Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology.
Aged
Alarmins
/ immunology
CD24 Antigen
/ chemistry
COVID-19
/ immunology
Cytokine Release Syndrome
/ immunology
Double-Blind Method
Female
HMGB1 Protein
/ immunology
Heat-Shock Proteins
/ immunology
Homeostasis
/ drug effects
Humans
Inflammation
/ immunology
Killer Cells, Natural
/ immunology
Male
Middle Aged
SARS-CoV-2
/ drug effects
Solubility
T-Lymphocytes
/ immunology
Treatment Outcome
CD24Fc
COVID-19
Cytokine score
Immunophenotyping
Soluble CD24
Journal
Journal of hematology & oncology
ISSN: 1756-8722
Titre abrégé: J Hematol Oncol
Pays: England
ID NLM: 101468937
Informations de publication
Date de publication:
10 01 2022
10 01 2022
Historique:
received:
15
11
2021
accepted:
18
12
2021
entrez:
11
1
2022
pubmed:
12
1
2022
medline:
27
1
2022
Statut:
epublish
Résumé
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. 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. 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 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.
Sections du résumé
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.
Identifiants
pubmed: 35012610
doi: 10.1186/s13045-021-01222-y
pii: 10.1186/s13045-021-01222-y
pmc: PMC8744064
doi:
Substances chimiques
Alarmins
0
CD24 Antigen
0
HMGB1 Protein
0
Heat-Shock Proteins
0
Banques de données
ClinicalTrials.gov
['NCT04317040']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5Subventions
Organisme : NCI NIH HHS
ID : R37CA233770
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NCI NIH HHS
ID : P30CA016058
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI077283
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA213290
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA233770
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2022. The Author(s).
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