Myeloid-Derived Suppressor Cells and Clinical Outcomes in Children With COVID-19
Katherine Bline1,2, Angel Andrews1, Melissa Moore-Clingenpeel2
1Center for Vaccines and Immunity, Nationwide Children's Hospital, Columbus, OH, United States.
Insights
Myeloid-derived suppressor cells (MDSCs) are elevated in children with severe COVID-19, correlating with poorer outcomes like longer hospital stays and need for respiratory support. This suggests MDSCs contribute to severe COVID-19 in pediatric patients.
Area of Science:
- Pediatric Immunology
- Infectious Diseases
- Critical Care Medicine
Background:
- COVID-19 can cause severe illness in children, linked to immune suppression.
- Myeloid-derived suppressor cells (MDSCs) are implicated in severe COVID-19 in adults.
- The role of MDSCs in pediatric COVID-19 immune responses remains unclear.
Purpose of the Study:
- To investigate the presence and role of MDSCs in children hospitalized with COVID-19.
- To compare MDSC levels in severe vs. mild pediatric COVID-19 cases and healthy controls.
- To correlate MDSC proportions with clinical outcomes in pediatric COVID-19 patients.
Main Methods:
- Prospective observational study of hospitalized children with confirmed COVID-19 and healthy controls.
- Flow cytometry analysis of blood samples for MDSCs, T cells, and NK cells.
- Collection of demographic and clinical data from electronic health records and surveys.
Main Results:
- Children with severe COVID-19 exhibited significantly higher percentages of MDSCs compared to mild cases and healthy controls.
- Elevated MDSC percentages in peripheral blood mononuclear cells (PBMCs) were associated with CD4+ T cell lymphopenia.
- MDSC expansion correlated with prolonged hospitalizations and the need for respiratory support in pediatric COVID-19 patients.
Conclusions:
- MDSCs are involved in the immune dysregulation observed in severe pediatric COVID-19.
- MDSCs may play a role in the pathogenesis of severe COVID-19 in children.
- Further research is needed to elucidate the functional role of MDSCs in pediatric SARS-CoV-2 infection.
Background:
Although 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.
Aims:
We 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.
Methods:
We 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.
Results:
Fifty 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.
Conclusion:
These 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.
More Related Videos
Related Concept Videos
01:15Differentiation of Common Myeloid Progenitor Cells
01:01Regulation of Hematopoietic Stem Cells