COVID-19: A UK Children's Hospital Experience.

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.

Early assessment and treatment of children with paediatric inflammatory multisystem syndrome-temporally related to SARS-CoV-2 (PIMS-TS): a service evaluation

975 Figure 1 975 Figure 2Our results demonstrate that over the 9-month service evaluation period, there was an overall reduction in the time taken to diagnose PIMS-TS. Awareness of the disease and pattern recognition would have been key enablers for this improvement. At the start of our evaluation in May 2020, PIMS-TS was just starting to be recognised as a distinct disease whereas by February 2021 the disease is well recognised by general paediatricians.Our data showed a relatively consistent pattern in timing from diagnosis to commencement of all three specific modalities of treatment. Variation in timing of initiation of Aspirin is appropriately related to delay in recovery of platelet counts to above 150, as recommended in local treatment guidelines.As incidence of COVID-19 continued to rise and further waves of PIMS-TS cases were predicted, findings from the service evaluation were used to identify an action plan for general paediatrics service. This included raising awareness of PIMS-TS for frontline clinicians by dissemination of the service evaluation findings and holding PIMS-TS learning events. Early initiation of treatment was encouraged by providing PIMS-TS guidance on immunomodulatory and supportive therapies. Clear pharmacy guidelines were produced for ward-based administration of treatments.Early recognition and appropriate treatment of PIMS-TS is critical for ensuring good outcomes and the service evaluation has had a crucial role in generating information and actions to benefit patients by improving the existing care pathway.

Critical Care Course of Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 and Response to Immunomodulation

We describe the critical care course of children with a novel hyperinflammatory syndrome associated with coronavirus disease 2019 (COVID-19) pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with focus on trajectory before and after immunomodulation. Overall, 10 patients who met the U.K. Royal College of Pediatrics and Child Health case definition during a 2-month study period were analyzed. All tested positive for SARS-CoV-2 IgG antibody. Although only 20% were ventilated, 100% required inotropic or vasopressor support. All children had significantly raised inflammatory markers with a median C-reactive protein of 248 (175–263) mg/L, ferritin of 1,561 (726–2,255) µg/L, and troponin-I of 723 (351–2,235) ng/L. Six patients had moderately impaired myocardial function and two had severe impairment. None needed extracorporeal membrane oxygenation. Despite severe illness only a brief period of critical care support of 3 to 5 days was required. Eight received at least one dose of intravenous immunoglobulin. Six received high-dose steroids. Clinical improvement including cardiovascular stability and reduction in inflammatory markers may have occurred with and without immunomodulation.

Vitamin D status of children with paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS).

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.

The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery.

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.

Evaluation of a multidisciplinary team model of care in paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS)

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.

Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS) and Vitamin D deficiency

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.

Designing a global health partnership evaluation

BackgroundBirmingham Women’s and Children’s Hospital (BWC)- Malawi Partnership is a global health partnership (GHP) established in 2004 as an educational link between paediatric departments at BWC and Queen Elizabeth Central Hospital (QECH), Malawi. Regular monitoring and evaluation of GHPs is key for assessing relevance, effectiveness, efficiency, impact and sustainability.ObjectivesDesign a global health partnership evaluation in accordance with internationally accepted standards to accurately capture the impact of the BWC-Malawi Partnership.MethodsAn evaluation strategy was co-developed between BWC and QECH. The evaluation methodology was designed to assess contribution of the Partnership in accordance with its vision of improving child health sustainably through education and training. Domains for assessment were based on established determinants of effectiveness for GHPs1 2 and included shared vision and goals, commitment to joint learning, sustainable, accountable, respectful, reciprocal and responsible.A mixed-methods approach was adopted using quantitative questionnaires, semi-structured interviews and focus groups at both sites. Questions were written in consultation with the QECH team to ensure they were appropriate to the local context and to reduce communication barriers. Questions focused on specific Partnership education and training activities including bi-directional exchanges, specialty teaching visits and the Paediatric Assessment Skills (PAS) course.Operational planning involved input from both organisations, scheduling interviews to ensure representative numbers from all multi-professional staff groups, avoiding disruption to clinical care and ensuring interview techniques were empathetic and allowed equitable access to all voices. Practical measures included recruiting an evaluation team with previous knowledge of the artnership, timely advertising of the evaluation, organising rooms and timetabling staff for interviews, sourcing equipment, arranging travel itinerary and accommodation.ResultsA quantitative questionnaire consisting of nine closed-answer and Likert scale questions was devised, as well as thirteen questions for the semi-structured individual interviews, to complete in fifteen minutes. Mock interviews were conducted to test for understanding and time management.Due to the COVID-19 pandemic, a digital questionnaire method of evaluation was used for interviewing BWC.All aspects of the design and implementation was completed in time for the evaluation. Designing the evaluation and organising the strategic, operational and practical aspects of the evaluation took two months to complete.ConclusionsEvaluation is essential for effectiveness, credibility and accountability of GHP. Planning and perfecting the details of the evaluation to be context specific, capture key components of artnership interventions, address equity, collaboration and governance, requires considerable investment of time and manpower from both partners. Partnerships should take this into account while planning evaluations to ensure success of the process and sustainability of the artnership. Advance design of evaluation instruments and processes which are specific and relevant to the partnership circumstances is crucial for the collection of reliable information.ReferencesTHEThttps://www.oecd.org/dac/evaluation/49756382.pdf

Evaluation of a global health partnership

1349 Table 1Impact on practice at QECHChanges in the workplace Clinical Management Professional Practice Induction for new nursesTriageColour-coded syringes for oral and IVTelevision installed in ward(after seeing similar at BWC) Seizure, asthma managementFluid management in malnourished childChild protectionIncreased frequency of measuring vital signsInitiating resuscitationHand hygiene Intra- and inter-disciplinary team workTime keepingIncreased competence and confidenceAutonomy and decision makingMotivation Abstract 1349 Table 2Impact on practice at BWCChanges in the workplace Clinical management Professional practice More resourcefulEmpathy and cultural awarenessCreating a supportive environment Increased clinical knowledgeConfidence in managing sick patientsMore confidence, autonomy Better leaderInnovative and adaptive practiceCost-effective approachMentorshipExperience in teaching Evaluation also revealed areas of suboptimal engagement, such as a sense of inequity in the exchange placements which involves a 2-week observership in Birmingham for Malawi staff compared to a 6–12-month placement for BWC staff in Malawi. Lack of a nursing contact in Malawi to co-ordinate nurse placements was also highlighted.Recommendations included continuing educational courses and refreshers, increasing peer support and establishing a nurse link in Malawi. Future priorities were to establish services for common childhood conditions like asthma and epilepsy and improvements to exchange placements.The BWC evaluation, which had to be changed to virtual interviews due to COVID-19 pandemic restrictions, highlighted the need for urgent evaluation of post-pandemic modes of working.ConclusionsGHP evaluations form the cornerstone of effective partnerships by evidencing successes as well as determining areas for improvements and goal setting. Well-conducted evaluations enable identification of SMART objectives for future actions. While the COVID-19 pandemic has reiterated the concept of health interdependence, it has also shown that GHPs including BWC-Malawi partnership should be agile in tailoring their action plans to suit the post-pandemic world of limited international travel, with particular focus on digital health technologies.

Diagnostic accuracy of presenting symptoms in predicting SARS-CoV-2-positivity

BackgroundClinical characterisation studies of children with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have enabled better understanding of paediatric coronavirus disease 2019 (COVID-19). However, to our knowledge, there have been no studies evaluating the predictive value of clinical symptoms for paediatric COVID-19. This gap in evidence is significant as frontline healthcare settings use clinical symptoms to determine infection control policy and patient cohorting measures.Despite studies showing that children have a mild illness, the risk of children with comorbidities and other clinical vulnerabilities contracting COVID-19 remains poorly defined.Objectives• To determine the diagnostic accuracy of presenting clinical symptoms in predicting SARS-CoV-2 positivity.• To assess the co-relation of demographic characteristics, clinical co-morbidities and vulnerabilities with SARS-CoV-2 positivity.MethodsRetrospective single-centre observational study of children with suspected COVID-19 who underwent SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing on admission to a specialist children’s hospital in the United Kingdom. Data was collected from electronic patient records from 17/03/2020 to 14/04/2020.Results210 children, aged 0–16 years, median age of 2.5 years (Interquartile range 0.7–7.0) were included. 29 (14%) were SARS-CoV-2-positive. A higher proportion of SARS-CoV-2-positive children were male (62% vs 50%, p=0.24) and at the extremes of age (below 6 months and above 10 years).SARS-CoV-2 positive group had a higher incidence of diarrhoea, vomiting, abdominal pain and seizures whereas cough was seen more frequently in the SARS-CoV-2 negative group. Proportions of children presenting with any respiratory symptoms was similar in both SARS-CoV-2 positive and negative groups. Sensitivity of clinical symptoms individually or in combination in predicting SARS-CoV-2 positivity was 70% or lower. Specificity for predicting SARS-CoV-2 positivity was more than 80% for wheeze, abdominal pain, diarrhea and vomiting, reduced feeds, fever, lethargy, rash and headache.There were significantly more children of Black, Asian and Minority ethnic (BAME) groups in the SARS-CoV-2-positive group (72% [21/29] vs 46% [84/181], p=0.009).Proportions of children with comorbidities in both SARS-CoV-2-positive and negative groups were similar;48% (14/29) vs 54% (97/181) respectively (p=0.59). The commonest comorbidity in this study cohort were respiratory conditions, followed by neurological and oncological conditions.The proportion of children who tested SARS-CoV-2 positive was similar between the clinically vulnerable and non-vulnerable groups. (13.5% [7/52] vs 13.9% [22/158];p=0.85).ConclusionsIn our study cohort, there was no single symptom or cluster of symptoms predictive of a positive SARS-CoV-2 test. The only association that we found with SARS-CoV-2 positivity was belonging to a BAME group. Having comorbidities or being clinically vulnerable did not increase the likelihood of a children being SARS-CoV-2 positive.As presenting symptoms are not accurately predictive of SARS-CoV-2 detection, our study suggests that cohorting children based on clinical symptoms alone, could potentially increase the risk of transmission of infection within healthcare facilities. Until rapid and accurate point-of-care testing is widely available, a shift of emphasis from symptom-based cohorting towards measures such as physical distancing and use of face coverings, will enable better protection.

A research journey in the time of corona virus disease (COVID-19)

BackgroundCOVID-19 has seen a global research effort to address the pandemic and U.K has been at its forefront with flagship trials such as RECOVERY trial which have transformed COVID-19 management. RECOVERY trial involved hospitals and healthcare professionals in research in an unprecedented scale and provided opportunities for trainees to engage in research.While children have been relatively spared from acute COVID-19, emergence of the novel hyperinflammatory condition Paediatric Inflammatory Multisystem Syndrome Temporally associated with Severe Acute Respiratory Syndrome Coronavirus 2 (PIMS-TS) was a diagnostic and treatment dilemma. Commencement of treatment trials for PIMS-TS in the paediatric arm of RECOVERY trial coincided with the roll out of NIHR Associate PI scheme, which is an opportunity for trainees to gain experience in research.ObjectivesWe aim to describe the trainee experience of research during COVID-19, as part of the RECOVERY trial team at a specialist children’s hospital.MethodsInterviews were undertaken with non-consultant grade paediatricians involved with the RECOVERY trial as Associate PIs, regarding their research journey.ResultsUndertaking the Associate PI scheme was a structured introduction to research, requiring completion of the training and familiarity with trial protocol. As a specialist children’s hospital with a regional paediatric intensive care unit, the number of patients eligible to participate in the trial increased rapidly during the peaks of the pandemic. The increment in numbers meant that Associate PIs had to be skilled up quickly in all the aspects of this ‘platform trial’ which evaluates several drugs at the same time. However, the pragmatic trial methods which aim to ease research recruitment for the busy clinician with minimal burden to families and the excellent training resources instilled confidence in embarking on the research journey.Informed consent process was an iterative learning journey where the theoretical understanding of consent and assent in paediatric trials was followed by a very different learning curve of real-life consent process. Understanding consent as an information cycle rather than a single process and balancing the needs of the carers of a sick child empathetically was a skill developed by observing the consent process before independently recruiting. Valuable communication skills were gained as COVID-19 visiting restrictions meant discussions with non-visiting parents and occasionally obtaining remote consent. Team working in collaboration with research nurses and pharmacists was another benefit of the research journey. Attending the regional PIMS/COVID MDT discussions where standardised treatment and research decisions were undertaken, enhanced the knowledge and experience in clinical management of these patients.ConclusionsOverall it has been rewarding to have contributed to one of the largest recruiting COVID-19 research trials, thus making a difference to children’s outcomes. Furthermore, the RECOVERY trial and Associate PI scheme have provided unique research opportunities hitherto unavailable for trainees in general paediatrics and embarking on this journey has cemented our intention to continue research engagement as part of day-to-day clinical practice.

Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020.

BACKGROUND: Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland. METHODS: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included. FINDINGS: There were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14.8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63.6% (75/118) were positive for SARS-CoV-2 antibodies. In total 44·0% (118/268) required intensive care, which was more common in cases with a TSS phenotype. Three of five children with cardiac arrest had TSS phenotype. Three children (1·1%) died. INTERPRETATION: The strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS. FUNDING: PHE.

Critical Care Course of Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 and Response to Immunomodulation.

We describe the critical care course of children with a novel hyperinflammatory syndrome associated with coronavirus disease 2019 (COVID-19) pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with focus on trajectory before and after immunomodulation. Overall, 10 patients who met the U.K. Royal College of Pediatrics and Child Health case definition during a 2-month study period were analyzed. All tested positive for SARS-CoV-2 IgG antibody. Although only 20% were ventilated, 100% required inotropic or vasopressor support. All children had significantly raised inflammatory markers with a median C-reactive protein of 248 (175-263) mg/L, ferritin of 1,561 (726-2,255) µg/L, and troponin-I of 723 (351-2,235) ng/L. Six patients had moderately impaired myocardial function and two had severe impairment. None needed extracorporeal membrane oxygenation. Despite severe illness only a brief period of critical care support of 3 to 5 days was required. Eight received at least one dose of intravenous immunoglobulin. Six received high-dose steroids. Clinical improvement including cardiovascular stability and reduction in inflammatory markers may have occurred with and without immunomodulation.

Paediatric Inflammatory Multisystem Syndrome: Temporally Associated with SARS-CoV-2 (PIMS-TS): Cardiac Features, Management and Short-Term Outcomes at a UK Tertiary Paediatric Hospital.

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.