An Immune Cell Atlas Reveals Dynamic COVID-19 Specific Neutrophil Programming Amenable to Dexamethasone Therapy

Sinha, Sarthak; Rosin, Nicole L.; Arora, Rohit; Labit, Elodie; Jaffer, Arzina; Cao, Leslie; Farias, Raquel; Nguyen, Antoinette; McDonald, Braedon; Gillrie, Mark R.; Fritzler, Marvin J.; Yipp, Bryan G.; Biernaskie, Jeff

doi:10.1101/2021.04.18.440366

Cited by 3 publications

(1 citation statement)

References 66 publications

(110 reference statements)

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“…Several clinical trials have been carried out to study dexamethasone's therapeutic effect on COVID-19 infection. Many results have proved that it can regulate inflammation-mediated lung injury (Horby et al, 2021), thereby reducing the progress of respiratory failure and death; at the same time, attention has been paid to its positive effect on neutrophil aggregation and interferon system imbalance caused by COVID-19 (Sinha et al, 2022). Moreover, as has been shown by drug tests in human cell lines and human lower respiratory organoids, tretinoin, as a derivative of vitamin A, has antiviral activity against all SARS-COV-2 antibodies (Tong et al, 2022).…”

Section: Figurementioning

confidence: 99%

Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 on metabolic unhealthy obese patients

Huang,

Jiang,

Song

et al. 2023

Front. Mol. Biosci.

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Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has posed a significant challenge to individuals’ health. Increasing evidence shows that patients with metabolic unhealthy obesity (MUO) and COVID-19 have severer complications and higher mortality rate. However, the molecular mechanisms underlying the association between MUO and COVID-19 are poorly understood.Methods: We sought to reveal the relationship between MUO and COVID-19 using bioinformatics and systems biology analysis approaches. Here, two datasets (GSE196822 and GSE152991) were employed to extract differentially expressed genes (DEGs) to identify common hub genes, shared pathways, transcriptional regulatory networks, gene-disease relationship and candidate drugs.Results: Based on the identified 65 common DEGs, the complement-related pathways and neutrophil degranulation-related functions are found to be mainly affected. The hub genes, which included SPI1, CD163, C1QB, SIGLEC1, C1QA, ITGAM, CD14, FCGR1A, VSIG4 and C1QC, were identified. From the interaction network analysis, 65 transcription factors (TFs) were found to be the regulatory signals. Some infections, inflammation and liver diseases were found to be most coordinated with the hub genes. Importantly, Paricalcitol, 3,3′,4,4′,5-Pentachlorobiphenyl, PD 98059, Medroxyprogesterone acetate, Dexamethasone and Tretinoin HL60 UP have shown possibility as therapeutic agents against COVID-19 and MUO.Conclusion: This study provides new clues and references to treat both COVID-19 and MUO.

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Section: Figurementioning

confidence: 99%

Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 on metabolic unhealthy obese patients

Huang,

Jiang,

Song

et al. 2023

Front. Mol. Biosci.

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A functionally distinct neutrophil landscape in severe COVID-19 reveals opportunities for adjunctive therapies

Panda

Castanheira

Schlechte

et al. 2021

Preprint

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Acute respiratory distress syndrome (ARDS) is a life-threatening syndrome of respiratory failure and diffuse alveolar damage that results from dysregulated local and systemic immune activation, causing pulmonary vascular, parenchymal and alveolar damage. SARS-CoV-2 infection has become the dominant cause of ARDS worldwide, and emerging evidence implicates neutrophils and their cytotoxic arsenal of effector functions as central drivers of immune-mediated lung injury in COVID-19 ARDS. However, a key outstanding question is whether COVID-19 drives a unique program of neutrophil activation or effector functions that contributes to the severe pathogenesis of this pandemic illness, and whether this unique neutrophil response can be targeted to attenuate disease. Using a combination of high-dimensional single cell analysis and ex vivo functional assays of neutrophils from patients with COVID-19 ARDS compared to non-COVID ARDS (caused by bacterial pneumonia), we identified a functionally distinct landscape of neutrophil activation in COVID-19 ARDS that was intrinsically programmed during SARS-CoV-2 infection. Furthermore, neutrophils in COVID-19 ARDS were functionally primed to produce high amounts of neutrophil extracellular traps (NETs). Surprisingly, this unique pathological program of neutrophil priming escaped conventional therapy with dexamethasone, thereby revealing a promising target for adjunctive immunotherapy in severe COVID-19.

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Immune Profiling of COVID-19 in Correlation with SARS and MERS

Khalil

Shakartalla

Goel

et al. 2022

Viruses

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Acute respiratory distress syndrome (ARDS) is a major complication of the respiratory illness coronavirus disease 2019, with a death rate reaching up to 40%. The main underlying cause of ARDS is a cytokine storm that results in a dysregulated immune response. This review discusses the role of cytokines and chemokines in SARS-CoV-2 and its predecessors SARS-CoV and MERS-CoV, with particular emphasis on the elevated levels of inflammatory mediators that are shown to be correlated with disease severity. For this purpose, we reviewed and analyzed clinical studies, research articles, and reviews published on PubMed, EMBASE, and Web of Science. This review illustrates the role of the innate and adaptive immune responses in SARS, MERS, and COVID-19 and identifies the general cytokine and chemokine profile in each of the three infections, focusing on the most prominent inflammatory mediators primarily responsible for the COVID-19 pathogenesis. The current treatment protocols or medications in clinical trials were reviewed while focusing on those targeting cytokines and chemokines. Altogether, the identified cytokines and chemokines profiles in SARS-CoV, MERS-CoV, and SARS-CoV-2 provide important information to better understand SARS-CoV-2 pathogenesis and highlight the importance of using prominent inflammatory mediators as markers for disease diagnosis and management. Our findings recommend that the use of immunosuppression cocktails provided to patients should be closely monitored and continuously assessed to maintain the desirable effects of cytokines and chemokines needed to fight the SARS, MERS, and COVID-19. The current gap in evidence is the lack of large clinical trials to determine the optimal and effective dosage and timing for a therapeutic regimen.

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An Immune Cell Atlas Reveals Dynamic COVID-19 Specific Neutrophil Programming Amenable to Dexamethasone Therapy

Cited by 3 publications

References 66 publications

Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 on metabolic unhealthy obese patients

Bioinformatics and system biology approach to identify the influences of SARS-CoV-2 on metabolic unhealthy obese patients

A functionally distinct neutrophil landscape in severe COVID-19 reveals opportunities for adjunctive therapies

Immune Profiling of COVID-19 in Correlation with SARS and MERS

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