Identification of Early Features to Differentiate Hospitalized Children Admitted for Suspected MIS-C from Alternative Diagnoses

Background. Multi-system inflammatory syndrome in children (MIS-C) is a rare consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MIS-C shares features with common infectious and inflammatory syndromes and differentiation early in the course is difficult. Identification of early features specific to MIS-C may lead to faster diagnosis and treatment. We aimed to determine clinical, laboratory, and cardiac features distinguishing MIS-C patients within the first 24 hours of admission to the hospital from those who present with similar features but ultimately diagnosed with an alternative etiology. Methods. We performed retrospective chart reviews of children (0-20 years) who were admitted to Vanderbilt Children's Hospital and evaluated under our institutional MIS-C algorithm between June 10, 2020-April 8, 2021. Subjects were identified by review of infectious disease (ID) consults during the study period as all children with possible MIS-C require an ID consult per our institutional algorithm. Clinical, lab, and cardiac characteristics were compared between children with and without MIS-C. The diagnosis of MIS-C was determined by the treating team and available consultants. P-values were calculated using two-sample t-tests allowing unequal variances for continuous and Pearson's chi-squared test for categorical variables, alpha set at < 0.05. Results. There were 128 children admitted with concern for MIS-C. Of these, 45 (35.2%) were diagnosed with MIS-C and 83 (64.8%) were not. Patients with MIS-C had significantly higher rates of SARS-CoV-2 exposure, hypotension, conjunctival injection, abdominal pain, and abnormal cardiac exam (Table 1). Laboratory evaluation showed that patients with MIS-C had lower platelet count, lymphocyte count and sodium level, with higher c-reactive protein, fibrinogen, B-type natriuretic peptide, and neutrophil percentage (Table 2). Patients with MIS-C also had lower ejection fraction and were more likely to have abnormal electrocardiogram. Conclusion. We identified early features that differed between patients with MIS-C from those without. Development of a diagnostic prediction model based on these early distinguishing features is currently in progress.

Comparison of Demographics and Clinical Characteristics of Multisystem Inflammatory Syndrome in Children and Kawasaki Disease

Background. Multisystem inflammatory syndrome in children (MIS-C) is an illness associated with recent SARS-CoV-2 infection or exposure. Kawasaki disease (KD), a vasculitis with an unknown etiology, has overlapping clinical presentation with MIS-C, making it difficult to clinicians for distinguish between them. Therefore, we aimed to compare demographic, laboratory, and clinical characteristics between MIS-C and KD in hospitalized children in Nashville, TN. Methods. We conducted a single-center retrospective chart review for hospitalized children under 18 years who met American Heart Association criteria for KD and were treated with intravenous immunoglobulin from May 2000 to December 2019, and children meeting the CDC criteria for MIS-C from July 2020 to May 2021. Data ion for patients' demographics, clinical presentation, laboratory values and imaging results was performed. Pearson's chi-squared test for categorical variables and Wilcoxon rank sum test for continuous variables, with alpha=5%, were used to compare groups. Results. A total of 603 KD and 52 MIS-C hospitalized patients were included. Children with MIS-C were older than those with KD. A higher frequency of male sex was noted in both groups, with no significant differences in race and ethnicity (Table). MIS-C children frequently presented with symptoms similar to KD (63.5% rash, 55.8% conjunctivitis, 28.9% mucous membrane changes);however, only one MIS-C patient met criteria for complete KD (Figure). Both MIS-C and KD children presented with elevated CRP and ESR, but the median value of CRP in MIS-C children was significantly higher (Table). In addition, white cell count was lower in MIS-C children, which is primarily driven by the lower absolute lymphocyte count in this group (0.9 vs 2.7, p< 0.001), and echocardiography was more likely to be abnormal at presentation compared to KD (Table). Conclusion. MIS-C and KD present similarly in children;however, age, laboratory and echocardiography findings can help differentiate between them. Different laboratory values suggest different pathophysiology and inflammatory mediators behind these two illnesses, warranting further research.

Impaired coronary flow reserve in athletes with long-term cardiovascular symptoms after COVID-19

Introduction: Cardiovascular symptoms post-acute sequelae of SARS-CoV-2 infection (CV-PASC) have been increasingly recognized, but the underlying pathobiology is unclear. Endothelial and cardiac pericyte ACE2 receptors are important targets of SARS-CoV-2, resulting in virally-induced endothelial activation, which may adversely affect the coronary microvasculature and impair myocardial performance. We hypothesized that athletes with CV-PASC have microvascular and subclinical myocardial dysfunction. Methods: We compared 15 athletes with CV-PASC with 7 control athletes without prior COVID-19 using regadenoson stress cardiac magnetic resonance (CMR). All athletes participated in >6 hours of endurance activities per week. We analyzed CMR volumes, function, global circumferential strain (GCS), late gadolinium enhancement (LGE), and coronary flow reserve (CFR) by coronary sinus method. Values presented as median [IQR]. Results: CMR in CV-PASC athletes occurred 102 [66,123] days post-SARS-CoV-2 infection. There were no differences in chamber volumes, function, or LGE between groups. One CV-PASC athlete had acute myocarditis (7%). CVPASC athletes had decreased CFR compared with control athletes (Figure 1). Multiple CV-PASC participants had CFR below the 95% CI of the controls and reported normal values from the literature (2.9 and 2.5, respectively). GCS was worse in CV-PASC athletes at the base (-23.7% [-21.6,-26.4] vs -31.1% [-27.3,-33.0], p=0.01), mid-LV (-21.5% [-18.5,-22.8] vs -28.5 [-25.4,-29.9], p=0.008), and apex (-27.1% [-24.1,-29.9] vs -30.6% [-27.8,-38], p=0.07), though the apex did not reach statistical significance. Conclusions: This pilot case-control study found CV-PASC athletes had reduced CFR and associated subclinical myocardial dysfunction as assessed by GCS compared to control athletes. These findings suggest coronary microvascular dysfunction related to endothelial injury may mediate CV-PASC symptoms.