Multisystem inflammatory syndrome in children
- In April 2020 during the SARS-CoV-2 outbreak UK pediatricians alerted the National Health Service of a new systemic inflammatory condition similar to Kawasaki disease in children testing positive for the virus
- Cases were then reported worldwide with patients admitted to ICUs in the USA4,5,10, Canada10Italy11, and UK2,3
- Thought to be an immunologically mediated inflammatory syndrome associated with previous SARS-CoV-2 infection1
- Cases occur 3-5.5 weeks after patients tested positive for SARS-CoV-2
- While Kawasaki disease has a predilection for children of Asian descent, MIS-C seems to affect African American children more often9
- Compared to Kawasaki patients are generally older (median age 8.6 vs 2.5)1 and had a predominance of GI symptoms
- Patients with MIS-C are significantly more likely to present with dyspnea, vomiting, diarrhea, lymphopenia, and elevated LDH and and D-dimer compared to patients with COVID-19 without MIS-C 6
- Occurs in 2/100,000 persons under 214
- In a systematic review published June 2020, 11/7780 (0.14%) COVID-19 positive children met the CDC’s criteria for MIS-C6
- Abdominal pain
- Sore throat
- Cardiac dysfunction
- Acute kidney injury
- Kawasaki disease
- Toxic shock syndrome
- Juvenile idiopathic arthritis
- Pneumonia (Peds)
- Hemophagocytic lymphohistiocytosis
- Macrophage activation syndrome
- Rocky Mountain Spotted Fever
- Low albumin
- Inflammatory markers (elevated)
- An individual aged <21 years presenting with feveri, 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
- iFever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
- iiIncluding, 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
- 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
- Children and adolescents 0–19 years of age with fever > 3 days
- AND two of the following:
- a) Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet).
- b) Hypotension or shock.
- c) Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP),
- d) Evidence of coagulopathy (by PT, PTT, elevated d-Dimers).
- e) Acute gastrointestinal problems (diarrhoea, vomiting, or abdominal pain).
- Elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin.
- No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes.
- Evidence of COVID-19 (RT-PCR, antigen test or serology positive), or likely contact with patients with COVID-19.
- Corticosteroids (shock or risk of coronary aneurysm)1
- Antibiotics for sepsis or pneumonia
- Mechanical ventilation
- Biologics (unresponsive to IVIG and steroids)1
|'||Study||Capone et al.1||Davies et al.3||Dufort et al.4||Fields et al.5||Lee et al.7||Shekerdemian et al.10|
|Complication (%)||ICU admission||79||100%i||80||80||61||100%i|
|Invasive mechanical ventilation||18||46||10||20||0||38|
|Coronary artery abnormalities||24||36||9||8||21||N/A|
|Acute kidney injury||70||N/A||10||5||21||N/A|
iStudy contained only patients admitted to pediatric ICUs.
- Varied reports on proportion requiring ICU level of care (21-80)1,4
- NY Webinar
- Capone CA et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory disease of childhood (MIS-C) associated with SARS-CoV-2 infection. J Pediatr. 2020. (Epub ahead of print).
- Chiotos K et al. Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series. J Pediatric Infect Dis Soc. 2020;9(3):393-398.
- Davies P et al. Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicenter observational study. doi: 10.1016/S2352-4642(20)30215-7
- Dufort EM et al. Multisystem Inflammatory Syndrome in Children in New York State. N Eng J Med. 2020;383(4):347-358.
- Feldstein LR et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Eng J Med. 2020;383(4):334-346.
- Hoang et al. COVID-19 in 7780 pediatric patients: A systemic review. EClinicalMedicine. 2020;24. Accessed August 1, 2020. DOI: https://doi.org/10.1016/j.eclinm.2020.100433
- Levin M. Childhood Multisystem Inflammatory Syndrome – A New Challenge in the Pandemic. N Eng J Med. 2020;383(4):393-395.
- Lee PY et al. Distinct clinical and immunological features of SARS-COV-2-induced multisystem inflammatory syndrome in children. J Clin Invest. 2020. https://doi.org/10.1172/JCI141113
- Miller J et al. Gastrointestinal symptoms as a major presentation component of a novel multisystem inflammatory syndrome in children (MIS-C) that is related to COVID-19: a single center experience of 44 cases. Gastroenterology. 2020. (Epub ahead of print). doi: 10.1053/j.gastro.2020.05.079
- Rowley A. Understanding SARS-CoV-2 related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020;20(453-454). https://doi.org/10.1038/s41577-020-0367-5
- Shekerdemian LS et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 2020. doi:10.1001/jamapediatrics.2020.1948
- Verdoni L et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 2020; 395: 1771-8.
- Center for Disease Control and Prevention. Health Alert Network (HAN). Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). Accessed July 2020. https://emergency.cdc.gov/han/2020/han00432.asp