tetano
Editor, Senior Moderator
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
No-Joon Song[SUP] #[/SUP][SUP] 1 [/SUP], Carter Allen[SUP] #[/SUP][SUP] 1 2 [/SUP], Anna E Vilgelm[SUP] #[/SUP][SUP] 1 3 [/SUP], Brian P Riesenberg[SUP] #[/SUP][SUP] 1 [/SUP], Kevin P Weller[SUP] 1 [/SUP], Kelsi Reynolds[SUP] 1 [/SUP], Karthik B Chakravarthy[SUP] 1 4 [/SUP], Amrendra Kumar[SUP] 3 5 [/SUP], Aastha Khatiwada[SUP] 6 [/SUP], Zequn Sun[SUP] 6 [/SUP], Anjun Ma[SUP] 1 2 [/SUP], Yuzhou Chang[SUP] 1 2 [/SUP], Mohamed Yusuf[SUP] 1 [/SUP], Anqi Li[SUP] 1 4 [/SUP], Cong Zeng[SUP] 7 [/SUP], John P Evans[SUP] 7 [/SUP], Donna Bucci[SUP] 1 [/SUP], Manuja Gunasena[SUP] 8 9 [/SUP], Menglin Xu[SUP] 10 [/SUP], Namal P M Liyanage[SUP] 8 9 [/SUP], Chelsea Bolyard[SUP] 1 [/SUP], Maria Velegraki[SUP] 1 [/SUP], Shan-Lu Liu[SUP] 7 [/SUP], Qin Ma[SUP] 1 2 [/SUP], Martin Devenport[SUP] 11 [/SUP], Yang Liu[SUP] 11 [/SUP], Pan Zheng[SUP] 11 [/SUP], Carlos D Malvestutto[SUP] #[/SUP][SUP] 10 [/SUP], Dongjun Chung[SUP] #[/SUP][SUP] 1 2 [/SUP], Zihai Li[SUP] #[/SUP][SUP] 12 13 [/SUP]
Affiliations
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[SUP]+[/SUP] T cells, CD4[SUP]+[/SUP] T cells, and CD56[SUP]+[/SUP] 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.
Keywords: CD24Fc; COVID-19; Cytokine score; Immunophenotyping; Soluble CD24.
. 2022 Jan 10;15(1):5.
doi: 10.1186/s13045-021-01222-y.
Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology
No-Joon Song[SUP] #[/SUP][SUP] 1 [/SUP], Carter Allen[SUP] #[/SUP][SUP] 1 2 [/SUP], Anna E Vilgelm[SUP] #[/SUP][SUP] 1 3 [/SUP], Brian P Riesenberg[SUP] #[/SUP][SUP] 1 [/SUP], Kevin P Weller[SUP] 1 [/SUP], Kelsi Reynolds[SUP] 1 [/SUP], Karthik B Chakravarthy[SUP] 1 4 [/SUP], Amrendra Kumar[SUP] 3 5 [/SUP], Aastha Khatiwada[SUP] 6 [/SUP], Zequn Sun[SUP] 6 [/SUP], Anjun Ma[SUP] 1 2 [/SUP], Yuzhou Chang[SUP] 1 2 [/SUP], Mohamed Yusuf[SUP] 1 [/SUP], Anqi Li[SUP] 1 4 [/SUP], Cong Zeng[SUP] 7 [/SUP], John P Evans[SUP] 7 [/SUP], Donna Bucci[SUP] 1 [/SUP], Manuja Gunasena[SUP] 8 9 [/SUP], Menglin Xu[SUP] 10 [/SUP], Namal P M Liyanage[SUP] 8 9 [/SUP], Chelsea Bolyard[SUP] 1 [/SUP], Maria Velegraki[SUP] 1 [/SUP], Shan-Lu Liu[SUP] 7 [/SUP], Qin Ma[SUP] 1 2 [/SUP], Martin Devenport[SUP] 11 [/SUP], Yang Liu[SUP] 11 [/SUP], Pan Zheng[SUP] 11 [/SUP], Carlos D Malvestutto[SUP] #[/SUP][SUP] 10 [/SUP], Dongjun Chung[SUP] #[/SUP][SUP] 1 2 [/SUP], Zihai Li[SUP] #[/SUP][SUP] 12 13 [/SUP]
Affiliations
- 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[SUP]+[/SUP] T cells, CD4[SUP]+[/SUP] T cells, and CD56[SUP]+[/SUP] 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.
Keywords: CD24Fc; COVID-19; Cytokine score; Immunophenotyping; Soluble CD24.