A systematic review on Multisystem Inflammatory Syndrome in Children (MIS-C) with COVID-19: Development of a scoring system for clinical diagnosis

  1. Suchitra V Surve
  2. Shaini Joseph
  3. Rahul K Gajbhiye
  4. Smita D Mahale
  5. Deepak N Modi

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Abstract

Background

There is growing evidence of Multisystem Inflammatory Syndrome in Children (MIS-C) resembling Kawasaki disease in children infected with SARS-CoV-2. The review was undertaken to evaluate the case definition, the spectrum of clinical presentations and current management practices in children with COVID-19 presenting with or without MIS-C.

Methods

The individual patient data from 119 studies accounting for 333 children were analyzed. We devised a scoring system as per WHO criteria to classify the patients as MIS-C or without MIS-C. A score of 3 was given for the presence of fever (>24h) and a score of 1 for lab-confirmed diagnosis of SARS-CoV-2. Additionally, a score of 1 was given for a) rash or conjunctivitis or muco-cutaneous inflammation signs, b) hypotension or shock, c) diarrhea, vomiting or abdominal pain, d) features of myocardial dysfunction as determined by abnormal eco-cardiography or elevated Troponin or N-terminal pro B-type Natriuretic Peptide (NT-proBNP), e) evidence of coagulopathy as evidenced by elevated levels of prothrombin time PT, partial thromboplastin time PTT or D-dimer, f) laboratory evidence of inflammation as determined by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) or procalcitonin. A negative score of (−3) was given when there was a diagnosis of sepsis, staphylococcal or streptococcal shock syndrome. Based on these criteria, a minimum score of 6 was essential to classify the child as MIS-C.

Results

Based on this score, 18% (52/289) of cases were identified to be MIS-C. A greater proportion of children with MIS-C had cardiac involvement (MIS-C 80% vs Non-MIS-C 20%) and gastrointestinal involvement (MIS-C 71% vs Non-MIS-C 12%). Lymphopenia was commonly reported in MIS-C (MIS-C 54.2% vs Non-MIS-C 29.7%). In addition to routine inflammatory markers, significantly greater proportion of children with MIS-C had elevated Ferritin, LDH, Fibrinogen and IL-6. Children with MIS-C were less likely to have respiratory symptoms like cough (MIS-C 25% vs Non-MIS-C 75%) and rhinorrhea (MIS-C 4% vs Non-MIS-C 22.8%). A greater proportion of children with MIS-C required intensive care and aggressive treatment; and mortality rates were also higher in MIS-C group (MIS-C 10% vs Non-MIS-C 1%).

Conclusion

The children with COVID-19 having cardiac and/or gastrointestinal involvement are more likely to develop MIS-C. The children with MIS-C have higher mortality rates. The scoring system developed herein will aid clinicians in patient diagnosis and timely management.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.23.21255879: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search Strategy: The PubMed and Google Scholar literature database, journal databases, preprints servers and specialized resources like COVID-19 Research Database, LitCovid, CNKI database comprising of over 3900 Chinese journals were searched systematically using COVID-19 search terms: “coronavirus”, “COVID19”, “2019-nCoV”, “SARS-CoV-2”, “COVID-19”, “COVID” together with keywords commonly used to refer to pediatric population: “pediatric”, “neonate”, “newborn”, “new-born”, “infant”, “child*”, “children”.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, a major limitation of the systematic reviews is that the clinical case definition of MIS-C was as per the author criteria which vary significantly between different studies. Further, as definition of MIS-C is an evolving concept, many studies have misclassified the cases in absence of an objective criteria. To attain objectivity and uniformity across studies we first evolved a scoring system for the clinical signs of MIS-C as per WHO criteria. We gave the highest weightage to fever as it is a mandatory requirement to classify MIS-C as per WHO criteria. As not all children will present with all the symptoms, a score of 1 was given for other parameters. As septicemia can also present like MIS-C22, it is necessary to rule out sepsis in the children. A high negative score for sepsis was thus included to provide an accurate differential diagnosis of COVID-19 associated MIS-C. This scoring system was implemented on the primary data collected for 333 children and two authors accurately classified 52 children having MIS-C. Although this scoring needs to be clinically validated in a hospital setup, we believe that our scoring system is robust and can be utilized by clinicians to classify MIS-C. Overall our study estimated the prevalence of MIS-C in 21% of children with symptomatic COVID-19. We next used our scoring system to compare the presentation of 52 children with MIS-C vs 237 non-MIS-C cases. We noted that the risk of MIS-C is low (∼10%) in children with COVID-19 below ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.04.23.21255879v1 on medRxiv