ABSTRACT
INTRODUCTION: Interest in using bedside C-reactive protein and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies piqued with the COVID-19 pandemic experience. These widely available low-cost biomarkers might be similarly useful for assessing inflammatory profiles of all critically ill children with sepsis and septic shock and eventually guiding the use of precision anti-inflammatory therapies. We hypothesized groupbased trajectories of CRP and ferritin among critically ill children with sepsis would be associated with mortality and distinct inflammatory cytokine profiles. METHODS: Children with sepsis and organ failure from 9 pediatric intensive care units were enrolled in a prospective, observational cohort. Plasma CRP (mg/dL), ferritin (ng/mL), and 29 cytokine levels were measured at two samplings during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin. RESULTS: Two hundred and fifty-five children had at least 2 CRP and ferritin measurements. Five distinct clinical multitrajectory groups were identified with significantly different median maximum organ failures (MOF) and mortality. Group 1 had normal CRP and ferritin levels (n = 8;median MOF 2.0 [interquartile range 1.0, 2.0] and 0 % mortality);Group 2 had high CRP levels that became normal, with normal ferritin levels throughout (n = 80;median MOF 2.0 [1.0, 2.0] and 5% mortality);Group 3 had high ferritin levels alone (n=16;median MOF 2.5 [2.0, 3.0] and 6.3% mortality);Group 4 had very high CRP levels, and increased ferritin levels (n = 121;median MOF 2.0 [2.0, 4.0] and 10.7% mortality);and, Group 5 had very high CRP and very high ferritin levels (n = 30;median MOF 3.0 [2.0, 4.0] and 40% mortality). Cytokine responses differed across the 5 groups, with ferritin levels associated with macrophage inflammatory protein 1 a, and CRP levels reflective of many cytokines. CONCLUSIONS: Bedside CRP and ferritin levels can be used together to compute distinct groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks potentially targetable in clinical trials evaluating specific anti-inflammatory therapies.
ABSTRACT
Background: Children and young adults were initially reported as largely spared from severe complications of SARS-CoV-2 infection, but the impact to this population has been significant. Methods: This observational retrospective cohort study includes 420 symptomatic children and young adults with lab confirmed SARS-CoV-2 infection treated between March 15 and June 16, 2020 at Children's National Hospital in Washington DC. We identified and compared cohorts of non-hospitalized (N=324) and hospitalized (N=96) patients, including non-critically ill (N=64) and critically ill hospitalized (N=32) patients. Clinical and demographic data were extracted from medical records Results: Of 420 SARS-CoV-2-infected symptomatic patients, 23% required hospitalization, of which 67% were non-critically ill and 33% were critically ill. All age groups were represented in the symptomatic cohort, with a median age of 8.6 years. Patients > 15 years of age represented 44% of critical care admissions. Males and females were equally represented in all cohorts. Underlying medical conditions were present in 36%, but more common in hospitalized (59 %) and critically ill (66 %) patients. The most frequent underlying diagnosis overall was asthma (16 %), but also included neurologic (6 %), diabetes (3 %), obesity (3 %), cardiac (3 %), hematologic (3 %) and oncologic (1 %) conditions. The majority (66 %) of SARSCoV- 2 infected patients presented with respiratory symptoms with or without fever. Other symptoms were also present, including diarrhea/vomiting (21 %), myalgia (11 %), chest pain (8 %) and loss of sense of smell or taste (7%). Hospitalized patients required varying levels of respiratory support, including mechanical ventilation, BiPAP, RAM cannula and HFNC. Additional presentations included diabetic hyperglycemia, sickle cell vaso-occlusive crisis, vascular complications, and multisystem inflammation. Treatment included remdesivir, convalescent plasma, tocilizumab and other therapies. Conclusion: Although children/young adults have been less affected than elderly adults, the impact of SARS-CoV2 on this population has been significant in Washington DC and informs other regions anticipating their surge.
ABSTRACT
Background: Background: Multi-system Inflammatory Syndrome of Children (MIS-C) has recently emerged internationally as a serious inflammatory complication of SARS-CoV-2 infection with significant morbidity for the pediatric population. Methods: This observational retrospective cohort study includes 33 children meeting CDC criteria for MIS-C treated between March 15 and June 17, 2020 at Children's National Hospital in Washington DC. Clinical and demographic data were extracted from medical records and are summarized. Results: Of 33 hospitalized MIS-C patients, 42% were critically ill, and 58% were non-critically ill. The median age was 8.9 years (0.7-18.7 years). More males (58 %) than females (43 %) were represented in the MIS-C cohort. The majority (75%) of children had no underlying medical condition. Criteria for incomplete or complete Kawasaki Disease (KD) were present in 39% of patients, while an additional 9% had some features of KD. However the remaining 52% of MIS-C patients presented with other sub-phenotypes including prominent severe abdominal pain and/or nonspecific multiorgan dysfunction. 30% presented with shock requiring volume and/or inotropic support. SARS-CoV-2 antibodies were present in 61% of patients. Virus was detectable by PCR in 36% of patients. At the time of initial evaluation, 39% (13/33) of children had identified cardiac abnormalities including myocardial dysfunction (5/33;15%), coronary ectasia (4/33;12%), coronary aneurysm (3/33;9%), or pericardial effusion 5/33;15%) either alone or in combination. Cytokine profiling identified elevation of several cytokines in this cohort, including IL-6. Treatment has included intravenous immunoglobulin, aspirin, anakinra and other immunomodulatory therapies, with overall rapid response to therapy. No deaths have occurred. Conclusion: The emergence of MIS-C late in the surge of SARS-CoV-2 circulation in the Washington DC metropolitan region has added to the already significant burden of hospitalized and critically ill children in our region. A significant percentage of these children present with cardiac dysfunction and abnormalities, whether or not with KD features at presentation. Detailed characterization of immune responses and long term outcome of these patients is a priority.