Plasma Extracellular Vesicles Derived from Pediatric COVID-19 Patients Modulate Monocyte and T Cell Immune Responses Based on Disease Severity

Cetinkaya P. G., Abras I. F., Evcili I., Yildirim T., Ceylan Y., Kara Eroglu F., ...More

Immunological Investigations, vol.53, no.7, pp.1141-1175, 2024 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 53 Issue: 7
  • Publication Date: 2024
  • Doi Number: 10.1080/08820139.2024.2385992
  • Journal Name: Immunological Investigations
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1141-1175
  • Keywords: CD4+T cells, COVID-19, extracellular vesicles (EVs), immune-suppression, monocytes, programmed cell death 1 ligand (PDL1), SARS-CoV-2
  • Middle East Technical University Affiliated: Yes

Abstract

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.