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
Ozgecan Kayalar,
Pelin Duru Cetinkaya,
Vahap Eldem,
Serap Argun Baris,
Nurdan Kokturk,
Selim Can Kuralay,
Hadi Rajabi,
Nur Konyalilar,
Deniz Mortazavi,
Seval Kubra Korkunc,
Sinem Erkan,
Gizem Tuşe Aksoy,
Gul Eyikudamaci,
Pelin Pinar Deniz,
Oya Baydar Toprak,
Pinar Yildiz Gulhan,
Gulseren Sagcan,
Neslihan Kose,
Aysegul Tomruk Erdem,
Fusun Fakili,
Onder Ozturk,
Ilknur Basyigit,
Hasim Boyaci,
Emel Azak,
Tansu Ulukavak Ciftci,
Ipek Kivilcim Oguzulgen,
Hasan Selcuk Ozger,
Pinar Aysert Yildiz,
Ismail Hanta,
Ozlem Ataoglu,
Merve Ercelik,
Caglar Cuhadaroglu,
Hacer Kuzu Okur,
Muge Meltem Tor,
Esra Nurlu Temel,
Seval Kul,
Yıldız Tutuncu,
Oya Itil,
Hasan Bayram
Affiliations
Ozgecan Kayalar
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
Pelin Duru Cetinkaya
Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana 01790, Türkiye
Vahap Eldem
Department of Biology, Science Faculty, Istanbul University, Istanbul 34134, Türkiye
Serap Argun Baris
Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, Kocaeli 41380, Türkiye
Nurdan Kokturk
Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye
Selim Can Kuralay
Department of Biology, Science Faculty, Istanbul University, Istanbul 34134, Türkiye
Hadi Rajabi
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
Nur Konyalilar
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
Deniz Mortazavi
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
Seval Kubra Korkunc
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
Sinem Erkan
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
Gizem Tuşe Aksoy
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
Gul Eyikudamaci
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
Pelin Pinar Deniz
Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana 01790, Türkiye
Oya Baydar Toprak
Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana 01790, Türkiye
Pinar Yildiz Gulhan
Department of Pulmonary Medicine, Faculty of Medicine, Duzce University, Duzce 81620, Türkiye
Gulseren Sagcan
Department of Pulmonary Medicine, Altunizade Acibadem Hospital, Istanbul 34662, Türkiye
Neslihan Kose
Department of Pulmonary Medicine, Bilecik Training and Research Hospital, Bilecik 11230, Türkiye
Aysegul Tomruk Erdem
Department of Pulmonary Medicine, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak 67100, Türkiye
Fusun Fakili
Department of Pulmonary Medicine, Faculty of Medicine, Gaziantep University, Gaziantep 27310, Türkiye
Onder Ozturk
Department of Pulmonary Medicine, Faculty of Medicine, Suleyman Demirel University, Isparta 32260, Türkiye
Ilknur Basyigit
Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, Kocaeli 41380, Türkiye
Hasim Boyaci
Department of Pulmonary Medicine, Faculty of Medicine, Kocaeli University, Kocaeli 41380, Türkiye
Emel Azak
Department of Infectious Disease and Clinical Microbiology, Faculty of Medicine, Kocaeli University, Kocaeli 41380, Türkiye
Tansu Ulukavak Ciftci
Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye
Ipek Kivilcim Oguzulgen
Department of Pulmonary Medicine, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye
Hasan Selcuk Ozger
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye
Pinar Aysert Yildiz
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Gazi University, Ankara 06500, Türkiye
Ismail Hanta
Department of Pulmonary Medicine, Faculty of Medicine, Cukurova University, Adana 01790, Türkiye
Ozlem Ataoglu
Department of Pulmonary Medicine, Faculty of Medicine, Duzce University, Duzce 81620, Türkiye
Merve Ercelik
Department of Pulmonary Medicine, Faculty of Medicine, Duzce University, Duzce 81620, Türkiye
Caglar Cuhadaroglu
Department of Pulmonary Medicine, Altunizade Acibadem Hospital, Istanbul 34662, Türkiye
Hacer Kuzu Okur
Department of Pulmonary Medicine, Altunizade Acibadem Hospital, Istanbul 34662, Türkiye
Muge Meltem Tor
Department of Pulmonary Medicine, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak 67100, Türkiye
Esra Nurlu Temel
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Suleyman Demirel University, Isparta 32260, Türkiye
Seval Kul
Department of Biostatistics, Faculty of Medicine, Gaziantep University, Gaziantep 27310, Türkiye
Yıldız Tutuncu
Department of Immunology, Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University Istanbul, Istanbul 34010, Türkiye
Oya Itil
Department of Pulmonary Medicine, Faculty of Medicine, Dokuz Eylul University, Izmir 35340, Türkiye
Hasan Bayram
Koc University Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul 34010, Türkiye
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.