Corticosteroids reduce pathologic interferon responses by downregulating STAT1 in patients with high-risk COVID-19.
Exp Mol Med
; 55(3): 653-664, 2023 03.
Article
in English
| MEDLINE | ID: covidwho-2264624
ABSTRACT
We do not yet understand exactly how corticosteroids attenuate hyperinflammatory responses and alleviate high-risk coronavirus disease 2019 (COVID-19). We aimed to reveal the molecular mechanisms of hyperinflammation in COVID-19 and the anti-inflammatory effects of corticosteroids in patients with high-risk COVID-19. We performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from three independent COVID-19 cohorts cohort 1 was used for comparative analysis of high-risk and low-risk COVID-19 (47 PBMC samples from 28 patients), cohort 2 for longitudinal analysis during COVID-19 (57 PBMC samples from 15 patients), and cohort 3 for investigating the effects of corticosteroid treatment in patients with high-risk COVID-19 (55 PBMC samples from 13 patients). PBMC samples from healthy donors (12 PBMC samples from 12 donors) were also included. Cohort 1 revealed a significant increase in the proportion of monocytes expressing the long noncoding RNAs NEAT1 and MALAT1 in high-risk patients. Cohort 2 showed that genes encoding inflammatory chemokines and their receptors were upregulated during aggravation, whereas genes related to angiogenesis were upregulated during improvement. Cohort 3 demonstrated downregulation of interferon-stimulated genes (ISGs), including STAT1, in monocytes after corticosteroid treatment. In particular, unphosphorylated STAT-dependent ISGs enriched in monocytes from lupus patients were selectively downregulated by corticosteroid treatment in patients with high-risk COVID-19. Corticosteroid treatment suppresses pathologic interferon responses in monocytes by downregulating STAT1 in patients with high-risk COVID-19. Our study provides insights into the mechanisms underlying COVID-19 aggravation and improvement and the effects of corticosteroid treatment.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Leukocytes, Mononuclear
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Exp Mol Med
Journal subject:
Molecular Biology
/
Biochemistry
Year:
2023
Document Type:
Article
Affiliation country:
S12276-023-00964-8
Similar
MEDLINE
...
LILACS
LIS