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

Kayalar, Ozgecan; Cetinkaya, Pelin; ELDEM, Vahap; ARGUN BARIŞ, SERAP; KÖKTÜRK, NURDAN; Kuralay, Selim; Rajabi, Hadi; Konyalilar, Nur; Mortazavi, Deniz; Korkunc, Seval; Erkan, Sinem; Aksoy, Gizem; Eyikudamaci, Gul; Pinar Deniz, Pelin; Baydar Toprak, Oya; Yildiz Gulhan, Pinar; Sagcan, Gulseren; Kose, Neslihan; Tomruk Erdem, Aysegul; Fakili, Fusun; Ozturk, Onder; Basyigit, İLKNUR; Boyaci, HAŞİM; Azak, EMEL; Ulukavak Ciftci, Tansu; Oguzulgen, Ipek; Ozger, Hasan; Aysert Yildiz, Pinar; Hanta, Ismail; Ataoglu, Ozlem; Ercelik, Merve; Cuhadaroglu, Caglar; Okur, Hacer; Tor, Muge; Nurlu Temel, Esra; Kul, Seval; Tutuncu, Yıldız; Itil, Oya; Bayram, Hasan

doi:10.3390/v16081211

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

Atıf İçin Kopyala

Kayalar O., Cetinkaya P. D., ELDEM V., ARGUN BARIŞ S., KÖKTÜRK N., Kuralay S. C., ...Daha Fazla

Viruses, cilt.16, sa.8, 2024 (SCI-Expanded)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 16 Sayı: 8
Basım Tarihi: 2024
Doi Numarası: 10.3390/v16081211
Dergi Adı: Viruses
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
Anahtar Kelimeler: COVID-19, inflammatory responses, long-term effects, peripheral blood mononuclear cells (PBMC), pneumonia, transcriptomic analysis
Kocaeli Üniversitesi Adresli: Evet

Özet

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.