APA
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Song, N.-J., Allen, C., Vilgelm, A., Riesenberg, B., Weller, K., Reynolds, K., … Li, Z. (2022). Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology. Journal of Hematology &Amp; Oncology.
Chicago/Turabian
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Song, No-Joon, Carter Allen, A. Vilgelm, B. Riesenberg, K. Weller, Kelsi Reynolds, K. Chakravarthy, et al. “Treatment with Soluble CD24 Attenuates COVID-19-Associated Systemic Immunopathology.” Journal of Hematology & Oncology (2022).
MLA
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Song, No-Joon, et al. “Treatment with Soluble CD24 Attenuates COVID-19-Associated Systemic Immunopathology.” Journal of Hematology &Amp; Oncology, 2022.
BibTeX Click to copy
@article{no-joon2022a,
title = {Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology},
year = {2022},
journal = {Journal of Hematology & Oncology},
author = {Song, No-Joon and Allen, Carter and Vilgelm, A. and Riesenberg, B. and Weller, K. and Reynolds, Kelsi and Chakravarthy, K. and Kumar, Amrendra and Khatiwada, A. and Sun, Zequn and Ma, Anjun and Chang, Yuzhou and Yusuf, Mohamed and Li, Anqi and Zeng, C. and Evans, J. and Bucci, D. and Gunasena, M. and Xu, Menglin and Liyanage, N. P. and Bolyard, C. and Velegraki, M. and Liu, Shan-Lu and Ma, Qin and Devenport, M. and Liu, Yang and Zheng, P. and Malvestutto, C. and Chung, Dongjun and Li, Zihai}
}
Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) blunts the broad inflammatory response induced by damage-associated molecular patterns via binding to extracellular high mobility group box 1 and heat shock proteins, as well as regulating the downstream Siglec10-Src homology 2 domain–containing phosphatase 1 pathway. A recent randomized phase III trial evaluating CD24Fc for patients with severe COVID-19 (SAC-COVID; NCT04317040) demonstrated encouraging clinical efficacy. Methods Using a systems analytical approach, we studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial to discern the impact of CD24Fc treatment on immune homeostasis. We performed high dimensional spectral flow cytometry and measured the levels of a broad array of cytokines and chemokines to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. Results Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found that patients with severe COVID-19 had systemic hyper-activation of multiple cellular compartments, including CD8 + T cells, CD4 + T cells, and CD56 + natural killer cells. Treatment with CD24Fc blunted this systemic inflammation, inducing a return to homeostasis in NK and T cells without compromising the anti-Spike protein antibody response. CD24Fc significantly attenuated the systemic cytokine response and diminished the cytokine coexpression and network connectivity linked with COVID-19 severity and pathogenesis. Conclusions Our data demonstrate that CD24Fc rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19.
