Single-cell RNA Sequencing and Multiple Bioinformatics Methods to Identify the Immunity and Ferroptosis-related Biomarkers of SARS-CoV-2 Infections to Ischemic Stroke

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2023 Aug 22

PMID 37606960

Authors

Xiang Zhao

Qingyu Liang

Hao Li

Zhitao Jing

Dongmei Pei

Affiliations

Soon will be listed here.

Abstract

Background: Since December 2019, Coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. There is an increased risk of ischemic stroke (IS) associated with COVID-19. However, few studies have been reported to explain the potential correlation between COVID-19 and IS.

Methods: We investigated the relationship and relevant mechanisms between COVID-19 and IS using single-cell RNA sequencing and multiple bioinformatics approaches.

Results: By intersecting differentially expressed genes and WGCNA critical module genes, we obtained 73 COVID-19-related IS genes. According to the KEGG pathway analysis, the COVID-19-related IS disease genes were significantly enriched in the hematopoietic cell lineage pathway, ribosome pathway, COVID-19 pathway and primary immunodeficiency pathway. Finally, three genes associated with immunity (B4GALT5, CRISPLD2, F5) and two genes associated with ferroptosis (ACSL1, CREB5) were identified up-regulated in COVID-19-related IS. Significantly, it was found that all five genes were highly expressed in monocytes by single cell RNA sequencing.

Conclusion: We believe these genes (B4GALT5, CRISPLD2, F5, ACSL1, CREB5) may regulate the immune response and ferroptosis of multiple immune cells, mainly including monocytes, which may contribute to the development of COVID-19-related IS. In addition, these genes may be potential targets for the treatment of COVID-19-related IS.

Citing Articles

Deciphering infected cell types, hub gene networks and cell-cell communication in infectious bronchitis virus via single-cell RNA sequencing.

Liukang C, Zhao J, Tian J, Huang M, Liang R, Zhao Y PLoS Pathog. 2024; 20(5):e1012232.

PMID: 38743760 PMC: 11125504. DOI: 10.1371/journal.ppat.1012232.

References

Lindqvist I, Cunningham J, Mulder J, Feresiadou A, Rostami E, Virhammar J . Myoclonus in patients with COVID-19: Findings of autoantibodies against brain structures in cerebrospinal fluid. Eur J Neurol. 2023; 30(10):3142-3148. DOI: 10.1111/ene.15958. View

Libruder C, Hershkovitz Y, Ben-Yaish S, Tanne D, Keinan-Boker L, Binyaminy B . An Increased Risk for Ischemic Stroke in the Short-Term Period following COVID-19 Infection: A Nationwide Population-Based Study. Neuroepidemiology. 2023; 57(4):253-259. PMC: 11251667. DOI: 10.1159/000531163. View

Liu Y, Liao X, Qin Y, Mo X, Luo S . Identification of as a Prognostic Biomarker in Patients with Gastric Cancer. Biomed Res Int. 2020; 2020:9280841. PMC: 7064826. DOI: 10.1155/2020/9280841. View

Bulla R, Rossi L, Furlanis G, Agostinis C, Toffoli M, Balduit A . A likely association between low mannan-binding lectin level and brain fog onset in long COVID patients. Front Immunol. 2023; 14:1191083. PMC: 10312368. DOI: 10.3389/fimmu.2023.1191083. View

Newman A, Liu C, Green M, Gentles A, Feng W, Xu Y . Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015; 12(5):453-7. PMC: 4739640. DOI: 10.1038/nmeth.3337. View

Ren X, Wen W, Fan X, Hou W, Su B, Cai P . COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas. Cell. 2021; 184(7):1895-1913.e19. PMC: 7857060. DOI: 10.1016/j.cell.2021.01.053. View

Zhou N, Bao J . FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database (Oxford). 2020; 2020. PMC: 7100629. DOI: 10.1093/database/baaa021. View

Merad M, Martin J . Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020; 20(6):355-362. PMC: 7201395. DOI: 10.1038/s41577-020-0331-4. View

Zhang R, Sun C, Chen X, Han Y, Zang W, Jiang C . COVID-19-Related Brain Injury: The Potential Role of Ferroptosis. J Inflamm Res. 2022; 15:2181-2198. PMC: 8994634. DOI: 10.2147/JIR.S353467. View

10.

Jackson R, Griesel B, Short K, Sparling D, Freeman W, Olson A . Weight Loss Results in Increased Expression of Anti-Inflammatory Protein CRISPLD2 in Mouse Adipose Tissue. Obesity (Silver Spring). 2019; 27(12):2025-2036. PMC: 6873817. DOI: 10.1002/oby.22652. View

11.

Mahmud S, Al-Mustanjid M, Akter F, Rahman M, Ahmed K, Rahman M . Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 infections to idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease patients. Brief Bioinform. 2021; 22(5). PMC: 8083324. DOI: 10.1093/bib/bbab115. View

12.

Nomura N, Zu Y, Maekawa T, Tabata S, Akiyama T, Ishii S . Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. J Biol Chem. 1993; 268(6):4259-66. View

13.

Verveen A, Verfaillie S, Visser D, Csorba I, Coomans E, Koch D . Neurobiological basis and risk factors of persistent fatigue and concentration problems after COVID-19: study protocol for a prospective case-control study (VeCosCO). BMJ Open. 2023; 13(6):e072611. PMC: 10314688. DOI: 10.1136/bmjopen-2023-072611. View

14.

Overmyer K, Shishkova E, Miller I, Balnis J, Bernstein M, Peters-Clarke T . Large-Scale Multi-omic Analysis of COVID-19 Severity. Cell Syst. 2020; 12(1):23-40.e7. PMC: 7543711. DOI: 10.1016/j.cels.2020.10.003. View

15.

Sette A, Crotty S . Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021; 184(4):861-880. PMC: 7803150. DOI: 10.1016/j.cell.2021.01.007. View

16.

Pomilio A, Vitale A, Lazarowski A . COVID-19 and Alzheimer's Disease: Neuroinflammation, Oxidative Stress, Ferroptosis, and Mechanisms Involved. Curr Med Chem. 2022; 30(35):3993-4031. DOI: 10.2174/0929867329666221003101548. View

17.

Krug T, Gabriel J, Taipa R, Fonseca B, Domingues-Montanari S, Fernandez-Cadenas I . TTC7B emerges as a novel risk factor for ischemic stroke through the convergence of several genome-wide approaches. J Cereb Blood Flow Metab. 2012; 32(6):1061-72. PMC: 3367223. DOI: 10.1038/jcbfm.2012.24. View

18.

Levy Y, Wiedemann A, Hejblum B, Durand M, Lefebvre C, Surenaud M . CD177, a specific marker of neutrophil activation, is associated with coronavirus disease 2019 severity and death. iScience. 2021; 24(7):102711. PMC: 8189740. DOI: 10.1016/j.isci.2021.102711. View

19.

Chen X, Kang R, Kroemer G, Tang D . Ferroptosis in infection, inflammation, and immunity. J Exp Med. 2021; 218(6). PMC: 8126980. DOI: 10.1084/jem.20210518. View

20.

OConnell G, Treadway M, Petrone A, Tennant C, Lucke-Wold N, Chantler P . Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post-stroke blood brain barrier disruption. Sci Rep. 2017; 7(1):1172. PMC: 5430856. DOI: 10.1038/s41598-017-01178-5. View