An Integrative Analysis Identifying Transcriptional Features and key Genes Involved in COVID-19

Li, Guoping; Wang, Junyi; He, Xiang; Zhang, Lei; Qin, Ran; Xiong, Anying; Wu, Dehong; Hu, Lingjuan; Song, Qibin; Zhu, Dong Mei

doi:10.2217/epi-2020-0168

Cited by 11 publications

(12 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A subset of upregulated proteins is secretory including S100A12, S100A8, S100A9, SERPINB3, DEFA3, LCN2 and TXN. LCN2, which came up in our study was previously shown to be an important biomarker for viral infection (72,73), and was also reported to be upregulated in transcriptomic and proteomic studies in COVID-19 patients (74,75). It has been shown that virus replication and inflammation goes down when thioredoxin reductase, a reducing agent of TXN is inhibited using auranofin, pointing towards the importance of redox environment during SARS-CoV2 pathogenesis (76), akin to many inflammatory responses which are governed by the redox status of the cell (77).…”

Section: Discussionsupporting

confidence: 62%

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

Biji

Khatun

Swaraj

et al. 2021

Preprint

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) pandemic has lasted more than a year since its first case in December 2019 and yet its social and economic burden continues to grow. While a tremendous amount of OMICs data has been generated from COVID-19 patient samples, the host antiviral response and markers of disease progression remain to be completely delineated. In this study, we have conducted a meta-analysis of published transcriptome and proteome profiles of the nasal swab and bronchioalveolar lavage fluid (BALF) samples of COVID-19 patients to identify high confidence upregulated host factors. This was followed by rank ordering, shortlisting, and validation of overexpression of a set of host factors in a nasal swab/BALF samples from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. This led to the identification of host antiviral response in the upper respiratory tract and potential prognostic markers. Notably, SEPRIN B3 and Thioredoxin were identified as potential antiviral factors. In addition, several S100 family proteins were found to be upregulated in COVID-19 specific and disease severity dependent manner. Overall, this study provides novel insights into the host antiviral mechanisms and COVID-19 disease progression.

show abstract

Section: Discussionsupporting

confidence: 62%

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

Biji

Khatun

Swaraj

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Overall, taking our data and published information together, the S100 family of genes can be considered as reliable prognostic markers of COVID-19 infection and disease progression. Another host factor LCN2, which came up in our study was previously shown to be an important biomarker for viral infection [64] , and was also reported to be upregulated in transcriptomic and proteomic studies in COVID-19 patients [ 65 , 66 ]. Furthermore, Serine protease inhibitor (SERPIN) family genes SERPINB3 and SERPINB1 were present among the initially selected 46 upregulated genes.…”

Section: Discussionmentioning

confidence: 78%

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

Biji

Khatun²,

Swaraj³

et al. 2021

EBioMedicine

View full text Add to dashboard Cite

Background While our battle with the COVID-19 pandemic continues, a multitude of Omics data have been generated from patient samples in various studies. Translation of these data into clinical interventions against COVID-19 remains to be accomplished. Exploring host response to COVID-19 in the upper respiratory tract can unveil prognostic markers and therapeutic targets. Methods We conducted a meta-analysis of published transcriptome and proteome profiles of respiratory samples of COVID-19 patients to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swabs from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Guided by this analysis, we sought to check for potential drug targets. An FDA-approved drug, Auranofin, was tested against SARS-CoV-2 replication in cell culture and Syrian hamster challenge model. Findings The meta-analysis and validation in the COVID-19 cohort revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of severe COVID-19. Furthermore, Thioredoxin (TXN) was found to be consistently upregulated. Auranofin, which targets Thioredoxin reductase, was found to mitigate SARS-CoV-2 replication in vitro. Furthermore, oral administration of Auranofin in Syrian hamsters in therapeutic as well as prophylactic regimen reduced viral replication, IL-6 production, and inflammation in the lungs. Interpretation Elevated mRNA level of S100s in the nasal swabs indicate severe COVID-19 disease, and FDA-approved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model. Funding This study was supported by the DBT-IISc partnership program (DBT (IED/4/2020-MED/DBT)), the Infosys Young Investigator award (YI/2019/1106), DBT-BIRAC grant (BT/CS0007/CS/02/20) and the DBT-Wellcome Trust India Alliance Intermediate Fellowship (IA/I/18/1/503613) to ST lab.

show abstract

“…Median (IQR) age was 53 (43-62) years and sex distribution was equitable: 56% males and 44% females. Median (IQR) time from onset of COVID-19 infection to post-COVID follow up was 9 (6)(7)(8)(9)(10)(11) weeks, but was not significantly different among the three COVID-19 groups. Eight of the subjects admitted to the ICU required intubation and mechanical ventilation, but none required tracheostomy.…”

Section: Resultsmentioning

confidence: 91%

Immunofibrotic drivers of impaired lung function in postacute sequelae of SARS-CoV-2 infection

Chun¹,

Coutavas²,

Pine³

et al. 2021

JCI Insight

View full text Add to dashboard Cite

Introduction: Subjects recovering from COVID-19 frequently experience persistent respiratory ailments which are key elements of post-acute sequelae of SARS-CoV-2 infection (PASC); however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity. Methods: We performed a prospective cohort study of subjects with persistent symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, and plasma samples used for multiplex profiling of inflammatory, metabolic, angiogenic, and fibrotic factors.Results: Sixty-one subjects were enrolled across two academic medical centers at a median of 9 weeks (interquartile range 6-10) after COVID-19 illness: n=13 subjects (21%) mild/nonhospitalized, n=30 (49%) hospitalized/non-critical, and n=18 subjects (30%) hospitalized/intensive care ("ICU"). Fifty-three subjects (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P<0.05), but did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered subjects by past COVID-19 severity. Lipocalin 2 (LCN2), matrix metalloproteinase-7 (MMP-7), and hepatocyte growth factor (HGF) identified by the model were significantly higher in the ICU group (P<0.05) and inversely correlated with FVC and DLCO (P<0.05), and were confirmed in a separate validation cohort (n=53). Conclusions: Subjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets.

show abstract

An Integrative Analysis Identifying Transcriptional Features and key Genes Involved in COVID-19

Cited by 11 publications

References 29 publications

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

Immunofibrotic drivers of impaired lung function in postacute sequelae of SARS-CoV-2 infection

Contact Info

Product

Resources

About