Objectives. We aimed to measure SARS-CoV-2 serologic responses in children hospitalized with multisystem inflammatory syndrome (MIS-C) compared to COVID-19, Kawasaki Disease (KD) and hospitalized pediatric controls.
Methods. From March 17, 2020 – May 26, 2020, we prospectively identified hospitalized children at Children’s Healthcare of Atlanta with MIS-C (n=10), symptomatic COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike receptor binding domain (RBD) IgM and IgG, full-length spike IgG, and nucleocapsid protein antibodies by quantitative ELISAs and SARS-CoV-2 neutralizing antibodies by live-virus focus reduction neutralization assays. We statistically compared the log-transformed antibody titers among groups and performed linear regression analyses.
Results. All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated with full-length spike IgG antibodies (R2 =0.956, P<0.001), nucleocapsid protein antibodies (R2 =0.846,P<0.001), and neutralizing antibodies (R2 =0.667, P<0.001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer [GMT] 6800, 95% CI 3495-13231) than children with COVID-19 (GMT 626, 95% CI 251-1563, P<0.001), KD (GMT 124, 95% CI 91-170, P<0.001) and hospitalized controls (GMT 85, P<0.001). All children with MIS-C also had detectable RBD IgM antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with erythrocyte sedimentation rate (R2 =0.512, P<0.046) and with hospital (R2 =0.548, P=0.014) and ICU lengths of stay (R2 =0.590, P=0.010).
Conclusion. Quantitative SARS-CoV-2 serology may have a role in establishing the diagnosis of MIS-C, distinguishing it from similar clinical entities, and stratifying risk for adverse outcomes.
BACKGROUND. During the SARS‐CoV2 pandemic, there has been increase in hyperinflammatory presentation in previously healthy children with a variety of cardiac manifestations. Our objective is to describe the cardiac manifestations found in an international cohort of 55 pediatric cases with multi‐system inflammatory syndrome (MIS‐C) during the SARS‐CoV2 pandemic.
METHODS. We reviewed data on previously healthy pediatric patients (≤18 years) with structurally normal hearts who presented at hospitals in the United States, United Kingdom, Spain and Pakistan with MIS‐C and had consultation with a pediatric cardiologist. Data collected included demographics, clinical presentation, laboratory values, electrocardiographic abnormalities, echocardiographic findings and initial therapies.
RESULTS. A total of 55 patients presented with MIS‐C. Thirty‐five patients (64%) had evidence of decreased left ventricular function, 17 (31%) had valvulitis, 12 (22%) with pericardial effusion and 11 (20%) with coronary abnormalities. Twenty‐seven (49%) required ICU admission and 24 (44%) had evidence of shock. Eleven patients (20%) fulfilled complete Kawasaki disease criteria and had lower NT pro‐BNP, D‐dimer and ferritin levels compared with those who did not fulfill criteria. Electrophysiologic abnormalities occurred in 6 patients and included complete atrioventricular (AV) block, transient AV block and ventricular tachycardia.
CONCLUSIONS. We describe the first international cohort of pediatric patients with MIS‐C during the SARS‐CoV2 pandemic with a range of cardiac manifestations. This paper brings awareness and alertness to the global medical community to recognize these children during the pandemic and understand the need for early cardiology evaluation and follow‐up.
EDITOR’S NOTE: ‘ Most patients had recovery of ventricular function, but 6–14% of patients had persistent dysfunction at discharge.’
Multisystem Inflammatory Syndrome in Children (MIS-C) is a new phenomenon reported worldwide with temporal association with COVID-19. The objective of this paper is to evaluate reported cases in children and adolescents.
From 1726 papers, 35 documented papers related to MIS-C cases identified 783 individual cases of MIS-C between March-June 2020; with 55% being male (n = 435) and a median age of 8.6 years (IQR, 7–10 years; range 3 months–20 years).
Patients with MIS-C were noted to have a high frequency of gastrointestinal symptoms (71%) including abdominal pain (34%) and diarrhea (27%). Cough and respiratory distress were reported in 4.5% and 9.6% cases respectively. Blood parameters showed neutrophilia in 345/418 (83%) of cases and a high CRP in 587/626 (94%). 362/619 (59%) cases were SARS-CoV-2 infection positive (serology or PCR) however only 41% demonstrated pulmonary changes on chest imaging.
Severity of illness was high with 68% cases requiring intensive care admission; 63% requiring inotropic support; 244/783 (28%) cases needing some form of respiratory support (138 mechanically ventilated), and 31 required extra-corporeal membrane oxygenation.
Treatment strategies included intravenous immunoglobulin (63%) and intravenous steroids (44%). 29 cases received Infliximab, 47 received IL1 (interleukin) receptor antagonist, and 47 received IL6-receptor antagonist. 12/783 (1.5%) children died.
In summary, a higher incidence of gastrointestinal symptoms were noted in MIS-C. In contrast to acute COVID-19 infection in children, MIS-C appears to be a condition of higher severity with 68% of cases having required critical care support.