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ssrn; 2020.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.3692427


Background: Clinicians observed a cluster of children with unexplained inflammation requiring admission to United Kingdom (UK) paediatric intensive care units (PICUs) in April 2020. Despite multiple guidelines, which treatments are effective in Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) is unknown.Methods: Multicentre observational study of children (<18 years) admitted to UK PICUs between 1 April and 10 May 2020, fulfilling the case definition of PIMS-TS. Routinely collected, de-identified data was analysed. Linear mixed effects models were used to analyse the effect of steroids, intravenous immunoglobulin (IVIG), and biologic agents on C-reactive protein (CRP), platelet counts,and lymphocyte counts. The content of UK clinical guidelines was collated. Findings: Over the six week study period: 59/78 (76%) children received IVIG, 57/78 (73%) steroids, and 17/78 (22%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with PIMS-TS who were treated with IVIG, steroids or biologics, compared to those who were not. Despite a progression to near universal treatment with immunomodulators, the proportion of patients with coronary artery abnormalities increased. Guidelines universally advised or considered the use of IVIG, steroids, and biologics. Interpretation: We were unable to identify any short term benefit from any of the treatments, or treatment combinations administered. Despite a lack of evidence, worldwide treatment guidelines for PIMS-TS have become very similar. Clinicians treating PIMS-TS should continue to have equipoise and participate in robust clinical trials of all treatments currently being utilised for this important condition. Funding: NoneDeclaration of Interests: All authors have completed the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest, and have no conflicts of interest to disclose.Ethics Approval Statement: The project was classified as a service evaluation by the Nottingham Research and Innovation team (Nottingham Clinical Effectiveness Team ref: 20- 235C), and ethics approval was not required. The study team analysed routinely collected de-identified data submitted by clinicians from the individual PICUs as a local service evaluation. Clinicians obtained informed parental consent if required locally.

Coronary Artery Disease , Cryopyrin-Associated Periodic Syndromes
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.08.20.20178541


BackgroundThe paucity of data describing SARS-CoV-2 in the paediatric population necessitated a broad-arching approach to pandemic planning, with preparations put in place to manage a heterogeneous cohort. We describe a diverse group of SARS-CoV-2 positive paediatric patients treated at a large tertiary/quaternary childrens hospital in the United Kingdom and the adaptive coping strategies required. MethodsAll paediatric patients with positive RT-PCR on a respiratory sample and/or serology for SARS-CoV-2 up to 19th May 2020 were included. Results57 children met the inclusion criteria. 70% were of non-Caucasian ethnicity with a median age of 9.3 years (IQR 5.16-13.48). Four distinct groups were identified: paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) (54%), primary respiratory (18%), incidental (7%), and non-specific febrile illnesses with or without extra-pulmonary organ dysfunction (21%). These groups presented in distinct chronological blocks as the pandemic unfolded. DiscussionThe diverse range of presentations of SARS-CoV-2 infection in this population exemplified the importance of preparedness for the unknown in the midst of a novel infectious pandemic. Descriptions of paediatric patients during the initial phase of the pandemic from other parts of the globe and extrapolation from adult data did not serve as an accurate representation of paediatric COVID-19 in our centre. An adaptive, multidisciplinary approach was paramount. Expanded laboratory testing and incorporation of technology platforms to facilitate remote collaboration in response to strict infection control precautions were both indispensable. Lessons learned during the preparation process will be essential in planning for a potential second wave of SARS-CoV-2.