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1.
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.

2.
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.

3.
Archives of Disease in Childhood ; 106(Suppl 1):A378, 2021.
Article in English | ProQuest Central | ID: covidwho-1443521

ABSTRACT

BackgroundCoronavirus 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.ObjectivesThere has been a long-standing interest in the role of 25 hydroxyvitamin D (25OHD) in cytokine-storm induced critical illnesses due to the premise of its anti-inflammatory actions including regulation of cytokine release. Vitamin D deficiency in critically ill individuals in intensive care has been linked to poor cardiovascular outcome and increased mortality.We report the vitamin D status of children with PIMS-TS admitted to a single tertiary paediatric hospital in the Midlands region of the United Kingdom (U.K).MethodsWe studied 25OHD levels in children admitted to a tertiary paediatric hospital in the U.K., fulfilling the case definition of PIMS-TS detailed by the Royal College of Paediatrics and Child Health. Children were managed either on paediatric intensive care unit (PICU group) or on the wards (non-PICU group). 25OHD concentrations were measured by quantitative liquid chromatography tandem mass spectrometry. Statistical analysis used a two-sample t-test, assuming unequal variances.ResultsFifty children [median (range) age 8.8 (0.99 to 14.6) years, male = 24] met the case definition. The majority were of Black, Asian and Minority Ethnic (BAME) origin [78%, 39/50]. SARS-CoV-2 IgG antibodies were confirmed in 64% (32/50) and SARS-CoV-2 RNA detected by PCR in 6% (3/50) of the study population. Of those patients without serology or PCR data available, the majority had a confirmed Covid 19 positive contact.Eighty-two percent 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, a cohort of healthy children with no medical conditions, aged 4–10 years [22 vs 54nmol/L (95% CI: 15.9, 24.1);p<0.001]. Children from BAME backgrounds had reduced vitamin D levels compared to children from a white background [mean 25OHD concentration 17.7 vs 28.2;p=0.12]. The PICU group had lower mean 25OHD concentrations compared to the non-PICU group, although this was not statistically significant [16.9 vs 28 nmol/L;p=0.071].ConclusionsPIMS-TS has seen an over-representation of children from BAME background, who are also at greatest risk of vitamin D deficiency. 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. Given the safety profile of vitamin D supplementation and the over-representation of BAME individuals with vitamin D deficiency and PIMS-TS, mandated year-round supplementation of all high-risk children should be the way forward.

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.
Lancet Child Adolesc Health ; 4(9): 653-661, 2020 09.
Article in English | MEDLINE | ID: covidwho-613887

ABSTRACT

BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Delivery of Health Care/organization & administration , Intensive Care Units/organization & administration , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , Child , Child, Preschool , Coronavirus Infections/therapy , Europe/epidemiology , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Patient Admission/trends , Pneumonia, Viral/therapy , Risk Factors , SARS-CoV-2
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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