Presentation, Treatment Response and Short-Term Outcomes in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS).

Susanna Felsenstein,Phuoc Duong,Mary Boullier,Fiona Ryan,Giulia Varnier,Alice Chieng,Stephen Hughes,Jessica Jones,Olumoyin Awogbemi,Liza Mccann,Kamran Mahmood,Phil Riley,Christian M Hedrich,Emily Willis,Giridhar Soda,Hanna Lythgoe ,A G Cleary ,Claire Pain ,Janet E Mcdonagh ,David A Porter

doi:10.3390/jcm9103293

Abstract

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen responsible for Coronavirus Disease 2019 (COVID-19). Whilst most children and young people develop mild symptoms, recent reports suggest a novel paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Case definition and classification are preliminary, treatment is empiric and disease-associated outcomes are unclear. Here, we report 29 patients with PIMS-TS who were diagnosed, admitted and treated in the English North West between March and June 2020. Consistent with patterns observed internationally, cases peaked approximately 4 weeks after the initial surge of COVID-19-like symptoms in the UK population. Clinical symptoms included fever (100%), skin rashes (72%), cardiovascular involvement (86%), conjunctivitis (62%) and respiratory involvement (21%). Some patients had clinical features partially resembling Kawasaki disease (KD), toxic shock syndrome and cytokine storm syndrome. Male gender (69%), black, Asian and other minority ethnicities (BAME, 59%) were over-represented. Immune modulating treatment was used in all, including intravenous immunoglobulin (IVIG), corticosteroids and cytokine blockers. Notably, 32% of patients treated with IVIG alone went into remission. The rest required additional treatment, usually corticosteroids, with the exception of two patients who were treated with TNF inhibition and IL-1 blockade, respectively. Another patient received IL-1 inhibition as primary therapy, with associated rapid and sustained remission. Randomized and prospective studies are needed to investigate efficacy and safety of treatment, especially as resources of IVIG may be depleted secondary to high demand during future waves of COVID-19.

Highlights

Between March and June 2020, 29 children were admitted to tertiary paediatric centres in the English North West with a diagnosis of PIMS-TS (Alder Hey Children’s NHS Foundation Trust Hospital, Liverpool, n = 10; and Royal Manchester Children’s Hospital, n = 19)
This lagged behind the peak of adult admissions for COVID-19 to hospitals in the region by approximately 4 weeks and occurred well into the decline of COVID-19 in England (Figure 1) [57]; in keeping with PIMS-TS/multisystem inflammatory syndrome in children (MIS-C) cohorts described elsewhere [9]
Two-thirds of paediatric patients admitted with PIMS-TS (20/29; 69%) were male

Summary

Introduction

Since the advent of the Coronavirus Disease 2019 (COVID-19) pandemic, dominated by respiratory disease and evolution of acute respiratory distress syndrome (ARDS), cardiovascular compromise, excessive systemic inflammation and coagulopathy in adults [1,2,3], several countries affected by the coronavirus disease [4] pandemic have reported an unusually high number of cases of children hospitalized due to a multisystem inflammatory condition, at times requiring intensive care (Table S1) [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33]. With signs and symptoms reminiscent of systemic inflammatory responses partially resembling Kawasaki disease (KD), cytokine storm (CS) or toxic shock syndrome [36], commonly including a rash, conjunctivitis, abdominal pain and evidence of cardiac inflammation and/or injury [37]. To reach a consensus for evidence-based management guidance, diagnostic criteria have been defined (Table S2)

Methods

Results

Conclusion