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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.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-291469

ABSTRACT

Purpose: To define the burden of morbidity and mortality arising from COVID-19 in individuals with primary (PID) and secondary immunodeficiency (SID) in the United Kingdom. Methods In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. Anonymised demographic data, pre-SARS-CoV-2 infection lymphocyte counts, co-morbidities, targeted treatments and outcomes were collected. Three groups were analysed in further detail: individuals with common variable immunodeficiency (CVID), individuals with any PID, including CVID, receiving immunoglobulin replacement therapy (IgRT) and individuals with secondary immunodeficiency. Results A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID, had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Conclusion Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.

4.
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.

5.
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.

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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