Analysis of cytokines in SARS-CoV-2 or COVID-19 patients in Erbil city, Kurdistan Region of Iraq

Merza, Mohammed; Hwaiz, Rundk; Hamad, B; Mohammad, Karzan Abdulmuhsin; Hama, Harmand A.; Karim, Abdulkarim Yasin

doi:10.1371/journal.pone.0250330

Cited by 54 publications

(44 citation statements)

References 17 publications

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“…Regarding cytokine production, many cytokines and chemokines have been evaluated to improve patient management and enable a targeted personalized approach. Overproduction of the proin ammatory cytokines IL-1, IL-6, IL-8 and TNF-α and low of expression IFN-γ have been found in severe COVID-19 patients [9,10] Another proin ammatory cytokine, IL-32, activates signalling pathways of mitogen-activated protein kinases (MAPKs) and of nuclear factor (NF)-κB. It is produced by various epithelial and immune cells such as T lymphocytes, NK cells and monocytes.…”

Section: Introductionmentioning

confidence: 99%

Cytokine Profiles in the Detection of Severe Lung Involvement in Hospitalized Patients With COVID-19: the IL-8 – IL-32 axis

Bergantini

d’Alessandro

Cameli

et al. 2021

Preprint

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Coronavirus disease 2019 (COVID-19) is an infectious respiratory disorder caused by a new coronavirus called SARS-CoV-2. The pathophysiology of severe COVID-19 is associated with a “cytokine storm”, characterized by anomalous release of various pro-inflammatory cytokines which contribute to alveolar exudation and lung damage. Overproduction of the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-α and low of expression IFN-γ have been found in severe COVID-19 patients. The mechanism by which IL-32 exerts its signalling properties is unclear. IL-32 is a key modulator in the pathogenesis of various clinical conditions and is mostly induced by IL-8. IL-32 modulates important inflammatory pathways (including TNF-α, IL-6 and IL-1b), contributing to the pathogenesis of inflammatory diseases. A total of 64 COVID-19 patients, stratifying as mild moderate and severe patients and 27 healthy controls were consecutively enrolled in the study. Serum concentrations of biomarkers including IL-1β, IL-10, IFN-γ, TNF-α and IL-6 were quantified by bead-based multiplex analysis and Serum concentration of IL-8 and IL-32 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, among the blood parameters, neutrophil and lymphocyte counts were significantly lower in severe COVID-19 patients than in the other, on the contrary, CRP was significantly higher in severe patients than in other groups. The cytokines that best distinguished controls from COVID-19 patients were IL-8 and IL-32.The best model performance for severe group was obtained by the combination of IL-32, IL-6 and IFN-γ, and serum concentrations of CRP increased model performance, showing AUC=0.83. New insights into the cytokine storm in COVID-19 patients, highlighting specific cytokine signatures among patients with different severity of infection.

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Section: Introductionmentioning

confidence: 99%

Cytokine Profiles in the Detection of Severe Lung Involvement in Hospitalized Patients With COVID-19: the IL-8 – IL-32 axis

Bergantini

d’Alessandro

Cameli

et al. 2021

Preprint

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“…The CytokineLink analysis provides a possible mechanistic link to the lack of one of the key anti-inflammatory cytokines, IL12. The low levels of IL12 are comparable to healthy controls in severe COVID-19 patients, while the levels of IL4 are significantly higher in severe patients [38,39]. We note that the basis of using IL4 to complement the system was based on our previous work involving literature curation.…”

Section: Resultsmentioning

confidence: 97%

“…The IL4 - IL12 interaction is highlighted with dashed lines. IL4 has been shown to be increased in severe COVID-19, potentially repressing IL12, whose levels are comparable to healthy controls in severe cases [38,39]. Mutual edges were collapsed, shown with arrows on both ends to reduce complexity.…”

Section: Resultsmentioning

confidence: 99%

CytokineLink: a cytokine communication map to analyse immune responses in inflammatory and infectious diseases

Ölbei

Thomas

Hautefort

et al. 2021

Preprint

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Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine - cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from literature, and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated literature information on cell - cytokine interactions from two systems immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell-cell communication network connected by cytokines; and a cytokine-cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify inactive cell types and cytokine interactions that may be important following SARS-CoV-2 infection when comparing the cytokine response with other viruses capable of initiating a cytokine storm. Such findings have potential to inform the development of novel, cytokine-targeted therapeutic strategies. CytokineLink is freely available for the scientific community through the NDEx platform and the project github repository (https://github.com/korcsmarosgroup/CytokineLink).

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“…The CytokineLink analysis provides a possible mechanistic link to the lack of one of the key anti-inflammatory cytokines, IL12. The low levels of IL12 are comparable to healthy controls in severe COVID-19 patients, while the levels of IL4 are significantly higher in severe patients [ 37 , 38 ]. We note that the basis of using IL4 to complement the system was based on our previous work involving the literature curation.…”

Section: Resultsmentioning

confidence: 99%

“…The IL4-IL12 interaction is highlighted with dashed lines. IL4 is increased in severe COVID-19, potentially repressing IL12, whose levels are comparable to healthy controls in severe cases [ 37 , 38 ]. Mutual edges were collapsed, shown with arrows on both ends to reduce complexity.…”

Section: Figurementioning

confidence: 99%

CytokineLink: A Cytokine Communication Map to Analyse Immune Responses—Case Studies in Inflammatory Bowel Disease and COVID-19

Ölbei

Thomas

Hautefort

et al. 2021

Cells

View full text Add to dashboard Cite

Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine–cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from the literature and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated the literature information on cell–cytokine interactions from two systems of immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell–cell communication network connected by cytokines; and a cytokine–cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink, we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify cell types and cytokine interactions following SARS-CoV-2 infection, highlighting important cytokine interactions that might contribute to severe illness in a subgroup of patients. Such findings have the potential to inform the development of novel, cytokine-targeted therapeutic strategies. CytokineLink is freely available for the scientific community through the NDEx platform and the project github repository.

show abstract

Analysis of cytokines in SARS-CoV-2 or COVID-19 patients in Erbil city, Kurdistan Region of Iraq

Cited by 54 publications

References 17 publications

Cytokine Profiles in the Detection of Severe Lung Involvement in Hospitalized Patients With COVID-19: the IL-8 – IL-32 axis

Cytokine Profiles in the Detection of Severe Lung Involvement in Hospitalized Patients With COVID-19: the IL-8 – IL-32 axis

CytokineLink: a cytokine communication map to analyse immune responses in inflammatory and infectious diseases

CytokineLink: A Cytokine Communication Map to Analyse Immune Responses—Case Studies in Inflammatory Bowel Disease and COVID-19

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