Saturday, May 16, 2020

ECDC Rapid Risk Assessment On Paediatric Inflammatory Multisystem Syndrome













#15,264

Nineteen days ago we saw the first alert go out - issued by the UK's NHS - on a newly recognized inflammatory syndrome in children which as been tentatively and temporally linked to COVID-19 (see PICS: NHS Alert On Possible Severe Pediatric COVID-19 Complication).   

Since then we've seen a barrage of reports - both in the UK and in the United States - including:
RCPCH: Case Definition For Pediatric Inflammatory Syndrome
NYC HAN Alert On Pediatric Multi-System Inflammatory Syndrome
New York DOH Advisory On Pediatric Multi-System Inflammatory Syndrome
Update On Pediatric Multi-System Inflammatory Syndrome
Late Thursday afternoon the CDC released their own HAN Advisory (see CDC HAN: Multisystem Inflammatory Syndrome In Children (MIS-C)), instructing doctors across the nation on how recognize and report the condition.
For now, this appears to be a rare complication of COVID-19 in children, but awareness and reporting are just ramping up.  
Yesterday the ECDC published their first RRA (Rapid Risk Assessment) of this syndrome in an 18-page PFD Report.  Somewhat confusingly, it has been dubbed Multisystem Inflammatory Syndrome In Children (MIS-C) by the CDC, while the ECDC is calling it Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS).
The ECDC is currently reporting about 230 suspected cases in the EU/EAA and UK in 2020, including two fatalities.  Given that New York State (pop 20 million) alone has identified 102 suspected cases, this number is likely to rise. 
For now, the ECDC appears to be taking a conservative approach - using the Bradford Hill causality criteria - they find the evidence linking COVID-19 to this syndrome to be less than robust. They write:
After assessing the evidence and rating it (limited to substantial), only five out of nine criteria would support a causal relationship between SARS-CoV-2 infection and the development of PIMS-TS. Future clinical, epidemiological and experimental studies may elucidate the biological determinants of this syndrome and further explore the evidence supporting these causality criteria.
 The Executive summary follows, along with a link to the full report.

Rapid risk assessment: Paediatric inflammatory multisystem syndrome and SARS -CoV-2 infection in children
Risk assessment
15 May 2020
Several countries affected by the coronavirus disease (COVID-19) pandemic recently reported cases of children that were hospitalised in intensive care due to a rare paediatric inflammatory multisystem syndrome (PIMS). The presenting signs and symptoms are a mix of the ones for Kawasaki disease (KD) and toxic shock syndrome (TSS) and are characterised, among others, by fever, abdominal pain and cardiac involvement. A possible temporal association with SARS-COV-2 infection has been hypothesised because some of the children that were tested for SARS-CoV-2 infection were either positive by polymerase chain reaction (PCR) or serology.
Executive summary
In total, about 230 suspected cases of this new paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) have been reported in EU/EEA countries and the UK in 2020, including two fatalities, one in the UK and one in France. These cases are being further investigated. So far, epidemiological studies have shown that children appear to be less affected by COVID-19. Only 2.1% of all laboratory-confirmed COVID-19 cases reported to The European Surveillance System (TESSy) were in the age group between 0 and 14 years of age.
To date, an association between SARS-CoV-2 infection and this new clinical entity of multisystem inflammation has not yet been established, although an association appears plausible. At current, the risk is assessed as follows:
  • The overall risk of COVID-19 in children in the EU/EEA and UK is currently considered low, based on a low probability of COVID-19 in children and a moderate impact of such disease.
  • The overall risk of PIMS-TS in children in the EU/EEA and the UK – is considered low, based on a very low probability of PIMS-TS in children and a high impact of such disease.
While the clinical management of these children has absolute priority, data collection from EU/EEA Member States and the UK would strengthen the body of knowledge for this rare condition and allow for a better analysis of these cases. An analysis of surveillance data could clarify the incidence of KD/PIMS and identify the most affected age groups and risk factors for both conditions.
ECDC has agreed with the EU/EAA Member States and the UK to include PIMS as a possible complication to be reported for EU-level COVID-19 surveillance. Research efforts should aim at a) determining the role of SARS-CoV-2 in the pathogenesis of PIMS-TS and b) answering other significant remaining questions.
Risk communication is needed to raise awareness in the medical community about PIMS-TS and inform parents and caregivers about signs and symptoms. The importance of timely contact with a healthcare worker should be stressed. Risk communication should emphasise that PIMS-TS is a rare condition and that its potential link with COVID-19 is neither established nor well understood.
Download
Rapid risk assessment: Paediatric inflammatory multisystem syndrome and SARS -CoV-2 infection in children - EN - [PDF-862.24 KB]

While the evidence of causality remains limited, in the short history of the COVID-19 pandemic, SARS-CoV-2 has consistently proven itself to be an overachiever.  It is not - as was first surmised - just a respiratory virus (see below). 
EID Journal: Two Reports On Thrombotic Events In COVID-19 Patients
JAMA: Neurologic Manifestations Of Patients With Severe Coronavirus Disease
EID Journal: Pulmonary Embolism and Increased Levels of d-Dimer in COVID-19 Patients
Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

Given this history, we should expect more surprises in the weeks and months ahead.