Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity

Giroux, Nicholas; Ding, Shengli; McClain, Micah T.; Burke, Thomas W.; Petzold, Elizabeth; Chung, Hong A; Palomino, Grecia Rivera; Wang, Ergang; Rui, Xiaoting; Bose, Shree; Rotstein, Tomer; Nicholson, Bradly P.; Chen, Tianyi; Henao, Ricardo; Sempowski, Gregory D.; Denny, Thomas N.; Ko, Emily R; Ginsburg, Geoffrey S.; Kraft, Bryan; Tsalik, Ephraim L.; Woods, Christopher W.; Shen, Xiling

doi:10.1101/2020.12.04.412155

Cited by 4 publications

(4 citation statements)

References 58 publications

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“…Moderate), and in extremely severe (ICU) versus severe patients (ICU vs. Severe), which were not investigated previously using RNA-Seq of PBMCs representing different COVID-19 stages [8][9][10]12 . This analysis was performed to gain insights into genes or pathways differentially regulated during the progression of this disease from the moderate to extremely severe condition.…”

Section: Resultsmentioning

confidence: 99%

“…Advances in high-throughput sequencing technologies have enabled gaining insights into the perturbations in the expression of different genes and biological pathways that result in a wide range of clinical manifestations in hosts. Although several studies have focused on differential gene expression during the SARS-CoV-2 infection [5][6][7][8][9][10][11] , these analyses are based mainly on the criteria of expression fold-change and statistical significance for identifying. It is recognized that many of the lowly expressed genes may also be biologically or medically significant but may get filtered out due to their not meeting the preset criteria.…”

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confidence: 99%

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Molecular signatures in the progression of COVID-19 severity

Azad

2022

Sci Rep

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SARS-CoV-2 is the causative agent of COVID-19 that has infected over 642 million and killed over 6.6 million people around the globe. Underlying a wide range of clinical manifestations of this disease, from moderate to extremely severe systemic conditions, could be genes or pathways differentially expressing in the hosts. It is therefore important to gain insights into pathways involved in COVID-19 pathogenesis and host defense and thus understand the host response to this pathogen at the physiological and molecular level. To uncover genes and pathways involved in the differential clinical manifestations of this disease, we developed a novel gene co-expression network based pipeline that uses gene expression obtained from different SARS-CoV-2 infected human tissues. We leveraged the network to identify novel genes or pathways that likely differentially express and could be physiologically significant in the COVID-19 pathogenesis and progression but were deemed statistically non-significant and therefore not further investigated in the original studies. Our network-based approach aided in the identification of co-expression modules enriched in differentially expressing genes (DEGs) during different stages of COVID-19 and enabled discovery of novel genes involved in the COVID-19 pathogenesis, by virtue of their transcript abundance and association with genes expressing differentially in modules enriched in DEGs. We further prioritized by considering only those enriched gene modules that have most of their genes differentially expressed, inferred by the original studies or this study, and document here 7 novel genes potentially involved in moderate, 2 in severe, 48 in extremely severe COVID-19, and 96 novel genes involved in the progression of COVID-19 from severe to extremely severe conditions. Our study shines a new light on genes and their networks (modules) that drive the progression of COVID-19 from moderate to extremely severe condition. These findings could aid development of new therapeutics to combat COVID-19.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Molecular signatures in the progression of COVID-19 severity

Azad

2022

Sci Rep

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“…Accordingly, robust epigenetic and metabolic changes, which may be associated with macrophage tolerance and innate immune memory, have recently been reported in COVID-19 patients. Genome-wide CRISPR screens using SARS-CoV-2 showed that genes encoding the SWI/SNF chromatin-remodeling complex are pro-viral factors (Wei et al, 2021), and the distinct chromatin accessibility changes during virus infection were associated with COVID-19 severity (Giroux et al, 2020). Alterations of metabolic pathways, such as kynurenine, which is linked to COVID-19 severity (Nie et al, 2021;Shen et al, 2020) and sepsis (van der Poll et al, 2017), were also demonstrated.…”

Section: Immunoparalysis and Innate Immune Memorymentioning

confidence: 99%

An Impaired Inflammatory and Innate Immune Response in COVID-19

Park

2021

Molecules and Cells

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The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.

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“…Giroux group demonstrated chromatin remodeling in certain innate immune populations (CD14+ monocytes) to be associated with divergence in symptom severity and the identified transcription factors, regulatory elements, and downstream pathways. All these would be potential prognostic markers for COVID-19 infection (Giroux et al 2020).…”

Section: Histone Modificationsmentioning

confidence: 99%

Deciphering epigenetic(s) role in modulating susceptibility to and severity of COVID-19 infection and/or outcome: a systematic rapid review

AbdelHamid

Refaat

Benjamin

et al. 2021

Environ Sci Pollut Res

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COVID-19 pandemic waves hitting worldwide result in drastic postinfection complications with interindividual variations, which raised the question for the cause of these observed variations. This urged to think "the impact of environment-affected genes"? In an attempt to unravel the impact of environment-affected genes, a systematic rapid review was conducted to study "the impact of host or viral epigenetic modulation on COVID-19 infection susceptibility and/or outcome." Electronic databases including Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, PubMed, and Google Scholar, and other databases were searched. The search strings included "COVID-19" OR "SARS-CoV-2" AND (Epigenetics'). Articles with randomized clinical trials (RCTs) and observational study designs, conducted on humans and available in the English language, were selected, with respect to "The interplay between the SARS-CoV-2 virus and Epigenetics" published from 2020 to February 2021 (but not limited to 2020, being expanded to 2015). Database search yielded 1330 articles; after screening, exclusion, and further filtrations, 51 articles were included. Susceptibility to COVID-19 infection is related to the viral-microRNAs (miRNAs) which alter virulence of the transmitted SARS-CoV-2 strains and impact host-miRNA-related innate immunity. Host-DNA methylation and/or chromatin remodeling may be implicated in severe cytokine storm that can ultimately results in fatal outcome.

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Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity

Cited by 4 publications

References 58 publications

Molecular signatures in the progression of COVID-19 severity

Molecular signatures in the progression of COVID-19 severity

An Impaired Inflammatory and Innate Immune Response in COVID-19

Deciphering epigenetic(s) role in modulating susceptibility to and severity of COVID-19 infection and/or outcome: a systematic rapid review

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