Discovery of potential imaging and therapeutic targets for severe inflammation in COVID-19 patients
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Abstract
The Coronavirus disease 2019 (COVID-19) has been spreading worldwide with rapidly increased number of deaths. Hyperinflammation mediated by dysregulated monocyte/macrophage function is considered to be the key factor that triggers severe illness in COVID-19. However, no specific targeting molecule has been identified for detecting or treating hyperinflammation related to dysregulated macrophages in severe COVID-19. In this study, previously published single-cell RNA-sequencing data of bronchoalveolar lavage fluid cells from thirteen COVID-19 patients were analyzed with publicly available databases for surface and imageable targets. Immune cell composition according to the severity was estimated with the clustering of gene expression data. Expression levels of imaging target molecules for inflammation were evaluated in macrophage clusters from single-cell RNA-sequencing data. In addition, candidate targetable molecules enriched in severe COVID-19 associated with hyperinflammation were filtered. We found that expression of SLC2A3, which can be imaged by [ 18 F]fluorodeoxyglucose, was higher in macrophages from severe COVID-19 patients. Furthermore, by integrating the surface target and drug-target binding databases with RNA-sequencing data of severe COVID-19, we identified candidate surface and druggable targets including CCR1 and FPR1 for drug delivery as well as molecular imaging. Our results provide a resource in the development of specific imaging and therapy for COVID-19-related hyperinflammation.
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SciScore for 10.1101/2020.07.20.213082: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Preprocessing scRNA-seq data: scRNA-seq data for BAL fluid were downloaded from the Gene Expression Omnibus database (GSE145926). Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Differentially expressed genes and gene set enrichment analyses: To identify marker genes, differential expression analysis was performed using the function FindAllMarkers of the Seurat package with the Wilcoxon rank sum test. Seuratsuggested: (SEURAT, RRID:SCR_007322)We used Reactome to select genes of glycolysis and OXPHOS pathways to examine the overall activity of glycolysis and … SciScore for 10.1101/2020.07.20.213082: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources Preprocessing scRNA-seq data: scRNA-seq data for BAL fluid were downloaded from the Gene Expression Omnibus database (GSE145926). Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Differentially expressed genes and gene set enrichment analyses: To identify marker genes, differential expression analysis was performed using the function FindAllMarkers of the Seurat package with the Wilcoxon rank sum test. Seuratsuggested: (SEURAT, RRID:SCR_007322)We used Reactome to select genes of glycolysis and OXPHOS pathways to examine the overall activity of glycolysis and OXPHOS pathways (40). Reactomesuggested: (Reactome, RRID:SCR_003485)We also used BindingDB, which provides available druggable molecules with target proteins. BindingDBsuggested: (BindingDB, RRID:SCR_000390)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There is a limitation in the present study. Because we analyzed cells from BAL fluid, the results may not be entirely consistent with the immune cell composition or protein expression of the lung tissue itself. Nonetheless, the characteristics or composition of cells in BAL fluid reflect immune cells of the lung associated with inflammation. Thus, targeted imaging of the identified molecules can be applied to in vivo settings. Further study is warranted to validate the feasibility of targeted theranostics of these molecules. Taken together, we demonstrate different compositions of immune cells in BAL fluid from healthy controls and COVID-19 patients. The subpopulations of macrophages differed among the three groups. Regarding alleged imaging markers, SLC2A3 was abundant in macrophage subtypes enriched in severe COVID-19 patients, and we identified SLC3A2, SLC2A3, and FOLR2 as candidate molecules as imaging targets. In addition, various molecular targets, including CCR1, FPR1, and GPR183, are suggested as candidates for drug delivery systems as well as imaging. This work provides a resource to develop targeted imaging and therapeutic strategies for severe pulmonary hyperinflammation related to COVID-19.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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