APA
Click to copy
Song, N.-J., Allen, C., Vilgelm, A., Riesenberg, B., Weller, K., Reynolds, K., … Li, Z. (2021). TREATMENT WITH SOLUBLE CD24 ATTENUATES COVID-19-ASSOCIATED SYSTEMIC IMMUNOPATHOLOGY. MedRxiv.
Chicago/Turabian
Click to copy
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.” medRxiv (2021).
MLA
Click to copy
Song, No-Joon, et al. “TREATMENT WITH SOLUBLE CD24 ATTENUATES COVID-19-ASSOCIATED SYSTEMIC IMMUNOPATHOLOGY.” MedRxiv, 2021.
BibTeX Click to copy
@article{no-joon2021a,
title = {TREATMENT WITH SOLUBLE CD24 ATTENUATES COVID-19-ASSOCIATED SYSTEMIC IMMUNOPATHOLOGY},
year = {2021},
journal = {medRxiv},
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. SARS-CoV-2 causes COVID-19 through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns (DAMPs) and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) is able to blunt the broad inflammatory response induced by DAMPs in multiple models. A recent randomized phase III trial evaluating the impact of CD24Fc in patients with severe COVID-19 demonstrated encouraging clinical efficacy. METHODS. We studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial (NCT04317040) collected before and after treatment with CD24Fc or placebo. We performed high dimensional spectral flow cytometry analysis of peripheral blood mononuclear cells and measured the levels of a broad array of cytokines and chemokines. A systems analytical approach was used to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. FINDINGS. 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 systemic hyper-activation of multiple cellular compartments in the placebo group, including CD8+ T cells, CD4+ T cells, and CD56+ NK cells. By contrast, CD24Fc-treated patients demonstrated blunted systemic inflammation, with a return to homeostasis in both NK and T cells within days without compromising the ability of patients to mount an effective anti-Spike protein antibody response. A single dose of CD24Fc significantly attenuated induction of the systemic cytokine response, including expression of IL-10 and IL-15, and diminished the coexpression and network connectivity among extensive circulating inflammatory cytokines, the parameters associated with COVID-19 disease severity. INTERPRETATION. Our data demonstrates that CD24Fc treatment 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. FUNDING. NIH