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1.
Front Pediatr ; 9: 707650, 2021.
Article in English | MEDLINE | ID: covidwho-1497112

ABSTRACT

Background: It has been suggested that children and infants can develop multisystem inflammatory syndrome in children (MIS-C) in response to a SARS-CoV-2 infection and that Black children are overrepresented among cases. The aim of the current study was to quantify the association between Black, Asian, or other non-White genetic background and COVID-19-related MIS-C in children and infants. Methods: Eight different research groups contributed cases of MIS-C, potentially related to SARS-CoV-2 infection. Several sensitivity analyses were performed, including additional data available from the literature. Analyses were stratified by geographical region. Results: Seventy-three cases from nine distinct geographical regions were included in the primary analyses. In comparison to White children, the relative risk for developing MIS-C after SARS-CoV-2 infection was 15 [95% confidence interval (CI): 7.1 to 32] for Black children, 11 (CI: 2.2 to 57) for Asian, and 1.6 (CI: 0.58 to 4.2) for other ethnic background. Conclusion: Pediatricians should be aware of the fact that the risk of COVID-19-related MIS-C is severely increased in Black children.

2.
iScience ; 24(11): 103215, 2021 Nov 19.
Article in English | MEDLINE | ID: covidwho-1446746

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease.

3.
Archives of Disease in Childhood ; 106(Suppl 1):A431, 2021.
Article in English | ProQuest Central | ID: covidwho-1443543

ABSTRACT

BackgroundCoronavirus disease (COVID-19) pandemic has seen the emergence of a novel paediatric condition Paediatric Inflammatory Multisystem Syndrome Temporally associated with Severe acute respiratory syndrome coronavirus 2 (PIMS-TS). Royal College of Paediatric and Child Health guidance for the management of PIMS-TS recommends early discussion with relevant specialists in a multi-disciplinary team (MDT) setting.A regional MDT panel including representatives from cardiology, general paediatrics, infectious diseases, intensive care, rheumatology, research and pharmacy was established in May 2020 at pace with the evolution of PIMS -TS. Daily clinical decision support was provided using a video conference platform for all regional paediatric units.ObjectivesWe describe the evaluation of the newly configured PIMS-TS MDT, using a mixed-methods survey to capture user experience and feedback.MethodsEvaluation was conducted in July 2020. All users of the MDT service including chairpersons, panel members and referring clinicians were invited to complete the online survey. A 28-point questionnaire based on validated MDT evaluation methodology was developed and included 5 domains relevant to the PIMS-TS MDT: 1. Meeting organisation and process 2. Meeting infrastructure and logistics 3. Clinical decisions 4. Working and culture 5. Meeting feedback.ResultsSurvey response rate was 75%. Results from each domain is as below:Meeting organisation and process: – Users (90%) were aware of referral criteria, referral processes (86%) and MDT configuration including chairperson (90%) and panel members (75%). Majority were not aware (27%) or uncertain (25%) of specific meeting structure and protocols.Infrastructure & logistics: Majority (63%) found accessing videoconference platform straightforward (90%), with only (18%) reporting quality issues. Notably, nearly half the MDT users (49%) reported capacity and time restraints affecting their ability to attend the MDT.Clinical decisions: Clarity of clinical recommendations was acknowledged by majority (90%). Two thirds (65%) were aware of case referral proforma, nonetheless, majority were unsure or not aware of processes around post-MDT documentation in patient records.Working and culture: There was 98% agreement that MDT facilitated constructive discussion, supported learning and research and had positively impacted patient care.Meeting feedback: Rapid access to specialist expertise and complex decision-making support was universally acknowledged. Areas highlighted for improvement pertained to time and capacity constraints limiting participation, and to embed an MDT culture which encouraged inclusive, supportive behaviours and a collaborative team ethos.ConclusionsOur evaluation of the new PIMS-MDT demonstrates the process of agile adaptation to change followed by continuous learning and improvement, required to create efficient healthcare systems. User survey feedback identified excellent practice of achieving region-wide standardised care but also highlighted time and capacity constraints and the importance of fostering a supportive culture, which were subsequently incorporated in developing the MDT processes. Rapid implementation of system-wide changes at unprecedented scale and pace has been the norm during the COVID-19 pandemic, but this must be coupled with iterative cycles of learning and improvement to ensure optimal care.

5.
Br J Nutr ; : 1-26, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1225469

ABSTRACT

Coronavirus disease 2019 (COVID-19), has caused mild illness in children, until the emergence of the novel hyperinflammatory condition PIMS-TS: Paediatric Inflammatory Multisystem Syndrome Temporally associated with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PIMS-TS is thought to be a post- SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the United Kingdom (U.K), due to its postulated role in cytokine regulation and immune response. Eighteen children [median (range) age 8.9 (0.3 to 14.6) years, male=10] met the case definition. Majority were of Black, Asian and Minority Ethnic (BAME) origin [89%, 16/18]. Positive SARS-CoV-2 IgG antibodies were present in 94% (17/18) and RNA by PCR in 6% (1/18). 72% of the cohort were vitamin D deficient (<30nmol/L). The mean 25OHD concentration was significantly lower when compared to the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4-10 years) [24 vs 54nmol/L (95% CI: -38.6, -19.7); p<0.001]. The PICU group had lower mean 25OHD concentrations compared to the non-PICU group, but this was not statistically significant [19.5 vs 31.9 nmol/L; p=0.11]. The higher susceptibility of BAME children to PIMS-TS and also vitamin D deficiency merits contemplation. Whilst any link between vitamin D deficiency and the severity of COVID-19 and related conditions including PIMS-TS requires further evidence, public health measures to improve vitamin D status of the U.K BAME population has been long overdue.

6.
Circulation ; 143(1): 21-32, 2021 01 05.
Article in English | MEDLINE | ID: covidwho-1004233

ABSTRACT

BACKGROUND: The aim of the study was to document cardiovascular clinical findings, cardiac imaging, and laboratory markers in children presenting with the novel multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) infection. METHODS: This real-time internet-based survey has been endorsed by the Association for European Paediatric and Congenital Cardiologists Working Groups for Cardiac Imaging and Cardiovascular Intensive Care. Children 0 to 18 years of age admitted to a hospital between February 1 and June 6, 2020, with a diagnosis of an inflammatory syndrome and acute cardiovascular complications were included. RESULTS: A total of 286 children from 55 centers in 17 European countries were included. The median age was 8.4 years (interquartile range, 3.8-12.4 years) and 67% were boys. The most common cardiovascular complications were shock, cardiac arrhythmias, pericardial effusion, and coronary artery dilatation. Reduced left ventricular ejection fraction was present in over half of the patients, and a vast majority of children had raised cardiac troponin when checked. The biochemical markers of inflammation were raised in most patients on admission: elevated C-reactive protein, serum ferritin, procalcitonin, N-terminal pro B-type natriuretic peptide, interleukin-6 level, and D-dimers. There was a statistically significant correlation between degree of elevation in cardiac and biochemical parameters and the need for intensive care support (P<0.05). Polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was positive in 33.6%, whereas immunoglobulin M and immunoglobulin G antibodies were positive in 15.7% cases and immunoglobulin G in 43.6% cases, respectively, when checked. One child in the study cohort died. CONCLUSIONS: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with the Covid-19 pandemic. The majority of children have significantly raised levels of N-terminal pro B-type natriuretic peptide, ferritin, D-dimers, and cardiac troponin in addition to high C-reactive protein and procalcitonin levels. In comparison with adults with COVID-19, mortality in children with multisystem inflammatory syndrome associated with COVID-19 is uncommon despite multisystem involvement, very elevated inflammatory markers, and the need for intensive care support.


Subject(s)
Arrhythmias, Cardiac , COVID-19 , Pericardial Effusion , SARS-CoV-2 , Shock , Systemic Inflammatory Response Syndrome , Adolescent , Antibodies, Viral/blood , Arrhythmias, Cardiac/blood , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/therapy , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Child , Child, Preschool , Europe/epidemiology , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Interleukin-6/blood , Male , Natriuretic Peptide, Brain/blood , Pandemics , Peptide Fragments/blood , Pericardial Effusion/blood , Pericardial Effusion/epidemiology , Pericardial Effusion/etiology , Pericardial Effusion/therapy , Shock/blood , Shock/epidemiology , Shock/etiology , Shock/therapy , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/therapy
7.
Pediatr Cardiol ; 41(7): 1391-1401, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-593665

ABSTRACT

Children were relatively spared during COVID-19 pandemic. However, the recently reported hyperinflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome-"Paediatric Inflammatory Multisystem Syndrome-temporally associated with SARS-CoV-2" (PIMS-TS) has caused concern. We describe cardiac findings and short-term outcomes in children with PIMS-TS at a tertiary children's hospital. Single-center observational study of children with PIMS-TS from 10th April to 9th May 2020. Data on ECG and echocardiogram were retrospectively analyzed along with demographics, clinical features and blood parameters. Fifteen children with median age of 8.8 (IQR 6.4-11.2) years were included, all were from African/Afro-Caribbean, South Asian, Mixed or other minority ethnic groups. All showed raised inflammatory/cardiac markers (CRP, ferritin, Troponin I, CK and pro-BNP). Transient valve regurgitation was present in 10 patients (67%). Left Ventricular ejection fraction was reduced in 12 (80%), fractional shortening in 8 (53%) with resolution in all but 2. Fourteen (93%) had coronary artery abnormalities, with normalization in 6. ECG abnormalities were present in 9 (60%) which normalized in 6 by discharge. Ten (67%) needed inotropes and/or vasopressors. None needed extracorporeal life support. Improvement in cardiac biochemical markers was closely followed by improvement in ECG/echocardiogram. All patients were discharged alive and twelve (80%) have been reviewed since. Our entire cohort with PIMS-TS had cardiac involvement and this degree of involvement is significantly more than other published series and emphasizes the need for specialist cardiac review. We believe that our multi-disciplinary team approach was crucial for the good short-term outcomes.


Subject(s)
Coronavirus Infections/therapy , Heart Diseases/complications , Hospitals, Pediatric , Pneumonia, Viral/therapy , Systemic Inflammatory Response Syndrome/therapy , Betacoronavirus , COVID-19 , Child , Coronavirus Infections/complications , Echocardiography , Female , Heart Diseases/diagnostic imaging , Heart Diseases/therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Mucocutaneous Lymph Node Syndrome/complications , Pandemics , Patient Discharge , Pneumonia, Viral/complications , Retrospective Studies , SARS-CoV-2 , Stroke Volume , Systemic Inflammatory Response Syndrome/complications , Treatment Outcome , United Kingdom , Vasoconstrictor Agents/therapeutic use , Ventricular Function, Left
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