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Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2

Educational Objective
To understand the clinical and laboratory characteristics of critically ill children with inflammatory multisystem syndrome during COVID-19
1 Credit CME
Key Points

Question  What are the clinical and laboratory characteristics of critically ill children who developed an inflammatory multisystem syndrome during the coronavirus disease 2019 pandemic?

Findings  This case series included 58 hospitalized children, a subset of whom required intensive care, and met definitional criteria for pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS), including fever, inflammation, and organ dysfunction. Of these children, all had fever and nonspecific symptoms, such as abdominal pain (31 [53%]), rash (30 [52%]), and conjunctival injection (26 [45%]); 29 (50%) developed shock and required inotropic support or fluid resuscitation; 13 (22%) met diagnostic criteria for Kawasaki disease; and 8 (14%) had coronary artery dilatation or aneurysms. Some clinical and laboratory characteristics had important differences compared with Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome.

Meaning  These findings help characterize the clinical features of hospitalized, seriously ill children with PIMS-TS and provide insights into this apparently novel syndrome.

Abstract

Importance  In communities with high rates of coronavirus disease 2019, reports have emerged of children with an unusual syndrome of fever and inflammation.

Objectives  To describe the clinical and laboratory characteristics of hospitalized children who met criteria for the pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) and compare these characteristics with other pediatric inflammatory disorders.

Design, Setting, and Participants  Case series of 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020, with persistent fever and laboratory evidence of inflammation meeting published definitions for PIMS-TS. The final date of follow-up was May 22, 2020. Clinical and laboratory characteristics were abstracted by medical record review, and were compared with clinical characteristics of patients with Kawasaki disease (KD) (n = 1132), KD shock syndrome (n = 45), and toxic shock syndrome (n = 37) who had been admitted to hospitals in Europe and the US from 2002 to 2019.

Exposures  Signs and symptoms and laboratory and imaging findings of children who met definitional criteria for PIMS-TS from the UK, the US, and World Health Organization.

Main Outcomes and Measures  Clinical, laboratory, and imaging characteristics of children meeting definitional criteria for PIMS-TS, and comparison with the characteristics of other pediatric inflammatory disorders.

Results  Fifty-eight children (median age, 9 years [interquartile range {IQR}, 5.7-14]; 20 girls [34%]) were identified who met the criteria for PIMS-TS. Results from SARS-CoV-2 polymerase chain reaction tests were positive in 15 of 58 patients (26%) and SARS-CoV-2 IgG test results were positive in 40 of 46 (87%). In total, 45 of 58 patients (78%) had evidence of current or prior SARS-CoV-2 infection. All children presented with fever and nonspecific symptoms, including vomiting (26/58 [45%]), abdominal pain (31/58 [53%]), and diarrhea (30/58 [52%]). Rash was present in 30 of 58 (52%), and conjunctival injection in 26 of 58 (45%) cases. Laboratory evaluation was consistent with marked inflammation, for example, C-reactive protein (229 mg/L [IQR, 156-338], assessed in 58 of 58) and ferritin (610 μg/L [IQR, 359-1280], assessed in 53 of 58). Of the 58 children, 29 developed shock (with biochemical evidence of myocardial dysfunction) and required inotropic support and fluid resuscitation (including 23/29 [79%] who received mechanical ventilation); 13 met the American Heart Association definition of KD, and 23 had fever and inflammation without features of shock or KD. Eight patients (14%) developed coronary artery dilatation or aneurysm. Comparison of PIMS-TS with KD and with KD shock syndrome showed differences in clinical and laboratory features, including older age (median age, 9 years [IQR, 5.7-14] vs 2.7 years [IQR, 1.4-4.7] and 3.8 years [IQR, 0.2-18], respectively), and greater elevation of inflammatory markers such as C-reactive protein (median, 229 mg/L [IQR 156-338] vs 67 mg/L [IQR, 40-150 mg/L] and 193 mg/L [IQR, 83-237], respectively).

Conclusions and Relevance  In this case series of hospitalized children who met criteria for PIMS-TS, there was a wide spectrum of presenting signs and symptoms and disease severity, ranging from fever and inflammation to myocardial injury, shock, and development of coronary artery aneurysms. The comparison with patients with KD and KD shock syndrome provides insights into this syndrome, and suggests this disorder differs from other pediatric inflammatory entities.

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Article Information

Corresponding Author: Michael Levin, MD, Department of Infectious Diseases, Imperial College London, Norfolk Place, London, Greater London W21NY, United Kingdom (m.levin@imperial.ac.uk).

Accepted for Publication: May 29, 2020.

Published Online: June 8, 2020. doi:10.1001/jama.2020.10369

Correction: This article was corrected online June 30, 2020, to fix the numbers and percentages of patients in certain groups reported in the Results section of the Abstract and text and Table 2, as well as add names to the list of group investigators in Supplement 2.

Author Contributions: Drs Whittaker and Kaforou had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Whittaker, Bamford, Kenny, and Kaforou contributed equally. Drs Lyall and Levin contributed equally.

Concept and design: Whittaker, Bamford, Jones, Kucera, McDougall, Carter, Lyall, Levin.

Acquisition, analysis, or interpretation of data: Whittaker, Bamford, Kenny, Kaforou, Jones, Shah, Ramnarayan, Fraisse, Miller, Davies, Brierley, McDougall, Carter, Tremoulet, Shimizu, Herberg, Burns.

Drafting of the manuscript: Whittaker, Bamford, Kenny, Kaforou, Jones, Miller, Davies, Kucera, Levin.

Critical revision of the manuscript for important intellectual content: Whittaker, Bamford, Kenny, Kaforou, Jones, Shah, Ramnarayan, Fraisse, Brierley, McDougall, Carter, Tremoulet, Shimizu, Herberg, Burns, Lyall, Levin.

Statistical analysis: Whittaker, Kaforou, Shah, Shimizu.

Obtained funding: Whittaker, Kaforou, Tremoulet, Shimizu, Herberg, Burns, Levin.

Administrative, technical, or material support: Kenny, Kaforou, Jones, McDougall, Carter, Levin.

Supervision: Kaforou, Fraisse, McDougall, Lyall, Levin.

Conflict of Interest Disclosures: Dr Fraisse reported consultantship and proctoring for transcatheter congenital interventions from Abbott, Occlutech, and Medtronic. Dr Shimizu reported receiving grants from the Gordon and Marilyn Macklin Foundation. No other disclosures were reported.

Funding/Support: Drs Kaforou, Whittaker, Shah, Herberg, and Levin receive support from the UK National Institute for Health Research (NIHR) Imperial Biomedical Research Centre. Dr Kaforou is funded by the Wellcome Trust (Sir Henry Wellcome Fellowship grant 206508/Z/17/Z). This project received funding from the European Union’s Seventh Framework programme under grant agreement 279185 (EUCLIDS) and the European Union’s Horizon 2020 research and innovation programme under grant agreement 668303 (PERFORM). Dr Burns, Tremoulet, and Shimizu were supported in part by grant R01HL140898 from the National Institutes of Health. This work is supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed are those of the author(s) and not necessarily those of the UK National Health Service, the NIHR, or the Department of Health.

Additional Contributions: This work would not have been possible without collaboration between 3 NIHR biomedical research center facilities: Great Ormond Street, Imperial College London, and Guy’s & St Thomas’.

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