A 10-year-old previously healthy boy presented to the emergency department with 6 days of persistent fever; 4 days of abdominal pain, emesis and diarrhea; and bilateral nonpurulent conjunctivitis and ...red cracked lips. Four weeks before presentation, the patient had had 3 days of headache with no respiratory symptoms, and he and his family had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nasopharyngeal swab. On arrival at the emergency department, his blood pressure was 74/35 mm Hg and heart rate was 130 beats/min despite 60 mL/kg of fluid resuscitation. He was cool and had poor perfusion. He received inotrope support and empiric antibiotics and was transferred to the intensive care unit (ICU). A rigorous scientific approach to data collection and analysis using internationally harmonized definitions is needed to improve our understanding of this emerging syndrome and to help guide clinical decision-making. The CPS, in collaboration with the Public Health Agency of Canada, has expanded its active surveillance in COVID-19 to include cases of pediatric inflammatory multisystem syndrome or Kawasaki disease at a national level.
SARS-CoV-2 infection can lead to multisystem inflammatory syndrome in children (MIS-C). We sought to investigate risk factors for admission to the intensive care unit (ICU) and explored changes in ...disease severity over time.
We obtained data from chart reviews of children younger than 18 years with confirmed or probable MIS-C who were admitted to 15 hospitals in Canada, Iran and Costa Rica between Mar. 1, 2020, and Mar. 7, 2021. Using multivariable analyses, we evaluated whether admission date and other characteristics were associated with ICU admission or cardiac involvement.
Of 232 children with MIS-C (median age 5.8 yr), 130 (56.0%) were male and 50 (21.6%) had comorbidities. Seventy-three (31.5%) patients were admitted to the ICU but none died. We observed an increased risk of ICU admission among children aged 13-17 years (adjusted risk difference 27.7%, 95% confidence interval CI 8.3% to 47.2%), those aged 6-12 years (adjusted risk difference 25.2%, 95% CI 13.6% to 36.9%) or those with initial ferritin levels greater than 500 μg/L (adjusted risk difference 18.4%, 95% CI 5.6% to 31.3%). Children admitted to hospital after Oct. 31, 2020, had numerically higher rates of ICU admission (adjusted risk difference 12.3%, 95% CI -0.3% to 25.0%) and significantly higher rates of cardiac involvement (adjusted risk difference 30.9%, 95% CI 17.3% to 44.4%). At Canadian sites, the risk of ICU admission was significantly higher for children admitted to hospital between December 2020 and March 2021 than those admitted between March and May 2020 (adjusted risk difference 25.3%, 95% CI 6.5% to 44.0%).
We observed that age and higher ferritin levels were associated with more severe MIS-C. We observed greater severity of MIS-C later in the study period. Whether emerging SARS-CoV-2 variants pose different risks of severe MIS-C needs to be determined.
Introduction
Coagulopathy and thrombosis associated with SARS‐CoV‐2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited.
Methods
An ...international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS‐CoV‐2 and multisystem inflammatory syndrome (MIS‐C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub‐study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes.
Results
Nine hundred eighty‐five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS‐CoV‐2 infection, 288 had MIS‐C (31.4%), and 242 (26.4%) had SARS‐CoV‐2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p‐value .007), respiratory support (p‐value .006), central venous catheter (CVC) (p = .04) in children with primary SARS‐CoV‐2 and in those with MIS‐C included respiratory support (p‐value .03), obesity (p‐value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS‐CoV‐2 infection and in those with MIS‐C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage.
Conclusion
Thrombosis and hemorrhage are uncommon events in children with SARS‐CoV‐2; largely experienced by those with pre‐existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS‐CoV‐2 infection requires ongoing research.
Childhood-onset Systemic Lupus Erythematosus (cSLE) is an autoimmune disease associated with fatigue, mood symptoms, and pain. Fortunately, these symptoms are potentially modifiable with ...psychological intervention such as cognitive-behavioral therapy (CBT). The Treatment and Education Approach for Childhood-onset Lupus (TEACH) program is a CBT intervention developed to target these symptoms for adolescents and young adults with cSLE. This pilot randomized controlled trial (RCT) aims to determine the feasibility and effect of TEACH for youth with cSLE. Adjustments to the study protocol following the COVID-19 pandemic are also described.
This two-arm multisite RCT will explore the feasibility (primary outcome) and effect (secondary outcome) of a remotely delivered TEACH protocol. Participants will be randomized to a six-week remotely delivered TEACH program plus medical treatment as usual (TAU) or TAU alone. We will include patients ages 12-22 years presenting to rheumatology clinics from six sites. Validated measures of fatigue, depressive symptoms, and pain will be obtained at baseline and approximately eight and 20 weeks later. Protocol adjustments were also made due to the COVID-19 pandemic, in collaboration with the investigative team, which included patients and caregivers.
Findings from this multi-site RCT aim to document the feasibility of TEACH and provide an estimate of effect of a remotely delivered TEACH protocol on fatigue, depression, and pain symptoms in youth with cSLE as compared to standard medical treatment alone. This findings may positively impact clinical care for patients with cSLE.
gov registration: NCT04335643.
Purpose
The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection.
Methods
Seventeen pediatric ...hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome.
Results
Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home.
Conclusion
Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.
Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of ...this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2.
This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement.
One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (
= 103), encephalopathy (
= 28), and seizures (
= 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55;
= 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59;
< 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15;
< 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40;
< 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42;
= 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97,
= 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82;
< 0.001).
In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.
Several common degenerative mechanisms and mediators underlying the neuronal injury pathways characterize several neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's ...disease, as well as brain neurotrauma. Such common ground invites the emergence of new approaches and tools to study the altered pathways involved in neural injury alongside with neuritogenesis, an intricate process that commences with neuronal differentiation. Achieving a greater understanding of the impaired pathways of neuritogenesis would significantly help in uncovering detailed mechanisms of axonal regeneration. Among the several agents involved in neuritogenesis are the Rho and Rho kinases (ROCKs), which constitute key integral points in the Rho/ROCK pathway that is known to be disrupted in multiple neuropathologies such as spinal cord injury, traumatic brain injury, and Alzheimer's disease. This in turn renders ROCK inhibition as a promising candidate for therapeutic targets for treatment of neurodegenerative diseases. Among the novel tools to investigate the mechanisms involved in a specific disorder is the use of neuroproteomics/systems biology approach, a growing subfield of bioinformatics aiming to study and establishing a global assessment of the entire neuronal proteome, addressing the dynamic protein changes and interactions. This review aims to examine recent updates regarding how neuroproteomics aids in the understanding of molecular mechanisms of activation and inhibition in the area of neurogenesis and how Rho/ROCK pathway/ROCK inhibitors, primarily Y‐27632 and Fasudil compounds, are applied in biological settings, promoting neuronal survival and neuroprotection that has direct future implications in neurotrauma.
ObjectivesEmotional dysfunction in childhood-onset systemic lupus erythematosus (cSLE) impacts clinical outcomes and quality of life, but the relationship to lupus brain inflammation is poorly ...understood. We aimed to investigate the structural neural metrics and disease activity measures that predict anxiety and depression in cSLE and non-cSLE children.MethodsA cross-sectional sample of patients with cSLE (meeting ACR and/or SLICC classification criteria for SLE) and healthy controls, aged 10-17 years completed self-reported measures of depression (Beck Depression Inventory-II/Children’s Depression Inventory-2) and anxiety (Screen for Child Anxiety Related Disorders). Elevated depression/anxiety symptoms were determined by established clinical cut-offs. T1-weighted sequences were acquired on a 3T Siemens MRI. MRI scans were spatially normalized using the MNI-152 template, and grey and white matter were segmented to estimate brain volume, surface area and cortical thickness in Freesurfer. Measures of disease duration, activity (SLE Disease Activity Index (SLEDAI) 2000), glucocorticoid use and inflammation were collected. Partial least squares (PLS) analyses were used to investigate the association between structural brain metrics and disease measures with depression/anxiety symptom severity.ResultsTwenty-seven patients with cSLE (mean age=15.4 years (SD 1.7) and median SLEDAI=2.0 (IQR 2-4)) and 14 healthy controls were recruited. There were no group differences in age, sex or ethnicity. Median cumulative glucocorticoid use in this sample was 3.2 grams prednisone-equivalent (IQR 0.7- 11.2). One cSLE patient had a history of neuropsychiatric lupus. We did not find group differences in prevalence of clinically elevated depression (cSLE= 12/27, controls=6/14) or anxiety (cSLE= 11/27, controls=7/14). Within group analysis of brain MRI showed that for both cSLE patients and controls, worse mood and anxiety were both predicted by reduced right anterior cingulate thickness. Within the cSLE group, worse mood and anxiety was predicted by higher cumulative steroid use, reduced right fusiform gyrus cortical thickness, and increased left amygdala and right parahippocampal volumes and thickness.ConclusionThis cross-sectional sample of cSLE patients had mild disease activity at the time of the study, and a high but similar prevalence of emotion problems compared to controls. Worse emotional functioning was associated with altered structural changes in regions known to underlie emotion processing in both groups. Emotion difficulties in the cSLE group were related to cumulative glucocorticoid use, but not disease activity or inflammatory markers. Further research is needed to examine the role of glucocorticoid exposure in the setting of psychological stress related to having a chronic illness during the adolescent neurodevelopmental period.Lay SummaryChildren with lupus often experience problems with mood, such as depression and anxiety. These problems may be due to the effects of lupus on the brain, but the cause is currently unclear. We measured symptoms of depression and anxiety in 30 children with lupus. We also used advanced brain imaging to study changes in brain structure. We compared these measures between children with lupus and a group of 14 health peers. We also looked at how mood problems are related to brain imaging changes and lupus disease markers. Compared to their peers, we found that children with lupus had similar rates of depression and anxiety symptoms. We found that these symptoms were related to changes in brain structure in both children and their peers. In children with lupus, the symptoms were related to changes in particular brain areas. Depression and anxiety were also related to higher steroid use. These findings indicate that depression and anxiety symptoms are common in children with lupus and their peers. The results also suggest that these mood problems correlate with changes in the brain, and with steroid treatment for lupus. More research is needed to understand how steroid treatment impacts brain and mental health in children with lupus. This will lead to better mental health and overall care for these children.
ObjectiveTo identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection.DesignMulticentre retrospective cohort study.Setting18 hospitals in Canada, Iran and Costa Rica ...from 1 February 2020 to 31 May 2021.PatientsChildren<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C).Main outcome measureSeverity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses.ResultsWe identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53–10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45–9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease.ConclusionWe identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.
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