Evidence map›Paper›PMID 33602138›Full record

ArticleBMC genomics2021

SARS-CoV-2 early infection signature identified potential key infection mechanisms and drug targets.

Yue Li, Ashley Duche, Michael R Sayer, Don Roosan, Farid G Khalafalla, Rennolds S Ostrom, Jennifer Totonchy, Moom R Roosan

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
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  11. Artificial Intelligent Context-Aware Machine-Learning Tool to Detect Adverse Drug Events from Social Media Platforms.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2022
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  19. High Expression ofFrontiers in oncology · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Yue LiSchool of Pharmacy, Chapman University, Irvine, CA, 92618, USA.
Ashley DucheSchool of Pharmacy, Chapman University, Irvine, CA, 92618, USA.
Michael R SayerSchool of Pharmacy, Chapman University, Irvine, CA, 92618, USA.
Don RoosanCollege of Pharmacy, Western University of Health Sciences, Pomona, CA, 91766, USA.
Farid G KhalafallaCollege of Pharmacy, California Health Sciences University, Clovis, CA, 93612, USA.
Rennolds S OstromSchool of Pharmacy, Chapman University, Irvine, CA, 92618, USA.
Jennifer TotonchySchool of Pharmacy, Chapman University, Irvine, CA, 92618, USA.
Moom R RoosanSchool of Pharmacy, Chapman University, Irvine, CA, 92618, USA. roosan@chapman.edu.
Chapman University · USWestern University of Health Sciences · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe ongoing COVID-19 outbreak has caused devastating mortality and posed a significant threat to public health worldwide. Despite the severity of this illness and 2.3 million worldwide deaths, the disease mechanism is mostly unknown. Previous studies that characterized differential gene expression due to SARS-CoV-2 infection lacked robust validation. Although vaccines are  now available, effective treatment options are still out of reach.

resultsTo characterize the transcriptional activity of SARS-CoV-2 infection, a gene signature consisting of 25 genes was generated using a publicly available RNA-Sequencing (RNA-Seq) dataset of cultured cells infected with SARS-CoV-2. The signature estimated infection level accurately in bronchoalveolar lavage fluid (BALF) cells and peripheral blood mononuclear cells (PBMCs) from healthy and infected patients (mean 0.001 vs. 0.958; P < 0.0001). These signature genes were investigated in their ability to distinguish the severity of SARS-CoV-2 infection in a single-cell RNA-Sequencing dataset. TNFAIP3, PPP1R15A, NFKBIA, and IFIT2 had shown bimodal gene expression in various immune cells from severely infected patients compared to healthy or moderate infection cases. Finally, this signature was assessed using the publicly available ConnectivityMap database to identify potential disease mechanisms and drug repurposing candidates. Pharmacological classes of tricyclic antidepressants, SRC-inhibitors, HDAC inhibitors, MEK inhibitors, and drugs such as atorvastatin, ibuprofen, and ketoconazole showed strong negative associations (connectivity score < - 90), highlighting the need for further evaluation of these candidates for their efficacy in treating SARS-CoV-2 infection.

conclusionsThus, using the 25-gene SARS-CoV-2 infection signature, the SARS-CoV-2 infection status was captured in BALF cells, PBMCs and postmortem lung biopsies. In addition, candidate SARS-CoV-2 therapies with known safety profiles were identified. The signature genes could potentially also be used to characterize the COVID-19 disease severity in patients' expression profiles of BALF cells.

Indexed as

Drug Delivery SystemsGene Expression ProfilingA549 CellsCOVID-19Gene Expression RegulationHumansModels, BiologicalReproducibility of ResultsSARS-CoV-2Single-Cell AnalysisBronchoalveolar lavage fluid cellsCOVID-19COVID-19 treatmentsPeripheral blood mononuclear cellsSARS-CoV-2 gene expression signature

Identifiers

PMID33602138
PMCPMC7889713
OpenAlexW3130823823

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.