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Plasma Extracellular Vesicles Derived from Pediatric COVID-19 Patients Modulate Monocyte and T Cell Immune Responses
Pınar Gur Cetinkaya1, Irem Fatma Abras1, Irem Evcili1
1Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.
Insights
Extracellular vesicles (EVs) from severe COVID-19 patients suppressed immune responses in healthy cells. These plasma-derived EVs may play a role in early immunosuppression during severe pediatric COVID-19.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- The COVID-19 pandemic has led to significant global morbidity and mortality.
- The specific role of plasma-derived extracellular vesicles (EVs) in pediatric COVID-19 patients is not well understood.
Purpose of the Study:
- To investigate the impact of plasma-derived EVs from pediatric COVID-19 patients on immune cell function.
- To explore the relationship between COVID-19 severity and immune responses mediated by EVs.
Main Methods:
- Extracellular vesicles (EVs) were isolated from healthy controls and pediatric COVID-19 patients with varying disease severity.
- In vitro assays, flow cytometry, and ELISA were used to assess EV effects on healthy peripheral blood mononuclear cells (PBMCs), naïve CD4+ T cells, and monocytes.
Main Results:
- Severe acute COVID-19 cases showed increased cytokines, decreased IFNγ, and lower CD4+ T cell and monocyte counts, indicating immunosuppression.
- EVs from severe acute patients stimulated healthy cells to increase PD-L1 expression, promote Th2 and Treg cells, reduce IFNγ, and alter Th1/Th17 ratios.
- Patient-derived EVs significantly reduced proinflammatory cytokine production by monocytes and decreased CD4+ T cell and monocyte populations in stimulated healthy PBMCs.
Conclusions:
- COVID-19 severity correlates with distinct immunological responses and EV-mediated effects.
- Plasma-derived EVs may contribute to early-stage immunosuppression in severe COVID-19 patients.
Background:
The COVID-19 pandemic has caused significant morbidity and mortality globally. The role of plasma-derived extracellular vesicles (EVs) in pediatric COVID-19 patients remains unclear.
Methods:
We isolated EVs from healthy controls (n = 13) and pediatric COVID-19 patients (n = 104) with varying severity during acute and convalescent phases using serial ultracentrifugation. EV effects on healthy PBMCs, naïve CD4+ T cells, and monocytes were assessed through in vitro assays, flow cytometry, and ELISA.
Results:
Our findings indicate that COVID-19 severity correlates with diverse immune responses. Severe acute cases exhibited increased cytokine levels, decreased IFNγ levels, and lower CD4+ T cell and monocyte counts, suggesting immunosuppression. EVs from severe acute patients stimulated healthy cells to express higher PDL1, increased Th2 and Treg cells, reduced IFNγ secretion, and altered Th1/Th17 ratios. Patient-derived EVs significantly reduced proinflammatory cytokine production by monocytes (p < .001 for mild, p = .0025 for severe cases) and decreased CD4+ T cell (p = .043) and monocyte (p = .033) populations in stimulated healthy PBMCs.
Conclusion:
This study reveals the complex relationship between immunological responses and EV-mediated effects, emphasizing the impact of COVID-19 severity. We highlight the potential role of plasma-derived EVs in early-stage immunosuppression in severe COVID-19 patients.
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