Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19

Prebensen, Christian; Lefol, Yohan; Myhre, Peder L.; Lüders, Torben; Jonassen, Christine Monceyron; Blomfeldt, Anita; Omland, Torbjørn; Nilsen, Hilde; Berdal, Jan-Erik

doi:10.1038/s41598-023-37606-y

Cited by 10 publications

(5 citation statements)

References 57 publications

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“…It is to be determined if low interferon can correlate with the emergence of fibrosis post-COVID-19, but our data showed normalization at day seven [52]. Elevated granzyme B and H levels are part of the initial granulocyte response during non-specific immune system activation [53]. The immunological signatures described in this manuscript are complex and do not represent a simply interpretation.…”

Section: Discussionmentioning

confidence: 70%

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure

Laudanski,

Mahmoud,

Ahmed

et al. 2024

IJMS

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This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

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Section: Discussionmentioning

confidence: 70%

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure

Laudanski,

Mahmoud,

Ahmed

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Among the 13 datasets, 11 datasets were downloaded from gene expression omnibus (GEO, , accessed on 15 May 2023), 1 dataset was downloaded from the Zenodo repository ( , accessed on 15 May 2023), and 1 more was downloaded from the genome sequence archive (GSA, , accessed on 15 May 2023). The accession numbers were GSE152641 [ 9 ], GSE161731 [ 10 ], GSE161777 [ 11 ], GSE171110 [ 12 ], GSE179850 [ 13 ], GSE185557 [ 14 ], GSE189990 [ 15 ], GSE196822 [ 16 ], GSE213313 [ 17 ], GSE217948 [ 18 ], GSE223885 [ 19 ], Zenodo 6120249 [ 20 ], and HRA000238 [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Hypoxia and Activation of Neutrophil Degranulation-Related Genes in the Peripheral Blood of COVID-19 Patients

Lei

2024

Viruses

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Severe COVID-19 is characterized by systematic hyper-inflammation and subsequent damage to various organs. Therefore, it is critical to trace this cascade of hyper-inflammation. Blood transcriptome has been routinely utilized in the interrogation of host immune response in COVID-19 and other infectious conditions. In this study, consensus gene dysregulation in the blood was obtained from 13 independent transcriptome studies on COVID-19. Among the up-regulated genes, the most prominent functional categories were neutrophil degranulation and cell cycle, which is clearly different from the classical activation of interferon signaling pathway in seasonal flu. As for the potential upstream causal factors of the atypical gene dysregulation, systemic hypoxia was further examined because it is much more widely reported in COVID-19 than that in seasonal flu. It was found that both physiological and pathological hypoxia can induce activation of neutrophil degranulation-related genes in the blood. Furthermore, COVID-19 patients with different requirement for oxygen intervention showed distinctive levels of gene expression related to neutrophil degranulation in the whole blood, which was validated in isolated neutrophils. Thus, activation of neutrophil degranulation-related genes in the blood of COVID-19 could be partially attributed to hypoxia. Interestingly, similar pattern was also observed in H1N1 infection (the cause of Spanish flu) and several other severe respiratory viral infections. As for the molecular mechanism, both HIF-dependent and HIF-independent pathways have been examined. Since the activation of neutrophil degranulation-related genes is highly correlated with disease severity in COVID-19, early detection of hypoxia and active intervention may prevent further activation of neutrophil degranulation-related genes and other harmful downstream hyper-inflammation. This common mechanism is applicable to current and future pandemic as well as the severe form of common respiratory infection.

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“…The ID GSE213313 dataset was from the Agilent-072363 SurePrint G3 Human GE v3 8 × 60K Microarray 039494 (GPL21185) platform, and contains 34 COVID-19 samples and 11 healthy control samples. [18] The ID GSE131761 dataset was from the Agilent-026652 Whole Human Genome Microarray 4 × 44K v2 (GPL13497) platform, and contains 81 septic shock samples and 15 healthy control samples. [19] These datasets were used to verify the mRNA expression of hub genes and for ROC analysis.…”

Section: Validation and Receiver Operating Characteristic Curve Analy...mentioning

confidence: 99%

Identification of key regulatory genes in the pathogenesis of COVID-19 and sepsis: An observational study

Chen,

Yang,

Luo

2024

Medicine

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Patients with severe COVID-19 and those with sepsis have similar clinical manifestations. We used bioinformatics methods to identify the common hub genes in these 2 diseases. Two RNA-seq datasets from the Gene Expression Omnibus were used to identify common differentially expressed genes (DEGs) in COVID-19 and sepsis. These common genes were used for analysis of functional enrichment; pathway analysis; identification of associated transcription factors, metabolites, and miRNAs; and mapping of protein–protein interaction networks. The major hub genes of COVID-19 and sepsis were identified, and validation datasets were used to assess the value of these hub genes using receiver operating characteristic (ROC) curves. Analysis of the 800 common DEGs for COVID-19 and sepsis, as well as common transcription factors, miRNAs, and metabolites, demonstrated that the immune response had a key role in both diseases. DLGAP5, BUB1, CDK1, CCNB1, and BUB1B were the most important common hub genes. Analysis of a validation cohort indicated these 5 genes had significantly higher expression in COVID-19 patients and sepsis patients than in corresponding controls, and the area under the ROC curves ranged from 0.832 to 0.981 for COVID-19 and 0.840 to 0.930 for sepsis. We used bioinformatics tools to identify common DEGs, miRNAs, and transcription factors for COVID-19 and sepsis. The 5 identified hub genes had higher expression in validation cohorts of COVID-19 and sepsis. These genes had good or excellent diagnostic performance based on ROC analysis, and therefore have potential use as novel markers or therapeutic targets.

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Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19

Cited by 10 publications

References 57 publications

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure

Immunological Signatures in Blood and Urine in 80 Individuals Hospitalized during the Initial Phase of COVID-19 Pandemic with Quantified Nicotine Exposure

Hypoxia and Activation of Neutrophil Degranulation-Related Genes in the Peripheral Blood of COVID-19 Patients

Identification of key regulatory genes in the pathogenesis of COVID-19 and sepsis: An observational study

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