Pediatric EVALI in the Age of COVID-19/MIS-C: Diagnostic Considerations

Abstract

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) and e-cigarette or vaping product use-associated lung injury (EVALI) have significant overlap in clinical features, which can contribute to delay in identification and treatment. The objectives of this report were to identify and describe features that are common in both diagnoses and those that may help distinguish EVALI from MIS-C, and to highlight the diagnostic challenges observed at our tertiary medical center. METHODS: We identified adolescents diagnosed with MIS-C who had respiratory or gastrointestinal symptoms and patients diagnosed with EVALI during the same time period. We compared demographics, history, clinical manifestations, laboratory findings, and features of the hospital course to determine areas of overlap between MIS-C and EVALI, as well as distinct features of each diagnosis. Mann–Whitney U test was used to compare continuous variables and Fisher’s exact test was used to compare categorical variables. RESULTS: We found that cardiovascular and mucocutaneous findings and thrombocytopenia were more common in MIS-C. EVALI patients had a higher degree of inflammation and history of antecedent weight loss. Providers at our institution were more likely to consider MIS-C than EVALI on the differential diagnosis, including in patients with vaping history and no evidence of previous severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS: This study emphasizes the need for a thorough collection of substance use history for all patients and consideration of EVALI in adolescents who present with respiratory compromise or gastrointestinal symptoms and systemic inflammation, particularly in the absence of severe acute respiratory syndrome coronavirus 2 exposure or cardiac findings characteristic of MIS-C.

Plasma Cell-free RNA Signatures of Inflammatory Syndromes in Children

“…The final diagnosis was bacterial infection, which was the second ranked prediction by the cfRNA model. Interestingly, the patient presented with some symptoms characteristic of MIS-C, the apparently erroneous top prediction made by the cfRNA model; specifically with severe thrombocytopenia and elevated CRP, which are part of the MIS-C case definition 25 .…”

“…To test the ability of cfRNA profiles to distinguish among pediatric inflammatory syndromes, we compared cfRNA profiles for patients diagnosed with KD and MIS-C, conditions that are very similar clinically. There is a need for improved molecular tools to discriminate between these two conditions as exemplified by a recent study from Day-Lewis et al which reported significant overlap in signs and symptoms between KD and MIS-C (based on the 2023 case definition), with an estimated false positive rate of 8% 25 . The cfRNA signature presented here has near-perfect accuracy and therefore has high potential for translation into a useful clinical molecular test.…”