Browsing by keyword "MIS-C"
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COVID-19 Pediatric DermatologyChildren are a unique subset of patients in relation to the COVID-19 pandemic, often presenting asymptomatically, mildly, or atypically. Manifestations of the skin may be a primary (or the only) presenting sign. Recognizing cutaneous manifestations of COVID-19 in the pediatric population is important to guiding precautions, testing, and management for patients and close contacts. Whereas some dermatologic signs in children overlap with those in adults, other skin findings are reported with higher frequency in children and may be clues to multisystemic sequelae. This article describes presentation, pathophysiologic theories, and management strategies for cutaneous manifestations of COVID-19 in children.
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Disease Tolerance, Epigenetic Inheritance, and Surviving Pathogenic Viral InfectionsHealth is often defined in terms of absence of disease or pathological processes, but this is a definition of exclusion and incomplete. For example, SARS-CoV-2 viral load does not reliably predict disease severity, and so individuals must vary in their ability to control inflammation and maintain normal tissue homeostasis. This host defense strategy is called disease tolerance, and better understanding of disease tolerance mechanisms could change the way that we treat disease and work to maintain health. The first project presented in this dissertation found that after accounting for effects of age and sex, innate lymphoid cells (ILCs), but not T cells, were lower in adults and children sick with COVID-19 or MIS-C, independent of lymphopenia. Furthermore, abundance of ILCs, but not of T cells, correlated inversely with disease severity. These blood ILCs were shown to produce amphiregulin, a protein implicated in disease tolerance and tissue homeostasis, and the percentage of amphiregulin-producing ILCs was lower in males. These results suggest that, by promoting disease tolerance, homeostatic ILCs decrease morbidity and mortality associated with SARS-CoV-2 infection, and that lower ILC abundance accounts for increased COVID-19 severity with age and in males. The second project describes a novel mouse model of epigenetic inheritance wherein paternal influenza A virus (IAV) infection results in less severe influenza disease in IAV infected offspring. This offspring phenotype was not attributable to differences in viral load, indicating a possible difference in disease tolerance. Paternal caloric deprivation decreased, and influenza B virus infection increased, offspring influenza disease severity, and in vitro fertilization demonstrated sperm are sufficient to transfer IAV-associated epigenetic inheritance phenotypes. These findings represent a foundation for further work that, by continuing to elucidate the mechanisms of disease tolerance and epigenetic inheritance, could provide novel therapeutic interventions to help promote and maintain health.