Paediatric Inflammatory Multisystem Syndrome During COVID-19 Pandemic

NCT ID: NCT04761913

Last Updated: 2022-02-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-06-22
• Study Completion Date: 2021-12-31

Brief Summary

During the COVID-19 pandemic, a small minority of children have been presenting to acute paediatric services with a new syndrome, Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-Cov-2 (PIMS-TS). Children with PIMS-TS present with symptoms of inflammation caused by the immune system going into overdrive - this is likely to be in response to the virus. More severe cases involve inflammation and damage to the heart.

The focus of this project is to identify children with milder forms of PIMS-TS who are at risk of progression to more severe disease. Being able to predict the disease course of PIMS-TS at an early stage is important as it will allow clinicians to decide which patients should be treated with immunosuppressants, which have been shown to reduce the severity of the illness but have side effects.

Early data suggests that children with PIMS-TS have elevated biomarkers associated with an over-reaction of the body's immune system (also known as a 'cytokine storm') reaction. This study will explore whether children presenting with milder PIMS-TS have elevated 'cytokine storm' blood profiles and whether these profiles differ between children who continue to have a mild disease course compared to those who develop severe disease.

Detailed Description

During the COVID-19 pandemic a minority of children have presented to acute services with clinical features of a new syndrome known as Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-Cov-2 (PIMS-TS). This high inflammatory state, likely triggered by the virus, has overlapping features of Kawasaki's and Toxic Shock Syndrome.

The focus of this study is to identify which children presenting with mild PIMS-TS symptoms will go on to develop severe disease requiring intensive care unit (ICU) admission. This is important as data suggests that early aggressive treatment with immunosuppression can lead to a relatively quick resolution in symptoms. The results of this study could allow clinicians to be selective in treating patients in whom the benefits of treatment outweigh the risks.

Early data suggests a 'cytokine storm' is involved in the PIMS-TS disease process. This proposed observational study will investigate whether children presenting to the non-ICU setting with features of PIMS-TS have raised cytokine storm biomarkers and whether these may be used to predict which children go onto develop severe disease.

The proposed study will include up to 15 hospitals across East of England. NHS clinical care teams will identify patients meeting the inclusion criteria and upload anonymised data into a secure web-based study database. Data will be retrieved for retrospective cases from 1st March 2020 and prospective data entered up until September 2021.

One hundred children presenting to acute (non-ICU) paediatric services with symptoms of PIMS-TS during the study period will be included.

The primary objective of the study is to describe the 'cytokine storm' biomarker profiles of children aged between 3 months to 16 years presenting with PIMS-TS to the non-ICU setting, focussing on those biomarkers which are readily accessible to district general hospitals (Pro-Beta Natriuretic peptide [BNP], ferritin, and CRP).

The secondary aims of the study are to:

1. Compare cytokine storm biomarker profiles of children who have a mild disease course to those who develop severe disease to identify whether there are any differences between these groups

2. Evaluate the association between cytokine storm biomarker profiles and severe events

3. Compare i) demographic characteristics (including pre-existing disease), and ii) other routine clinical investigations of children who have a mild disease course and those who develop severe disease to identify any differences between these 2 groups

4. Evaluate the association between vaccination status and disease severity

5. Compare cytokine storm biomarker profiles of children testing positive and those testing negative for SARS-CoV-2 via PCR on 2x nasopharyngeal swabs to identify any differences between these 2 groups.

Conditions

Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-Cov-2

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Within the age range of 3 months to ≤16 years
• Presenting clinically to non-ICU paediatric acute services at hospitals in the East of England region with symptoms suggestive of PIMS (e.g. incomplete Kawasaki's disease/Toxic Shock Syndrome) i.e. having: persistent fever (>38.0oC for 5 or more days) AND high CRP (>80) AND with one or more of additional features listed in Appendix 1 of the RCPCH document 'Guidance: paediatric multisystem inflammatory syndrome temporarily associated with COVID-19'
• Having either a positive or negative SARS-Cov-2 PCR test

Exclusion Criteria

• Aged below 3 months old or above 16 years old
• Confirmation of any microbial cause other than SARS-Cov-2 (including bacterial sepsis, staphylococcal or streptococcal shock syndromes, infections associated with myocarditis such as enterovirus). Determination of such microbial causes is by routine testing i.e. blood culture; pneumococcal, meningococcal, group A strep, staph aureus blood PCR; ASOT; EBV, CMV, adenovirus, enterovirus PCR on blood; urine and stool culture; throat swab culture; stool virology.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Anglia Ruskin University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jo-Anne Johnson, MRCPCH, PhD

Role: PRINCIPAL_INVESTIGATOR

Anglia Ruskin University

Locations

Mid Essex Hospital Trust

Chelmsford, Essex, United Kingdom

East Suffolk and north Essex NHS Foundation Trust

Colchester, Essex, United Kingdom

The Princess Alexandra Hospital NHS Trust

Harlow, Essex, United Kingdom

James Paget University Hospitals NHS Foundation Trust

Great Yarmouth, Norfolk, United Kingdom

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, Norfolk, United Kingdom

East Suffolk and North Essex Foundation Trust

Ipswich, Suffolk, United Kingdom

Countries

United Kingdom

Other Identifiers

19/20/048

Identifier Type: -

Identifier Source: org_study_id