Retrospective Cohort Study:

A 6-month multidisciplinary follow-up and outcomes of

patients with paediatric inflammatory multisystem
syndrome (PIMS-TS) at a UK tertiary paediatric hospital.
Dr Amile Inusa
Dr Iyaad Ahsan
PIMS-TS
Paediatric Multisystem Inflammatory
Syndrome- Temporally Associated
with SARS-COV-2
A hyper inflammatory syndrome.
Presenting with persistent fever,
inflammation (elevated CRP and
lymphopaenia) with evidence of single or
multi-organ dysfunction (shock, cardiac,
—
respiratory, renal, gastrointestinal or
neurological disordeer) with additional features.
Exclusion of other microbial cause including
bacterial sepsis, staph/strep shock syndromes,
infections associated with myocarditis.
Note: COVID PCR can be positive or negative.
MIS-C

+ fever > 38 for over 24 hours

+ inflammatory markers: elevated CRP, ESR, d-dimer,
ferritin, LDH, procalcitonin, IL-6, fibrinogen/ low lymphocytes or low albumin
 https://pims-hub.org.uk/images/Cai-pics.jpg

Presentation

- FBC, film
- U&Es, LFTs,
- Glucose
- VBG and lactate
- Coagulation, Fibrinogen
- D-Dimer
- LDH, Triglyceridees
- Ferrittin, Pro BNP
- Troponin
- CK
- Vitamin D
- ASOT
- Multiple PCRs
- C
 PIMS-TS
250 cases of PIMS-TS identified in the
Paediatric Multisystem Inflammatory
Syndrome- Temporally Associated
UK from March- June 2020.
with SARS-COV-2

—
Commonest clinical features:
fever, rash, conjunctival infection, GI
symptoms.

Sometimes: Multi-organ failure > PICU.

Acute presentation understttand. What

about the long term sequelae?
Overview of Journal Article
 Methods
Study Design & Population
Aim of Study
Describe and analyse the 6 month outcomes of PIMS-TS.

Inclusion Criteria
—
• Children under 18 years
• Fulfilled RCPCH criteria for PIMS-TS
• Admission to GOSH
Exclusion Criteria

• Nil lab evidence of COVID infection (iee

positive seerology, clear link to an
infected contact, COVID NPA-PCR).
 Methods
Procedures
Background Reviews included:
1 tertiary centre: GOSH
46 children; April 4- Sept 1, 2020. 1 Echocardiogram (senior paediatric
Data analysis completed in 2021. cardiologists).
—
Review of Patients Abnormal echo? Coronary artery
aneurysm, dilation (z score >2),
Patients were seen at 2 timepoints pericardial inflammation, EF <55%,
after discharge by MDT:
visualised hyokinesis or significant
• 6 weeks valvuloplasty.
• 6 months

Procedures
Background
1 tertiary centre: GOSH
46 children; April 4- Sept 1, 2020.
Data analysis completed in 2021.
—
Review of Patients
Patients were seen at 2 timepoints
after discharge by MDT:
Methods
Reviews included:
2 Abdominal Ultrasound or CT
scans.
Abnormal scans? Inflammatory liver
changes, Hptmaospleenoomegaly,
Ileocolitis, significant peritoneal LN.

• 6 weeks
• 6 months
 Methods
Procedures
Background Reviews included:
1 tertiary centre: GOSH
46 children; April 4- Sept 1, 2020. 3 Expanded Disability Scale (Senior
Data analysis completed in 2021. Paediatric Neurologist)

— 4 6 minute walk test + manual muscle

Review of Patients test (Two Senior Physiotherapists)
Patients were seen at 2 timepoints
after discharge by MDT: 5 PedsQL 4.0 Generic Core Scales-
physical, emotional, social and school
• 6 weeks functioning.
• 6 months
6 Paediatric Index of Emotional Distress
 Methods
Procedures
Background Reviews included:
1 tertiary centre: GOSH
46 children; April 4- Sept 1, 2020. 7 Structured parent interview:
Data analysis completed in 2021.
• Did they have a concern about a
— PIMS-TS recaps anther child?
Review of Patients • Did they take any additional isolation
Patients were seen at 2 timepoints precautions beyond the current UK
after discharge by MDT: government durance?
• Did they feel that their child was
• 6 weeks vulnerable due to PIMS-TS?
• 6 months • Once available, would the parent be
willing to be vaccinated with a
COVIID-19 vaccination?
 Results
Demographics

- Age at presentation: median, 10.2 years

- Gender split: 65:35 male:female ratio
- Ethnicity split: 20:80 white: non-white patients

- Duration of symptoms before treatment: median, 7 days.

- Clinical features: nl differences between those aged 12 and
under vs those above 12 years.

- All but 2 patients were serology positive for COVID.

- Comorbidities: 4 with ASD, 2 with Sickle Cell Disease, 1 with

Asthma, 1 with T1DM, 1 with spina bifida. Note: 1 patient had ASD +SCD.
 Results
Clinical Manifestations
- Cardiac
- Echo abnormalities: 33% on 1st echo
- Echo abnormalities: 4% at 6 months: 1 patient
had underlying SCD and dilated coronaries
(showed initial improvement at 6/52 after
aspirin). 1 patient had large coronary artery
aneurysms.
- Bloods: 84% raised troponin, 86% raised BNP
initially. Normal in 100% patients at 6 months.

- Renal
- 91% had raised creatinine, proteinuria or
hypoalbuminaemia during hospital stay.
Normalised in all patients by 6 months.
- 4 (10%) had raised BP- 1 requried amlodipine.
Summary of Results

• By 6 months, systemic inflammation was resolved in all but one patient.

• 38 (90%) of 42 patients who had positive SARS-CoV-2 IgG antibodies within 6 weeks of admission remained
seropositive at 6 months.
• Echocardiograms were normal in 44 (96%) of 46 patients by 6 months
• gastrointestinal symptoms that were reported in 45 (98%) of 46 patients at onset were present in six (13%) of
46 patients at 6 months.
• Renal, haematological, and otolaryngological findings largely resolved by 6 months.
• Although minor abnormalities were identified on neurological examination in 24 (52%) of 46 patients at 6
weeks and in 18 (39%) of 46 at 6 months, we found minimal functional impairment at 6 months (median
Expanded Disability Status Scale score 0 [IQR 0–1]).
• Median manual muscle test-8 scores improved from 53 (IQR 43–64) during hospital admission to 80 (IQR 68–
80) at 6 months, but 18 (45%) of 40 patients showed 6-min walk test results below the third centile for their
age or sex at 6 months.
• PedsQL responses revealed severe emotional difficulties at 6 months (seven [18%] of 38 by parental report
and eight [22%] of 38 by self report).
• 45 (98%) of 46 patients were back in full-time education
Critical Appraisal Skill
Program Checklist
Did the study address a clearly focused issue?
Yes

• Clear population defined (<18, RCPCH diagnostic criteria for PIMS-TS, between April 4 and Sept 1, 2020)
• Aimed to describe the 6-month outcomes of PIMS-TS
• Outcomes clearly stated (few organ-specific sequelae were observed, physical re-conditioning and mental
health support remained, persisting poor exercise tolerance)
Was the cohort recruited in an acceptable way?
Yes

• Retrospective cohort study

• No need for Ethical Approval due to study design & anonymised data
• Children (aged <18)
• Fulfilled the UK RCPCH diagnostic criteria for PIMS-TS
• Admitted to Great Ormond Street Hospital (London, UK) between April 4 and Sept 1, 2020
• Patients shared the same reviews and investigations
Was the exposure accurately measured to
minimise bias??
Yes

• Fulfilled the UK RCPCH diagnostic criteria for PIMS-TS

• Comprised children (aged <18)
• Patients were subdivided into 2 groups: under 12 & over 12 to minimise
initially. However, there was no significant difference here based on age.
Was the outcome accurately measured to
reduce bias?
Yes, where possible.

• Objective measurements were used: serology, imaging,

• Furthermore, the same senior specialists reviewed the investigations ie. Echocardiograms
• The same senior specialists conducted the more subjective tests ie. Expanded Disability Status
Scale, Manual Muscle Test, 6 min Walk Test
• Structured interviews asked the same questions.
• Inclusion criteria was closely adhered to.
Have the authors identified all important
confounding factors?
No

• Difficult to note if children had bacterial illnesses or an alternative diagnosis

i.e. Kawasaki’s.
• Difficult to note from reporting if socio-economic background or general
health was a confounding variable.
Have they taken account of the confounding
factors in the design and/or analysis?
Partially

• Some children with significant medical history have their journey detailed
within the analysis.
• Larger numbers ie including other tertiary centres or capturing larger
numbers could have provided more reliable data.
• No restrictions in design, techniques, or sensitivity analysis towards
confounding factors has been mentioned
Was the follow up of subjects complete enough?
Yes.
• They included all important manifestations of PIMS-TS
within the study.

Was the follow up of subjects long enough?

Yes.
• Enough time was given to showcase the resolve of most symptoms/signs
of PIMS-TS.
• However, it was mentioned that longer-term follow-up would help define the
extended natural history of PIMS-TS.
How precise are the results??
• CI was not be applied in this study.
• Statistical Analysis was only applied to the two age groups (above 12
& under 12) with respect to neurological findings.
• Descriptive statistics summarised key clinical findings (ie lab,
radiological and key clinical results)
Do you believe the results?
Yes
• Big effect seen which is hard to ignore
• Unlikely due to bias, chance, or confounding factors
• Design and methods of study are not sufficiently flawed
Yes
• 1406 Life after PIMS-TS: A retrospective teleconsultation | Archives of
Disease in Childhood (bmj.com)
URL : https://adc.bmj.com/content/107/Suppl_2/A428.2
Can the results be applied to the local
population?
Yes

Do the results of this study fit with other

available evidence?
Yes
What are the implications of this study for
practice?
Cant Tell
• One observational study rarely provides sufficiently robust evidence to recommend
changes to clinical practice.
• Recommendations that patients recovering from PIMS-TS should be followed up so
that recovery back to baseline can be established. They may need ongoing support and
rehabilitation.
• Reassuring however that a vast majority of children improved clinically.