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Transcriptomic Signatures of Airway Epithelium Infected With SARS-CoV-2: A Balance Between Anti-infection and Virus Load.

ABSTRACT: COVID-19 pneumonia requires effective medical therapies. However, it is a challenge to find therapeutic drugs that not only inhibit viral replication, but also inhibit the accompanying cytokine storm and maintain an appropriate immune response. In this study, the effects of SARS-CoV-2 on gene expression in lung epithelial cells from patients with COVID-19 were systematically evaluated with bioinformatics analysis methods. Transcriptome expression specific to bystander (exposed but uninfected) and infected cells were found, and the vital pathways were identified by conducting differentially expressed gene analysis regarding the relationship between gene signatures of COVID-19 infection and disease severity. We found that a high viral load did not necessarily imply a low response of epithelial cells or a poor disease convalescence. The ability to distinguish the role of virus-correlated genes facilitates the development of potential new medicines and therapies for COVID-19 infection.

SUBMITTER: Meng L

PROVIDER: S-EPMC8419361 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Transcriptomic Signatures of Airway Epithelium Infected With SARS-CoV-2: A Balance Between Anti-infection and Virus Load.

Meng Lingzhang L Qin Houji H Zhao Jingjie J He Siyuan S Wei Qiuju Q Wang Zechen Z Shen Jiajia J Sooranna Suren S Song Jian J

Frontiers in cell and developmental biology 20210823

COVID-19 pneumonia requires effective medical therapies. However, it is a challenge to find therapeutic drugs that not only inhibit viral replication, but also inhibit the accompanying cytokine storm and maintain an appropriate immune response. In this study, the effects of SARS-CoV-2 on gene expression in lung epithelial cells from patients with COVID-19 were systematically evaluated with bioinformatics analysis methods. Transcriptome expression specific to bystander (exposed but uninfected) an ...[more]

PMID: 34497809

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Project description:SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive inflammation and tissue destruction. Primary normal human bronchial epithelial cells are among the first targets of SARS-CoV-2 infection. Here, we show that ColdZyme medical device mouth spray efficiently protected against virus entry, excessive inflammation, and tissue damage. Applying ColdZyme to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI) completely blocked binding of SARS-CoV-2 and increased local complement activation mediated by the virus as well as productive infection of the tissue model. While SARS-CoV-2 infection resulted in exaggerated intracellular complement activation immediately following infection and a drop in transepithelial resistance, these parameters were bypassed by single pretreatment of the tissues with ColdZyme mouth spray. Crucially, our study highlights the importance of testing already evaluated and safe drugs such as ColdZyme mouth spray for maintaining epithelial integrity and hindering SARS-CoV-2 entry within standardized three-dimensional (3D) in vitro models mimicking the in vivo human airway epithelium.IMPORTANCE Although our understanding of COVID-19 continuously progresses, essential questions regarding prophylaxis and treatment remain open. A hallmark of severe SARS-CoV-2 infection is a hitherto-undescribed mechanism leading to excessive inflammation and tissue destruction associated with enhanced pathogenicity and mortality. To tackle the problem at the source, transfer of SARS-CoV-2, subsequent binding, infection, and inflammatory responses have to be avoided. In this study, we used fully differentiated, mucus-producing, and ciliated human airway epithelial cultures to test the efficacy of ColdZyme medical device mouth spray in terms of protection from SARS-CoV-2 infection. Importantly, we found that pretreatment of the in vitro airway cultures using ColdZyme mouth spray resulted in significantly shielding the epithelial integrity, hindering virus binding and infection, and blocking excessive intrinsic complement activation within the airway cultures. Our in vitro data suggest that ColdZyme mouth spray may have an impact in prevention of COVID-19.

Dataset Information

Transcriptomic Signatures of Airway Epithelium Infected With SARS-CoV-2: A Balance Between Anti-infection and Virus Load.

Publications

Transcriptomic Signatures of Airway Epithelium Infected With SARS-CoV-2: A Balance Between Anti-infection and Virus Load.

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