Paediatric Inflammatory Multisystem Syndrome During COVID-19 Pandemic
Condition: Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-Cov-2
MeSH terms: COVID-19; Syndrome
Study type: Observational

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.
    

Observational model: Case-Only
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Children (aged 3 months to ≤ 16 years) presenting to acute paediatric services (non-ICU)
        with symptoms of PIMS during the period of the COVID-19 pandemic
      
Keywords: cytokine storm; biomarkers; PIMS-TS; children; COVID-19