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Song NJ, Allen C, Vilgelm AE, et al. Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology. J Hematol Oncol. 2022;15(1):5doi: 10.1186/s13045-021-01222-y.
Song, N. J., Allen, C., Vilgelm, A. E., Riesenberg, B. P., Weller, K. P., Reynolds, K., Chakravarthy, K. B., Kumar, A., Khatiwada, A., Sun, Z., Ma, A., Chang, Y., Yusuf, M., Li, A., Zeng, C., Evans, J. P., Bucci, D., Gunasena, M., Xu, M., Liyanage, N. P. M., Bolyard, C., Velegraki, M., Liu, S. L., Ma, Q., Devenport, M., Liu, Y., Zheng, P., Malvestutto, C. D., Chung, D., & Li, Z. (2022). Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology. Journal of hematology & oncology, 15(1), 5. https://doi.org/10.1186/s13045-021-01222-y
Song, No-Joon, et al. "Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology." Journal of hematology & oncology vol. 15,1 (2022): 5. doi: https://doi.org/10.1186/s13045-021-01222-y
Song NJ, Allen C, Vilgelm AE, Riesenberg BP, Weller KP, Reynolds K, Chakravarthy KB, Kumar A, Khatiwada A, Sun Z, Ma A, Chang Y, Yusuf M, Li A, Zeng C, Evans JP, Bucci D, Gunasena M, Xu M, Liyanage NPM, Bolyard C, Velegraki M, Liu SL, Ma Q, Devenport M, Liu Y, Zheng P, Malvestutto CD, Chung D, Li Z. Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology. J Hematol Oncol. 2022 Jan 10;15(1):5. doi: 10.1186/s13045-021-01222-y. PMID: 35012610.
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J Hematol Oncol. 2022 Jan 10;15(1):5. doi: 10.1186/s13045-021-01222-y.

Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology.

Journal of hematology & oncology

No-Joon Song, Carter Allen, Anna E Vilgelm, Brian P Riesenberg, Kevin P Weller, Kelsi Reynolds, Karthik B Chakravarthy, Amrendra Kumar, Aastha Khatiwada, Zequn Sun, Anjun Ma, Yuzhou Chang, Mohamed Yusuf, Anqi Li, Cong Zeng, John P Evans, Donna Bucci, Manuja Gunasena, Menglin Xu, Namal P M Liyanage, Chelsea Bolyard, Maria Velegraki, Shan-Lu Liu, Qin Ma, Martin Devenport, Yang Liu, Pan Zheng, Carlos D Malvestutto, Dongjun Chung, Zihai Li

Affiliations

  1. The Pelotonia Institute for Immuno-Oncology, The Ohio State University James Comprehensive Cancer Center, 460 W. 12th Ave, Columbus, OH, 43210, USA.
  2. Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA.
  3. Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA.
  4. The Ohio State University College of Medicine, Columbus, OH, USA.
  5. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
  6. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
  7. Center for Retrovirus Research and Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
  8. Department of Microbial Infection and Immunity, The Ohio State University College of Medicine, Columbus, OH, USA.
  9. Department of Veterinary Biosciences, The Ohio State University College of Veterinary Medicine, Columbus, OH, USA.
  10. Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.
  11. OncoC4, Rockville, MD, USA.
  12. The Pelotonia Institute for Immuno-Oncology, The Ohio State University James Comprehensive Cancer Center, 460 W. 12th Ave, Columbus, OH, 43210, USA. [email protected].
  13. Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA. [email protected].

PMID: 35012610 DOI: 10.1186/s13045-021-01222-y

Abstract

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

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.

© 2022. The Author(s).

Keywords: CD24Fc; COVID-19; Cytokine score; Immunophenotyping; Soluble CD24

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