Corticosteroids reduce pathologic interferon responses by downregulating STAT1 in patients with high-risk COVID-19

Jeong, Hyun‐Woo; Lee, Jeong Seok; Ko, Jae-Hoon; Hong, Seunghee; Oh, Sang Taek; Choi, Seongkyun; Peck, Kyong Ran; Yang, Ji; Chung, Seok; Kim, Sung-Han; Kim, So Hyun; Shin, Eui‐Cheol

doi:10.1038/s12276-023-00964-8

Cited by 5 publications

(5 citation statements)

References 50 publications

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“… 25 The type I IFN canonical and noncanonical signaling partially relies on a high level of signal transducer and activator of transcription 1 (STAT1) or phosphorylated STAT1 (pSTAT1). 26 These findings are consistent with our transcriptomics data. Levels of other cytokines, such as IL-6, are generally elevated in critically ill patients with COVID-19.…”

Section: Discussionsupporting

confidence: 92%

“…In patients with COVID-19, corticosteroids inhibit the pathologic interferon response of monocytes by down-regulating STAT1, and tofacitinib prevents IL-mediated hyperinflammation by blocking the JAK/STAT pathway. 26 , 30 Our findings and those of other studies suggest that currently available medications for IBD do not aggravate or increase the rate of SARS-CoV-2 infection, and patients with IBD can continue to receive IBD-related medications during the pandemic. 31 …”

Section: Discussionsupporting

confidence: 66%

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Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China

Li,

Zhang,

Lin

et al. 2024

JIR

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Purpose The rapid global spread of the SARS-CoV-2 Omicron variant introduces a novel complication: the emergence of IBD (inflammatory bowel disease)-like ulcers in certain patients. This research delves into this new challenge by juxtaposing the clinical manifestations and genetic expression patterns of individuals affected by the Omicron variant of COVID-19 with those diagnosed with IBD. It aims to decode the link between these conditions, potentially shedding light on previously unexplored facets of COVID-19 pathophysiology. This investigation emphasizes gene expression analysis as a key tool to identify wider disease correlations and innovative therapeutic avenues. Patients and Methods From March to December 2022, patients with SARS-CoV-2 Omicron infection and inflammatory bowel disease and healthy controls were recruited in Shanghai East Hospital, Shanghai, China. The epidemiological and clinical characteristics of the patients were compared. Four RNA sequencing datasets (GSE205244, GSE201530, GSE174159, and GSE186507) were extracted from the Gene Expression Omnibus database to detect mutually differentially expressed genes and common pathways in patients with SARS-CoV-2 infection and inflammatory bowel disease. Results Compared to patients with active inflammatory bowel disease, patients with SARS-CoV-2 infection were more likely to have elevated interferon-α levels and an increased lymphocyte count and less likely to have high interleukin-6, tumor necrosis factor-α, and C-reactive protein levels and an elevated neutrophil count. A total of 51 common differentially expressed genes were identified in the four RNA-sequencing datasets. Enrichment analysis suggested that these genes were related to inflammation and the immune response, especially the innate immune response and nucleotide oligomerization domain-like receptor signaling pathway. Conclusion The inflammation and immune-response pathways in COVID-19 and inflammatory bowel disease have several similarities and some differences. The study identifies the NLR signaling pathway’s key role in both COVID-19 and IBD, suggesting its potential as a target for therapeutic intervention and vaccine development.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 66%

Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China

Li,

Zhang,

Lin

et al. 2024

JIR

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“…Blood samples were labeled with patient symbol and an additional one letter suffix; for instance, PTF1 treated for 2 days with GC is labelled as PTF1a. The authors reported that the highest levels of GC-dependent differential expression was observed in monocytes compared to other immune cells 36 . Therefore, the ARE-mRNA analysis was performed in monocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Single cell RNA-seq data of COVID-19 patients treated with GCs were from (GSE188172) 36 . The mapped mRNA counts from patients’ sampled pre and post GC treatment (PTF1, PTF2, PTF4, PTF5, PTM1 and PTM4) were downloaded from NCBI GEO database GSE188172.…”

Section: Methodsmentioning

confidence: 99%

Global analysis of the abundance of AU-rich mRNAs in response to glucocorticoid treatment

Muazzen,

Moghrabi,

Bakheet

et al. 2024

Sci Rep

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Glucocorticoids (GC) like dexamethasone (Dex) are potent anti-inflammatory agents with diverse cellular functions including the potentiation of the activity of AU-rich elements (AREs). AREs are cis-acting instability sequence elements located in the 3′UTRs of many inflammatory mediator mRNAs. Here, available RNA-seq data were used to investigate the effect of GCs on the ARE-mRNA-transcriptome. At a global scale, ARE-mRNAs had a tendency to be downregulated after GC-treatment of the A549 lung cancer cell-line, but with notable cases of upregulation. mRNA stability experiments indicated that not only the downregulated, but also the upregulated ARE-mRNAs are destabilized by Dex-treatment. Several of the most upregulated ARE-mRNAs code for anti-inflammatory mediators including the established GC targets DUSP1 and ZFP36; both code for proteins that target ARE-containing mRNAs for destruction. GCs are widely used in the treatment of COVID-19 patients; we show that ARE-mRNAs are more likely to regulate in opposite directions between Dex-treatment and SARS-CoV-2 infections compared to non-ARE mRNAs. The effect of GC treatment on ARE-mRNA abundance was also investigated in blood monocytes of COVID-19 patients. The results were heterogeneous; however, in agreement with in vitro observations, ZFP36 and DUSP1 were often amongst the most differentially expressed mRNAs. The results of this study propose a universal destabilization of ARE-mRNAs by GCs, but a diverse overall outcome in vitro likely due to induced transcription or due to the heterogeneity of COVID-19 patient’s responses in vivo.

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“…This study suggested that during the COVID-19 pandemic, ADA, SEC, and IXE may suppress serum OAS2 and OAS3 levels in patients with psoriasis, thereby preventing psoriasis exacerbation. Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from COVID-19 cohorts also showed that OASs were downregulated in monocytes after corticosteroid treatment [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Biologics protect psoriasis patients from being exacerbated by COVID-19 infection

Zheng,

Chen,

Wang

et al. 2024

Heliyon

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Corticosteroids reduce pathologic interferon responses by downregulating STAT1 in patients with high-risk COVID-19

Cited by 5 publications

References 50 publications

Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China

Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China

Global analysis of the abundance of AU-rich mRNAs in response to glucocorticoid treatment

Biologics protect psoriasis patients from being exacerbated by COVID-19 infection

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