Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 30, 2021

The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to failure multi-organ or death. pathogenesis of SARS-CoV-2 infection is attributed a complex interplay between virus host immune response. It involves activation multiple inflammatory pathways leading hyperinflammation cytokine storm, resulting in tissue damage, distress (ARDS) failure. Accumulating evidence raised concern over long-term health effects COVID-19. Importantly, neuroinvasive potential may have consequences brain. This review provides conceptual framework on how tricks system induce cause disease. We also explore key differences mild COVID-19 its short- effects, particularly human

Language: Английский

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Interleukin-6, CXCL10 and Infiltrating Macrophages in COVID-19-Related Cytokine Storm: Not One for All But All for One!

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: April 26, 2021

SARS-COV-2 virus is responsible for the ongoing devastating pandemic. Since early phase of pandemic, "cytokine-storm" appeared a peculiar aspect infection which, at least in severe cases, respiratory treat damage and subsequent multi-organ failure. The efforts made last few months elucidated that cytokine-storm results from complex network involving cytokines/chemokines/infiltrating-immune-cells which orchestrate aberrant immune response COVID-19. Clinical experimental studies aimed depicting potential "immune signature" SARS-COV-2, identified three main "actors," namely cytokine IL-6, chemokine CXCL10 infiltrating cell type macrophages. Although other cytokines, chemokines cells are deeply involved their role should not be neglected, based on currently available data, CXCL10, macrophages could considered prototype factors representing each component system. It rapidly became clear strong continuous interplay among components mandatory order to produce clinical course disease. Indeed, while alone would able fully drive onset maintenance cytokine-storm, establishment IL-6/CXCL10/macrophages axis crucial driving sequence events characterizing this condition. present review specifically overviewing current evidences provided by both

Language: Английский

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Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis

Clinical Reviews in Allergy & Immunology, Journal Year: 2022, Volume and Issue: 64(1), P. 33 - 65

Published: Jan. 18, 2022

Language: Английский

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The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Feb. 23, 2022

Abstract The coronavirus disease 2019 (COVID-19) is a highly transmissible caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) that poses major threat to global public health. Although COVID-19 primarily affects system, causing pneumonia and distress in cases, it can also result multiple extrapulmonary complications. pathogenesis of damage patients with probably multifactorial, involving both direct effects SARS-CoV-2 indirect mechanisms associated host inflammatory response. Recognition features complications has clinical implications for identifying progression designing therapeutic strategies. This review provides an overview from immunological pathophysiologic perspectives focuses on potential targets management COVID-19.

Language: Английский

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SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(12), P. 2068 - 2079

Published: Nov. 2, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used model of viral infection macaques to address whether SARS-CoV-2 persists the body and which mechanisms regulate its persistence. Replication-competent virus was detected bronchioalveolar lavage (BAL) macrophages beyond 6 months Viral propagation BAL occurred from cell inhibited by interferon-γ (IFN-γ). IFN-γ production strongest NKG2r+CD8+ T cells NKG2Alo natural killer (NK) further increased NK spike protein stimulation. However, impaired with persisting virus. Moreover, also enhanced expression major histocompatibility complex (MHC)-E on macrophages, possibly inhibiting cell-mediated killing. Macaques less mounted adaptive that escaped MHC-E-dependent inhibition. Our findings reveal an interplay between regulated persistence mediated IFN-γ.

Language: Английский

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Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Pathogens, Journal Year: 2021, Volume and Issue: 10(5), P. 565 - 565

Published: May 7, 2021

The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for has been discovered. Recent investigations research studies primarily focus immunopathology disease. A healthy immune system responds immediately after viral entry, causing immediate annihilation recovery. However, an impaired causes extensive systemic damage due to unregulated response characterized hypersecretion chemokines cytokines. elevated levels cytokine or hypercytokinemia leads distress (ARDS) along with multiple organ damage. Moreover, against SARS-CoV-2 linked race, gender, age; hence, this infection's outcome differs among patients. Many therapeutic strategies focusing immunomodulation have tested assuage storm in patients COVID-19. thorough understanding diverse signaling pathways triggered virus essential before contemplating relief measures. This present review explains interrelationships hyperinflammatory severity. Furthermore, we thrown light mechanisms risk factors that influence molecular lead infection Recognition altered dysregulated can be loophole identify potential target markers. Identifying biomarkers pathway aid better clinical management COVID-19 special also given potent inhibitors proinflammatory cytokines, immunomodulatory immunotherapeutic options ameliorate inflammatory responses affected

Language: Английский

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Honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) Suppress SARS-CoV-2 Entry and COVID-19 Related Cytokine Storm in Vitro

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 12

Published: March 25, 2022

COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, not both. Traditional Chinese medicine (TCM) could be promising candidates due their safety and minimal toxicity. In study, we have developed a novel in silico bioinformatics workflow that integrates multiple databases predict use honeysuckle ( Lonicera japonica ) Huangqi Astragalus membranaceus as potential anti-SARS-CoV-2 agents. Using extracts from Huangqi, these two herbs upregulated group microRNAs including let-7a , miR-148b miR-146a which are critical reduce pathogenesis SARS-CoV-2. Moreover, suppressed pro-inflammatory cytokines IL-6 TNF-α, were both identified cytokine storm acute respiratory distress syndrome, major cause death. Furthermore, partially inhibited fusion SARS-CoV-2 spike protein-transfected BHK-21 cells with lung cancer cell line Calu-3 was expressing ACE2 receptors. These M pro activity, thereby alleviating entry well replication. conclusion, our findings demonstrate used an inhibitor virus warrants further vivo analysis functional assessment miRNAs confirm clinical importance. This fast-screening platform can also applied other drug discovery studies infectious diseases.

Language: Английский

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Self-supervised contrastive learning for integrative single cell RNA-seq data analysis

Briefings in Bioinformatics, Journal Year: 2022, Volume and Issue: 23(5)

Published: Sept. 1, 2022

We present a novel self-supervised Contrastive LEArning framework for single-cell ribonucleic acid (RNA)-sequencing (CLEAR) data representation and the downstream analysis. Compared with current methods, CLEAR overcomes heterogeneity of experimental specifically designed learning task thus can handle batch effects dropout events simultaneously. It achieves superior performance on broad range fundamental tasks, including clustering, visualization, correction, effect removal, pseudo-time inference. The proposed method successfully identifies illustrates inflammatory-related mechanisms in COVID-19 disease study 43 695 single cells from peripheral blood mononuclear cells.

Language: Английский

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The Role of Nuclear Factor Kappa B (NF-κB) in Development and Treatment of COVID-19: Review

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 5283 - 5283

Published: May 9, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 19 (COVID-19), a disease that has affected more than 500 million people worldwide since the end of 2019. Due to its high complications and death rates, there is still need find best therapy for SARS-CoV-2 infection. The dysregulation inflammatory response in COVID-19 plays very important role progression. It been observed abnormal activity Nuclear Factor kappa B (NF-κB) directly associated with, inter alia, increased synthesis proinflammatory factors. Therefore, this review paper focuses on functions NF-κB development infection potential application inhibitors immunotherapy. A comprehensive literature search was performed using MEDLINE/PubMed database. In current review, it highlighted modulation an adaptive response, including inducing expression genes. Increased activation observed. association between structural non-structural proteins were also reported. using, e.g., traditional Chinese medicine or glucocorticosteroids resulted decreased factors caused by This summarizes describes immunotherapeutic target treatment However, indisputably studies involving patients with severe course are sorely needed.

Language: Английский

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Biomarkers of the ageing immune system and their association with frailty – A systematic review

Experimental Gerontology, Journal Year: 2023, Volume and Issue: 176, P. 112163 - 112163

Published: April 15, 2023

Ageing is associated with several physiological changes, including changes in the immune system. Age-related innate and adaptive system are thought to contribute frailty. Understanding immunological determinants of frailty could help develop deliver more effective care older people. This systematic review aims study association between biomarkers ageing The search strategy was performed PubMed Embase, using keywords "immunosenescence", "inflammation", "inflammaging" "frailty". We included studies that investigated cross-sectionally adults, without an active disease affects parameters. Three independent researchers selected data extraction. Study quality assessed Newcastle-Ottawa scale adapted for cross-sectional studies. A total 44 studies, a median number 184 participants, included. good 16 (36 %), moderate 25 (57 %) poor 3 (7 most frequently studied inflammaging were IL-6, CRP TNF-α. Associations observed increased levels (i) IL-6 12 24 (ii) 7 19 TNF-α 4 13 In none other associations these biomarkers. Different types T-lymphocyte subpopulations but each subset only once, sample sizes low. Our on relation identified as consistently too infrequently draw strong conclusions yet, although initial results promising. Additional required order further validate larger cohorts. Furthermore, prospective uniform settings cohorts needed investigate candidate which potential previously observed, before can be used clinical practice assess improve treatments patients.

Language: Английский

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