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Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic

Our take —

Emerging evidence suggests a multisystem inflammatory syndrome in children infected with SARS-CoV-2 that can cause critical illness. However, overall risks of severe illness and mortality in pediatric cases of COVID-19 remain low compared to those in adults. This case series highlights heart failure as one of a cluster of symptoms (including skin rash, conjunctivitis, and adenopathy) related to a severe inflammatory state. Patients were treated with immune globulin with apparently beneficial results.

Study design

Case Series

Study population and setting

This study included 35 children aged 1-16 years (median age 10, 51% male) who were admitted to 12 intensive care units in France and one in Switzerland between March 22 and April 30, 2020 with fever, cardiogenic shock or left ventricular dysfunction, and an acute inflammatory state (c-reactive protein>100 mg/L). Six (17%) patients were overweight; no patients had underlying cardiac disease.

Summary of Main Findings

SARS-CoV-2 infection was confirmed in 31/35 (89%) patients via PCR or antibody assay; 30/35 had positive antibody tests and 12 (34%) had a positive nasopharyngeal swab PCR. The median time between symptom onset and heart failure symptoms was 6 days; 29/35 (83%) were admitted directly to the ICU. Gastrointestinal symptoms were present in 29 (83%) patients, but chest pain was less common (n=6, 17%). No patients met the clinical criteria for Kawasaki disease, though several symptoms typically seen in Kawasaki disease were common: conjunctivitis (89%), cervical lymphadenopathy (60%), skin rash (57%), red/cracked lips (54%), and meningism (31%). At the time of ICU admission, 80% of patients met criteria for cardiogenic shock, 62% required mechanical ventilation and 28% required extracorporeal membrane oxygenation (ECMO). Patients had high concentrations of IL-6 and D-dimer, indicative of a severe inflammatory state. The left ventricular ejection fraction was below 30% in 10/35 (29%) of patients. 28/35 (80%) patients required inotropic support and all patients received immune globulin intravenously. Left ventricular function was fully restored in 25/35 (71%) of patients by a median of 2 days after admission. There were no fatalities and no thrombotic or embolic events; only 7/35 (20%) patients remained hospitalized by the end of follow-up.

Study Strengths

There was in-depth evaluation of cardiac functioning and longitudinal follow-up of critically ill patients.

Limitations

The timing of inflammatory syndrome and heart failure relative to SARS-CoV-2 infection is unclear; some patients may have been infected many days before hospital admission, as evidenced by the high proportion of positive antibody tests and low proportion of positive PCR results from nasopharyngeal swabs. Follow-up was incomplete (20% of patients remained hospitalized) and outcomes may change.

Value added

This study adds data on heart failure to the rapidly emerging literature on an inflammatory syndrome related to SARS-CoV-2 infection in children.