In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19

Zhang, Xiao Jing; Qin, Juan Juan; Xu, Cheng; Shen, Lijun; Zhao, Yan; Yuan, Yufeng; Lei, Fang; Chen, Ming Ming; Yang, Huilin; Bai, Lei; Song, Xiaohui; Lin, Lijin; Meng, Xiaomei; Zhou, Feng; Zhou, Jianghua; She, Zhi Gang; Zhu, Lihua; Ma, Xin‐Liang; Xu, Qingbo; Ye, Ping; Chen, Guohua; Li, Liming; Mao, Weiming; Yan, Youqin; Xiao, Bing; Lu, Zhigang; Peng, Gang; Li, Mingyu; Yang, Jun; Yang, Lijing; Zhang, Changjiang; Lu, Haofeng; Xia, Xin; Wang, Daihong; Liao, Xiaofeng; Xiang, Wei; Zhang, Bing Hong; Zhang, Xin; Yang, Juan; Zhao, Guang Nian; Zhang, Peng; Liu, Peter P.; Loomba, Rohit; Ji, Yan; Xia, Jiahong; Wang, Yibin; Cai, Jingjing; Guo, Jiao; Li, Hongliang

doi:10.1016/j.cmet.2020.06.015

Cited by 438 publications

(575 citation statements)

References 55 publications

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“…It is therefore possible that these small regulatory molecules and their interactions with long non-coding RNAs are part of the COVID-19 pathogenesis. If so, they also provide therapeutic targets and opportunities for intervention, possibly in conjunction with other immunomodulatory efforts ( 165 ) and with agents which may upregulate the expression of NEAT1, such as statins ( 33 ). In conclusion, establishing the interlinks between specific ncRNAs and their targets may augment our understanding of the inflammatory course of COVID-19, aid in designing intervention strategies, and lead to potential novel diagnostic and therapeutic means.…”

Section: Discussionmentioning

confidence: 99%

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

2020

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The COVID-19 pandemic exerts inflammation-related parasympathetic complications and post-infection manifestations with major inter-individual variability. To seek the corresponding transcriptomic origins for the impact of COVID-19 infection and its aftermath consequences, we sought the relevance of long and short non-coding RNAs (ncRNAs) for susceptibility to COVID-19 infection. We selected inflammation-prone men and women of diverse ages among the cohort of Genome Tissue expression (GTEx) by mining RNA-seq datasets from their lung, and blood tissues, followed by quantitative qRT-PCR, bioinformatics-based network analyses and thorough statistics compared to brain cell culture and infection tests with COVID-19 and H1N1 viruses. In lung tissues from 57 inflammation-prone, but not other GTEx donors, we discovered sharp declines of the lung pathology-associated ncRNA DANCR and the nuclear paraspeckles forming neuroprotective ncRNA NEAT1. Accompanying increases in the acetylcholine-regulating transcripts capable of controlling inflammation co-appeared in SARS-CoV-2 infected but not H1N1 influenza infected lung cells. The lung cells-characteristic DANCR and NEAT1 association with inflammation-controlling transcripts could not be observed in blood cells, weakened with age and presented sex-dependent links in GTEx lung RNA-seq dataset. Supporting active involvement in the inflammatory risks accompanying COVID-19, DANCR’s decline associated with decrease of the COVID-19-related cellular transcript ACE2 and with sex-related increases in coding transcripts potentiating acetylcholine signaling. Furthermore, transcription factors (TFs) in lung, brain and cultured infected cells created networks with the candidate transcripts, indicating tissue-specific expression patterns. Supporting links of post-infection inflammatory and cognitive damages with cholinergic mal-functioning, man and woman-originated cultured cholinergic neurons presented differentiation-related increases of DANCR and NEAT1 targeting microRNAs. Briefly, changes in ncRNAs and TFs from inflammation-prone human lung tissues, SARS-CoV-2-infected lung cells and man and woman-derived differentiated cholinergic neurons reflected the inflammatory pathobiology related to COVID-19. By shifting ncRNA differences into comparative diagnostic and therapeutic profiles, our RNA-sequencing based Resource can identify ncRNA regulating candidates for COVID-19 and its associated immediate and predicted long-term inflammation and neurological complications, and sex-related therapeutics thereof. Our findings encourage diagnostics of involved tissue, and further investigation of NEAT1-inducing statins and anti-cholinergic medications in the COVID-19 context.

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Section: Discussionmentioning

confidence: 99%

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

2020

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“…To date, most of available data from clinical studies support the protective effect of statins against SARS-CoV-2 infection. Indeed, a number of retrospective studies have shown lower inflammatory parameters, decreased incidence of severe clinical manifestations or reduced mortality rates in COVID-19 patients under statin treatment as compared to those not taking statins [ 41 , 42 ]. However, consistent evidence from prospective studies is not currently available.…”

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confidence: 99%

Commentary: Statins, COVID-19, and coronary artery disease: killing two birds with one stone

et al. 2020

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“…The powerful current state-of-the-art anti-inflammatory corticosteroid therapy (e.g., dexamethasone) needs to be carefully evaluated in patients with diabetes, because of their well-known secondary diabetogenic adverse effects at high doses. Rather, specific and promising anti-inflammatory compounds, such as anti-IL-6, anti-IL-1, and IL-1Ra, which showed robust reduction in markers of inflammation and improvement in glycemia in many clinical trials ( 17 ), or lipid lowering anti-inflammatory statins ( 19 ) should be considered for the symptomatic therapy for COVID-19 patients with diabetes ( Figure 1B ).…”

Section: Discussionmentioning

confidence: 99%

Commentary: A Human Pluripotent Stem Cell-Based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids

Ardestani

Maedler

2020

Front. Endocrinol.

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In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19

Cited by 438 publications

References 55 publications

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

Commentary: Statins, COVID-19, and coronary artery disease: killing two birds with one stone

Commentary: A Human Pluripotent Stem Cell-Based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids

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