to ensure all required tasks are completed. Upon retrospective chart review, the pre- & post-initiative data revealed a 54% decrease in time from ECMO mobilization to cannulation procedure start. The post-initiative average time of 65 minutes showed successful improvement from the pre-initiative average time of 136 minutes. We concluded that a structured process for pre-cannulation preparedness, role definition, multidisciplinary education, and team debriefs maximize efficiency in team readiness for a bedside ECMO cannulation procedure