Frontiers in Pediatrics (Jun 2022)

Myeloid-Derived Suppressor Cells and Clinical Outcomes in Children With COVID-19

  • Katherine Bline,
  • Katherine Bline,
  • Angel Andrews,
  • Melissa Moore-Clingenpeel,
  • Sara Mertz,
  • Fang Ye,
  • Victoria Best,
  • Rouba Sayegh,
  • Cristina Tomatis-Souverbielle,
  • Cristina Tomatis-Souverbielle,
  • Ana M. Quintero,
  • Zachary Maynard,
  • Rebecca Glowinski,
  • Asuncion Mejias,
  • Asuncion Mejias,
  • Octavio Ramilo,
  • Octavio Ramilo

DOI
https://doi.org/10.3389/fped.2022.893045
Journal volume & issue
Vol. 10

Abstract

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BackgroundAlthough children with COVID-19 account for fewer hospitalizations than adults, many develop severe disease requiring intensive care treatment. Critical illness due to COVID-19 has been associated with lymphopenia and functional immune suppression. Myeloid-derived suppressor cells (MDSCs) potently suppress T cells and are significantly increased in adults with severe COVID-19. The role of MDSCs in the immune response of children with COVID-19 is unknown.AimsWe hypothesized that children with severe COVID-19 will have expansion of MDSC populations compared to those with milder disease, and that higher proportions of MDSCs will correlate with clinical outcomes.MethodsWe conducted a prospective, observational study on a convenience sample of children hospitalized with PCR-confirmed COVID-19 and pre-pandemic, uninfected healthy controls (HC). Blood samples were obtained within 48 h of admission and analyzed for MDSCs, T cells, and natural killer (NK) cells by flow cytometry. Demographic information and clinical outcomes were obtained from the electronic medical record and a dedicated survey built for this study.ResultsFifty children admitted to the hospital were enrolled; 28 diagnosed with symptomatic COVID-19 (10 requiring ICU admission) and 22 detected by universal screening (6 requiring ICU admission). We found that children with severe COVID-19 had a significantly higher percentage of MDSCs than those admitted to the ward and uninfected healthy controls. Increased percentages of MDSCs in peripheral blood mononuclear cells (PBMC) were associated with CD4+ T cell lymphopenia. MDSC expansion was associated with longer hospitalizations and need for respiratory support in children admitted with acute COVID-19.ConclusionThese findings suggest that MDSCs are part of the dysregulated immune responses observed in children with severe COVID-19 and may play a role in disease pathogenesis. Future mechanistic studies are required to further understand the function of MDSCs in the setting of SARS-CoV-2 infection in children.

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