Friday, May 15, 2020

CDC HAN: Multisystem Inflammatory Syndrome In Children (MIS-C)


Eighteen days ago we saw the first alert issued in the UK (see PICS: NHS Alert On Possible Severe Pediatric COVID-19 Complication) on a suspected COVID-19 related illness that was hospitalizing children in serious condition.
A few days later the Royal College of Paediatrics and Child Health published a case definition and preliminary guidance on the treatment of this condition (see RCPCH: Case Definition For Pediatric Inflammatory Syndrome).
Case definition:
  1. A child presenting with persistent fever, inflammation (neutrophilia, elevated CRP and lymphopaenia) and evidence of single or multi-organ dysfunction (shock, cardiac, respiratory, renal, gastrointestinal or neurological disorder) with additional features (see listed in Appendix 1 ). This may include children fulfilling full or partial criteria for Kawasaki disease.
  2. Exclusion of any other microbial cause, including bacterial sepsis, staphylococcal or streptococcal shock syndromes, infections associated with myocarditis such as enterovirus (waiting for results of these investigations should not delay seeking expert advice).
  3. SARS-CoV-2 PCR testing may be positive or negative
(Continue . . . )
On May 4th the New York City Health department issued a State-wide HAN (Health Alert Network) message, announcing 15 suspected cases (see below).
2020 Health Alert #13:Pediatric Multi-System Inflammatory Syndrome Potentially Associated with COVID-19
  • Fifteen cases compatible with multi-system inflammatory syndrome have been identified in children in New York City hospitals.
  • Characterized by persistent fever and features of Kawasaki disease and/or toxic shock syndrome; abdominal symptoms common
  • Cases may require intensive care unit admission for cardiac and/or respiratory support Polymerase chain reaction testing for SARS-CoV-2 may be positive or negative
  • Early recognition and specialist referral are essential, including to critical care if warranted
As additional warnings have been issued, more doctors have begun reporting cases, with New York State reporting 85 cases (3 fatal)  as of four days ago.
While this is apparently a rare complication in children, it can be a serious one.  Over time we should get a better idea on just how prevalent it really is. 
Late yesterday afternoon the CDC released their own HAN - calling the condition Multisystem Inflammatory Syndrome In Children (MIS-C) - issuing their own case definition and asking doctors around the country to be alert and report cases.
Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19)
Distributed via the CDC Health Alert Network    
May 14, 2020, 4:45 PM ET      CDCHAN-00432
The Centers for Disease Control and Prevention (CDC) is providing 1) background information on several cases of a recently reported multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19); and 2) a case definition for this syndrome. CDC recommends healthcare providers report any patient who meets the case definition to local, state, and territorial health departments to enhance knowledge of risk factors, pathogenesis, clinical course, and treatment of this syndrome.
On April 26, 2020, clinicians in the United Kingdom (UK) recognized increased reports of previously healthy children presenting with a severe inflammatory syndrome with Kawasaki disease-like features.1 The cases occurred in children testing positive for current or recent infection by SARS-CoV-2, the novel coronavirus that causes COVID-19, based on reverse-transcriptase polymerase chain reaction (RT-PCR) or serologic assay, or who had an epidemiologic link to a COVID-19 case. Patients presented with a persistent fever and a constellation of symptoms including hypotension, multiorgan (e.g., cardiac, gastrointestinal, renal, hematologic, dermatologic and neurologic) involvement, and elevated inflammatory markers.2 Respiratory symptoms were not present in all cases.
Eight cases, including one death, from the UK were described in a recent publication.3 In the limited sample of 8 children, it was reported that 75% of the patients were of Afro-Caribbean descent and 62.5% were male. The report also indicated that all 8 patients tested positive for SARS-CoV-2 through antibody testing, including the patient that died.3
During March and April, cases of COVID-19 rapidly increased in New York City and New York State. In early May 2020, the New York City Department of Health and Mental Hygiene received reports of children with multisystem inflammatory syndrome. From April 16 through May 4, 2020, 15 patients aged 2-15 years were hospitalized, many requiring admission to the intensive care unit. As of May 12, 2020, the New York State Department of Health identified 102 patients (including patients from New York City) with similar presentations, many of whom tested positive for SARS-CoV-2 infection by RT-PCR or serologic assay. New York State and New York City continue to receive additional reports of suspected cases.
Additional reports of children presenting with severe inflammatory syndrome with a laboratory-confirmed case of COVID-19 or an epidemiological link to a COVID-19 case have been reported by authorities in other countries.4
It is currently unknown if multisystem inflammatory syndrome is specific to children or if it also occurs in adults.
There is limited information currently available about risk factors, pathogenesis, clinical course, and treatment for MIS-C. CDC is requesting healthcare providers report suspected cases to public health authorities to better characterize this newly recognized condition in the pediatric population.
Healthcare providers who have cared or are caring for patients younger than 21 years of age meeting MIS-C criteria should report suspected cases to their local, state, or territorial health department.
For additional information, please contact CDC’s 24-hour Emergency Operations Center at 770-488-7100. After hour phone numbers for health departments are available at the Council of State and Territorial Epidemiologists website ( icon).

Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C)
  • An individual aged < 21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (> 2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological);AND
  • No alternative plausible diagnoses; AND
  • Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms
Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
ii Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin
Additional comments
Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C
Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection