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

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Title
Corticosteroids reduce pathologic interferon responses by downregulating STAT1 in patients with high-risk COVID-19
Author(s)
Jeong, Hyun-Woo; Lee, Jeong Seok; Ko, Jae-Hoon; Hong, Seunghee; Oh, Sang Taek; Choi, Seongkyun; Peck, Kyong Ran; Yang, Ji Hun; Chung, Seok; Kim, Sung-Han; Kim, Yeon-Sook; Eui-Cheol Shin
Publication Date
2023-03
Journal
Experimental & Molecular Medicine, v.55, no.3, pp.653 - 664
Publisher
생화학분자생물학회
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. © 2023, The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/14006
DOI
10.1038/s12276-023-00964-8
ISSN
1226-3613
Appears in Collections:
Korea Virus Research Institute(한국바이러스기초연구소) > Center for Viral Immunology(바이러스 면역 연구센터) > 1. Journal Papers (저널논문)
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