Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.
Nat Med
; 28(1): 201-211, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1517637
ABSTRACT
Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated genes and activated IL-1R2+ neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respiratory Distress Syndrome
/
Dexamethasone
/
Cytokines
/
Pneumonia, Bacterial
/
COVID-19
/
Glucocorticoids
/
Neutrophils
Type of study:
Prognostic study
Topics:
Long Covid
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
Nat Med
Journal subject:
Molecular Biology
/
Medicine
Year:
2022
Document Type:
Article
Affiliation country:
S41591-021-01576-3
Similar
MEDLINE
...
LILACS
LIS