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

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.

KEYWORDS:

• CD4+T cells
• COVID-19
• extracellular vesicles (EVs)
• immune-suppression
• monocytes
• programmed cell death 1 ligand (PDL1)
• SARS-CoV-2

Acknowledgments

We sincerely thank Birsen Yaman, GultenEhliz, Birsen Özer, Fernuse Dereli and Sule ToksoyDemiryilmaz for their support in the collection of blood samples.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/08820139.2024.2385992.

The research ethics committee (REC) reference number

GO 22/77

Additional information

Funding

This research was partially funded by Scientific and Technological Research Council of Türkiye [SBAG-115S837, SBAG-116S602 to IG]. All authors approve the final version of the manuscript. The study was performed in accordance with the protocol approved by the local ethical committee of Hacettepe University.