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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308406

ABSTRACT

Paediatric multisystem inflammatory syndrome: temporally associated with SARS-COV-2 (PIMS-TS) is a well described rare but severe COVID-19 related syndrome. PIMS-TS have been reported in children from geographical areas of high COVID-19 infection. Most children with PIMS-TS require management in an intensive care unit with variable respiratory involvement. Adults recovering from COVID-19 infection have been reported to suffer from respiratory morbidity but such outcomes are unknown in children. We present the first report of normal short term respiratory outcomes as measured by spirometry in children with SARS-COV-2 antibody positive, PIMS-TS syndrome managed at a specialist children’s hospital in the UK.

2.
Br J Nutr ; 127(6): 896-903, 2022 03 28.
Article in English | MEDLINE | ID: covidwho-1651089

ABSTRACT

Coronavirus disease 2019 (COVID-19) has caused mild illness in children, until the emergence of the novel hyperinflammatory condition paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS). 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 UK, due to its postulated role in cytokine regulation and immune response. Eighteen children (median (range) age 8·9 (0·3-14·6) years, male = 10) met the case definition. The 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). Seventy-eight percentage of the cohort were vitamin D deficient (< 30 nmol/l). The mean 25OHD concentration was significantly lower when compared with the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4-10 years) (24 v. 54 nmol/l (95 % CI -38·6, -19·7); P < 0·001). The paediatric intensive care unit (PICU) group had lower mean 25OHD concentrations compared with the non-PICU group, but this was not statistically significant (19·5 v. 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 UK BAME population have been long overdue.


Subject(s)
COVID-19 , COVID-19/complications , Child , Child, Preschool , Humans , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Vitamin D
3.
Curr Opin Pediatr ; 33(6): 580-590, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1546081

ABSTRACT

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions. RECENT FINDINGS: Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources. SUMMARY: Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.


Subject(s)
COVID-19 , Nervous System Diseases/virology , Systemic Inflammatory Response Syndrome , COVID-19/complications , Child , Humans , Multicenter Studies as Topic , Pandemics
4.
Crit Care ; 25(1): 399, 2021 11 17.
Article in English | MEDLINE | ID: covidwho-1523316

ABSTRACT

BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic had a relatively minimal direct impact on critical illness in children compared to adults. However, children and paediatric intensive care units (PICUs) were affected indirectly. We analysed the impact of the pandemic on PICU admission patterns and patient characteristics in the UK and Ireland. METHODS: We performed a retrospective cohort study of all admissions to PICUs in children < 18 years during Jan-Dec 2020, using data collected from 32 PICUs via a central database (PICANet). Admission patterns, case-mix, resource use, and outcomes were compared with the four preceding years (2016-2019) based on the date of admission. RESULTS: There were 16,941 admissions in 2020 compared to an annual average of 20,643 (range 20,340-20,868) from 2016 to 2019. During 2020, there was a reduction in all PICU admissions (18%), unplanned admissions (20%), planned admissions (15%), and bed days (25%). There was a 41% reduction in respiratory admissions, and a 60% reduction in children admitted with bronchiolitis but an 84% increase in admissions for diabetic ketoacidosis during 2020 compared to the previous years. There were 420 admissions (2.4%) with either PIMS-TS or COVID-19 during 2020. Age and sex adjusted prevalence of unplanned PICU admission reduced from 79.7 (2016-2019) to 63.1 per 100,000 in 2020. Median probability of death [1.2 (0.5-3.4) vs. 1.2 (0.5-3.4) %], length of stay [2.3 (1.0-5.5) vs. 2.4 (1.0-5.7) days] and mortality rates [3.4 vs. 3.6%, (risk-adjusted OR 1.00 [0.91-1.11, p = 0.93])] were similar between 2016-2019 and 2020. There were 106 fewer in-PICU deaths in 2020 (n = 605) compared with 2016-2019 (n = 711). CONCLUSIONS: The use of a high-quality international database allowed robust comparisons between admission data prior to and during the COVID-19 pandemic. A significant reduction in prevalence of unplanned admissions, respiratory diseases, and fewer child deaths in PICU observed may be related to the targeted COVID-19 public health interventions during the pandemic. However, analysis of wider and longer-term societal impact of the pandemic and public health interventions on physical and mental health of children is required.


Subject(s)
COVID-19/epidemiology , Intensive Care Units, Pediatric/statistics & numerical data , Pandemics , Patient Admission/statistics & numerical data , Child , Humans , Ireland/epidemiology , Retrospective Studies , United Kingdom/epidemiology
5.
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.

6.
Lancet Child Adolesc Health ; 4(9): 669-677, 2020 09.
Article in English | MEDLINE | ID: covidwho-1386995

ABSTRACT

BACKGROUND: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). FINDINGS: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85-1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 µg/L to 1659 µg/L), and ferritin (1042 µg/L to 757 µg/L), whereas the lymphocyte count increased to more than 1·0 × 109 cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died. INTERPRETATION: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown. FUNDING: None.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Intensive Care Units, Pediatric/statistics & numerical data , Patient Admission/trends , Pneumonia, Viral/complications , Systemic Inflammatory Response Syndrome/therapy , Adolescent , COVID-19 , Child , Coronavirus Infections/epidemiology , Female , Humans , Incidence , Male , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/etiology , United Kingdom/epidemiology
10.
Crit Care Explor ; 3(3): e0362, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1156824

ABSTRACT

OBJECTIVES: Severe acute respiratory syndrome coronavirus-2 affects adults disproportionately more than children. A small proportion of children with severe acute respiratory syndrome coronavirus-2 required admission to a PICU. We describe the nationwide U.K. PICU experience of severe acute respiratory syndrome coronavirus-2 infection during the first wave of the pandemic and compare this with the critical care course of the 2019 influenza cohort. DESIGN: Prospective nationwide cohort study of characteristics of severe acute respiratory syndrome coronavirus-2-positive children. Data collection utilized routine Pediatric Intensive Care Audit Network and severe acute respiratory syndrome coronavirus-2-specific data. SETTING: All U.K. PICUs. PATIENTS: Children less than 18 years old, admitted to U.K. PICUs between March 14, 2020, and June 13, 2020, and a positive severe acute respiratory syndrome coronavirus-2 polymerase chain reaction. Children admitted to U.K. PICUs in 2019 with influenza provided comparison. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 76 PICU admissions among 73 children with a positive severe acute respiratory syndrome coronavirus-2 polymerase chain reaction test. Prevalence of PICU admissions per million was 5.2 for children versus 260 for adults. Ten children (14%) were identified on routine screening. Seventeen children (23%) had pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Seventeen (23%) had coinfections. Invasive ventilation was required in seven of 17 children (41%) with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 versus 38 of 56 other severe acute respiratory syndrome coronavirus-2 positive children (68%), with 77% requiring vasoactive support versus 43%, respectively. Seven children (10%) died. In comparison with influenza children, severe acute respiratory syndrome coronavirus-2 children were older (median [interquartile range]: 10 [1-13] vs 3 yr [1-8 yr]), more often Black or Asian (52% v 18%), higher weight z score (0.29 [-0.80 to 1.62] vs -0.41 [-1.37 to 0.63]), and higher deprivation index (3.3 [-1 to 6.3] vs 1.2 [-1.8 to 4.4]). Comorbidities, frequency of organ supports, and length of stay were similar. CONCLUSIONS: This nationwide study confirms that PICU admissions with severe acute respiratory syndrome coronavirus-2 infections were infrequent. We have reported similarities and differences in sociodemographic characteristics, organ support interventions, and outcomes of children affected by severe acute respiratory syndrome coronavirus-2 compared with influenza.

11.
Crit Care Med ; 48(12): 1809-1818, 2020 12.
Article in English | MEDLINE | ID: covidwho-970603

ABSTRACT

OBJECTIVES: To study the prevalence, evolution, and clinical factors associated with acute kidney injury in children admitted to PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. DESIGN: Multicenter observational study. SETTING: Fifteen PICUs across the United Kingdom. PATIENTS: Patients admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 between March 14, 2020, and May 20, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deidentified data collected as part of routine clinical care were analyzed. All children were diagnosed and staged for acute kidney injury based on the level of serum creatinine above the upper limit of reference interval values according to published guidance. Severe acute kidney injury was defined as stage 2/3 acute kidney injury. Uni- and multivariable analyses were performed to study the association between demographic data, clinical features, markers of inflammation and cardiac injury, and severe acute kidney injury. Over the study period, 116 patients with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 were admitted to 15 United Kingdom PICUs. Any-stage acute kidney injury occurred in 48 of 116 patients (41.4%) and severe acute kidney injury in 32 of 116 (27.6%) patients, which was mostly evident at admission (24/32, 75%). In univariable analysis, body mass index, hyperferritinemia, high C-reactive protein, Pediatric Index of Mortality 3 score, vasoactive medication, and invasive mechanical ventilation were associated with severe acute kidney injury. In multivariable logistic regression, hyperferritinemia was associated with severe acute kidney injury (compared with nonsevere acute kidney injury; adjusted odds ratio 1.04; 95% CI, 1.01-1.08; p = 0.04). Severe acute kidney injury was associated with longer PICU stay (median 5 days [interquartile range, 4-7 d] vs 3 days [interquartile range, 1.5-5 d]; p < 0.001) and increased duration of invasive mechanical ventilation (median 4 days [interquartile range, 2-6 d] vs 2 days [interquartile range, 1-3 d]; p = 0.04). CONCLUSIONS: Severe acute kidney injury occurred in just over a quarter of children admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Hyperferritinemia was significantly associated with severe acute kidney injury. Severe acute kidney injury was associated with increased duration of stay and ventilation. Although short-term outcomes for acute kidney injury in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 appear good, long-term outcomes are unknown.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , Intensive Care Units, Pediatric/statistics & numerical data , Systemic Inflammatory Response Syndrome/complications , Adolescent , Body Mass Index , COVID-19/epidemiology , Child , Humans , Hyperferritinemia/epidemiology , Logistic Models , Prevalence , Respiration, Artificial/statistics & numerical data , SARS-CoV-2 , Severity of Illness Index , Systemic Inflammatory Response Syndrome/epidemiology , United Kingdom/epidemiology
12.
J Pediatric Infect Dis Soc ; 10(3): 227-229, 2021 Apr 03.
Article in English | MEDLINE | ID: covidwho-780414

ABSTRACT

There is significant variability in the names and case definition of pediatric inflammatory multisystem syndrome associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Such variability leads to adverse consequences in the quest for further knowledge and management strategies. It is time to collaborate to gain consensus.


Subject(s)
COVID-19/pathology , Systemic Inflammatory Response Syndrome/virology , Adolescent , COVID-19/virology , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Mucocutaneous Lymph Node Syndrome/pathology , Mucocutaneous Lymph Node Syndrome/virology , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome/pathology
14.
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
15.
Hosp Pediatr ; 10(9): 802-805, 2020 09.
Article in English | MEDLINE | ID: covidwho-592333

ABSTRACT

OBJECTIVES: Reports from China relating to coronavirus disease (COVID-19) in children indicate a milder disease course compared with adults. Although a few pediatric COVID-19 reports from other parts of the world exist, there are none from the United Kingdom. We describe the clinical characteristics of children with COVID-19 admitted to a specialist children's hospital in United Kingdom. METHODS: Retrospective case-series of inpatients with a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2, during a 6-week period from March 14 to April 24, 2020. RESULTS: Forty-five children tested positive for severe acute respiratory syndrome coronavirus 2 during the study period. Median (interquartile range) age was 3.5 (0.7-12) years, and 31 (69%) were male. Children with comorbidities constituted 64% (29 of 45) of the study population, including 44% (20 of 45) who were considered "extremely vulnerable." Fever (67%) and cough (55%) were the most common symptoms. High C-reactive protein (>10 mg/L) was observed in 68% (19 of 28). Lymphopenia (<1.2 × 109/L) was observed in 23% (9 of 40) of children, but it was related to coexisting medical conditions in 6 children. Nine children required supplemental oxygen, two of whom received high-flow nasal cannula oxygen; one needed noninvasive ventilation and one child required invasive mechanical ventilation. Median length of stay of children with an admission outcome (n = 42, 93%) was 3 (2-7) days. There were no COVID-19-related deaths. CONCLUSIONS: COVID-19 had a relatively mild course of illness in majority of the hospitalized children that included a subgroup of vulnerable children with significant comorbidities. Confirmation of this in larger nationwide studies of children is required.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Health Status , Pneumonia, Viral/therapy , Severity of Illness Index , Adult , COVID-19 , Child , Child, Preschool , Female , Hospitals, Pediatric , Humans , Male , Pandemics , Retrospective Studies , SARS-CoV-2 , United Kingdom
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