Comparative Transcriptomic Analyses of Peripheral Blood Mononuclear Cells of COVID-19 Patients without Pneumonia and with Severe Pneumonia in the First Year of Follow-Up.

Autor: Kayalar O; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye., Cetinkaya PD; Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana 01790, Türkiye., Eldem V; Department of Biology, Science Faculty, Istanbul University, Istanbul 34134, Türkiye., Argun Baris S; Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, Kocaeli 41380, Türkiye., Kokturk N; Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye., Kuralay SC; Department of Biology, Science Faculty, Istanbul University, Istanbul 34134, Türkiye., Rajabi H; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye., Konyalilar N; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye., Mortazavi D; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye., Korkunc SK; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye., Erkan S; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye., Aksoy GT; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye., Eyikudamaci G; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye., Pinar Deniz P; Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana 01790, Türkiye., Baydar Toprak O; Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana 01790, Türkiye., Yildiz Gulhan P; Department of Pulmonary Medicine, Faculty of Medicine, Duzce University, Duzce 81620, Türkiye., Sagcan G; Department of Pulmonary Medicine, Altunizade Acibadem Hospital, Istanbul 34662, Türkiye., Kose N; Department of Pulmonary Medicine, Bilecik Training and Research Hospital, Bilecik 11230, Türkiye., Tomruk Erdem A; Department of Pulmonary Medicine, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak 67100, Türkiye., Fakili F; Department of Pulmonary Medicine, Faculty of Medicine, Gaziantep University, Gaziantep 27310, Türkiye., Ozturk O; Department of Pulmonary Medicine, Faculty of Medicine, Suleyman Demirel University, Isparta 32260, Türkiye., Basyigit I; Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, Kocaeli 41380, Türkiye., Boyaci H; Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, Kocaeli 41380, Türkiye., Azak E; Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Kocaeli University, Kocaeli 41380, Türkiye., Ulukavak Ciftci T; Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye., Oguzulgen IK; Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye., Ozger HS; Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye., Aysert Yildiz P; Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye., Hanta I; Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana 01790, Türkiye., Ataoglu O; Department of Pulmonary Medicine, Faculty of Medicine, Duzce University, Duzce 81620, Türkiye., Ercelik M; Department of Pulmonary Medicine, Faculty of Medicine, Duzce University, Duzce 81620, Türkiye., Cuhadaroglu C; Department of Pulmonary Medicine, Altunizade Acibadem Hospital, Istanbul 34662, Türkiye., Okur HK; Department of Pulmonary Medicine, Altunizade Acibadem Hospital, Istanbul 34662, Türkiye., Tor MM; Department of Pulmonary Medicine, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak 67100, Türkiye., Nurlu Temel E; Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Suleyman Demirel University, Isparta 32260, Türkiye., Kul S; Department of Biostatistics, Faculty of Medicine, Gaziantep University, Gaziantep 27310, Türkiye., Tutuncu Y; Department of Immunology, Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University Istanbul, Istanbul 34010, Türkiye., Itil O; Department of Pulmonary Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, Türkiye., Bayram H; Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye.; Department of Pulmonary Medicine, School of Medicine, Koc University, Istanbul 34010, Türkiye.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2024 Jul 28; Vol. 16 (8). Date of Electronic Publication: 2024 Jul 28.
DOI: 10.3390/v16081211
Abstrakt: The multisystemic effects of COVID-19 may continue for a longer time period following the acute phase, depending on the severity of the disease. However, long-term systemic transcriptomic changes associated with COVID-19 disease and the impact of disease severity are not fully understood. We aimed to investigate the impact of COVID-19 and its severity on transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) following 1 year of the disease. PBMCs were isolated from the peripheral blood of healthy control donors who did not have COVID-19 (C; n = 13), from COVID-19 patients without pneumonia (NP; n = 11), and from COVID-19 patients with severe pneumonia (SP; n = 10) after 1-year of follow-up. Following RNA isolation from PBMCs, high-quality RNAs were sequenced after creating a library. Differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified using Benjamini-Hochberg correction and they were analysed for hierarchical clustering and principal component analysis (PCA). Intergroup comparisons (C vs. NP, C vs. SP, and NP vs. SP) of DEGs and DElncRNAs were performed and hub genes were determined. Functional enrichment analyses of DEGs and DElncRNAs were made using Metascape (v3.5.20240101) and the first version of NCPATH. The RNA sequencing analysis revealed 4843 DEGs and 1056 DElncRNAs in "C vs. NP", 1651 DEGs and 577 DElncRNAs in "C vs. SP", and 954 DEGs and 148 DElncRNAs in "NP vs. SP", with 291 DEGs and 70 DElncRNAs shared across all groups, respectively. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation and downregulated DEGs to viral infections and immune responses. The analysis showed that 291 common and 14 hub genes were associated with pneumonia and that these genes could be regulated by the transcription factors JUN and NFκB1 carrying the NFκB binding site. We also revealed unique immune cell signatures across DEG categories indicating that the upregulated DEGs were associated with neutrophils and monocytes, while downregulated DEGs were associated with CD4 memory effector T cells. The comparative transcriptomic analysis of NP and SP groups with 52 gene signatures suggestive of IPF risk showed a lower risk of IPF in the SP group than the NP patients. Our findings suggest that COVID-19 may cause long term pathologies by modulating the expression of various DEGs, DeLncRNAs, and hub genes at the cellular level.
Databáze: MEDLINE
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