scholarly journals COVID-19: Lung-Centric Immunothrombosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Peter R. Kvietys ◽  
Hana. M. A. Fakhoury ◽  
Sana Kadan ◽  
Ahmed Yaqinuddin ◽  
Eid Al-Mutairy ◽  
...  
Keyword(s):  
Pulmonary Infection ◽  
Distress Syndrome ◽  
Cytokine Production ◽  
Coagulation Factors ◽  
Innate Immune ◽  
Defensive Strategy ◽  
Extracellular Traps ◽  
Cytoplasmic Material ◽  
Activated Platelets ◽  
Activated Neutrophils

The respiratory tract is the major site of infection by SARS-CoV-2, the virus causing COVID-19. The pulmonary infection can lead to acute respiratory distress syndrome (ARDS) and ultimately, death. An excessive innate immune response plays a major role in the development of ARDS in COVID-19 patients. In this scenario, activation of lung epithelia and resident macrophages by the virus results in local cytokine production and recruitment of neutrophils. Activated neutrophils extrude a web of DNA-based cytoplasmic material containing antimicrobials referred to as neutrophil extracellular traps (NETs). While NETs are a defensive strategy against invading microbes, they can also serve as a nidus for accumulation of activated platelets and coagulation factors, forming thrombi. This immunothrombosis can result in occlusion of blood vessels leading to ischemic damage. Herein we address evidence in favor of a lung-centric immunothrombosis and suggest a lung-centric therapeutic approach to the ARDS of COVID-19.

scholarly journals COVID–19-associated coagulopathy: An exploration of mechanisms

2020 ◽  
Vol 25 (5) ◽  
pp. 471-478 ◽  
Author(s):  
Meaghan E Colling ◽  
Yogendra Kanthi
Keyword(s):  
Distress Syndrome ◽  
Viral Infections ◽  
Degradation Products ◽  
Clinical Findings ◽  
Innate Immune ◽  
Clotting Factors ◽  
Extracellular Traps ◽  
Activated Platelets ◽  
Global Pandemic ◽  
Active Investigation

An ongoing global pandemic of viral pneumonia (coronavirus disease [COVID-19]), due to the virus SARS-CoV-2, has infected millions of people and remains a threat to many more. Most critically ill patients have respiratory failure and there is an international effort to understand mechanisms and predictors of disease severity. Coagulopathy, characterized by elevations in D-dimer and fibrin(ogen) degradation products (FDPs), is associated with critical illness and mortality in patients with COVID-19. Furthermore, increasing reports of microvascular and macrovascular thrombi suggest that hemostatic imbalances may contribute to the pathophysiology of SARS-CoV-2 infection. We review the laboratory and clinical findings of patients with COVID–19-associated coagulopathy, and prior studies of hemostasis in other viral infections and acute respiratory distress syndrome. We hypothesize that an imbalance between coagulation and inflammation may result in a hypercoagulable state. Although thrombosis initiated by the innate immune system is hypothesized to limit SARS-CoV-2 dissemination, aberrant activation of this system can cause endothelial injury resulting in loss of thromboprotective mechanisms, excess thrombin generation, and dysregulation of fibrinolysis and thrombosis. The role various components including neutrophils, neutrophil extracellular traps, activated platelets, microparticles, clotting factors, inflammatory cytokines, and complement play in this process remains an area of active investigation and ongoing clinical trials target these different pathways in COVID-19.

scholarly journals Innate immune deficiencies are associated with severity and poor prognosis in patients with COVID-19

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Marine Peyneau ◽  
Vanessa Granger ◽  
Paul-Henri Wicky ◽  
Dounia Khelifi-Touhami ◽  
Jean-François Timsit ◽  
...  
Keyword(s):  
Distress Syndrome ◽  
Innate Immune ◽  
Activation Markers ◽  
Extracellular Traps ◽  
Hla Dr ◽  
Immune Deficiencies ◽  
Severe Infections ◽  
Monocyte Subpopulations ◽  
Critical Patients

AbstractCOVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.

scholarly journals Targeting potential drivers of COVID-19: Neutrophil extracellular traps

2020 ◽  
Vol 217 (6) ◽  
Author(s):  
Betsy J. Barnes ◽  
Jose M. Adrover ◽  
Amelia Baxter-Stoltzfus ◽  
Alain Borczuk ◽  
Jonathan Cools-Lartigue ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Cytokine Production ◽  
Neutrophil Extracellular Traps ◽  
Organ Damage ◽  
Clinical Severity ◽  
Pulmonary Diseases ◽  
Cytokine Storm ◽  
Extracellular Traps ◽  
Autopsy Specimen

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10–15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils—the ability to form neutrophil extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.

scholarly journals NETs and oncologic process

2021 ◽  
Vol 15 (1) ◽  
pp. 107-116
Author(s):  
E. V. Slukhanchuk
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Activated Neutrophils ◽  
Autoimmune Conditions

Neutrophil Extracellular Traps (NETs) represent the networks consisting of DNA, histones, and proteins produced by activated neutrophils. Such structures have been proved to play a crucial role in inducing neutrophil innate immune response in the pathogenesis of such autoimmune conditions as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, as well as in the pathogenesis of other non-infectious processes, e. g., clotting disorders, thrombosis, diabetes, atherosclerosis, vasculitis and oncology diseases. Recent studies on animal models and human pathologies have uncovered a tremendous role for NETs in tumor progression and metastasis. In this regard, NETs should be considered as pro-oncogenic substances, which further investigation will provide an opportunity to develop new therapeutic strategies.

scholarly journals Supercharged eGFP-TRAIL Decorated NETs to Ensnare and Kill Disseminated Tumor Cells

2020 ◽  
Vol 13 (4) ◽  
pp. 359-367
Author(s):  
Thong M. Cao ◽  
Michael R. King
Keyword(s):  
Tumor Cells ◽  
Chimeric Protein ◽  
Disseminated Tumor Cells ◽  
Innate Immune ◽  
Delivery Vehicle ◽  
Extracellular Traps ◽  
Microbial Infections ◽  
Activated Neutrophils ◽  
Tumor Drug Delivery ◽  
Induced Apoptosis

Abstract Background NETosis is an innate immune response elicited by activated neutrophils to fight microbial infections. Activated neutrophils release DNA fibers decorated with anti-microbial proteins called neutrophil extracellular traps (NETs) into the extracellular space to trap and kill surrounding microbes. Methods Here, we show that tumor-derived IL-8 released by cancer cells also activates the release of NETs. Until now, there have been no existing technologies that leverage NETs as an anti-tumor drug delivery vehicle. In this study, we demonstrate the re-engineering of neutrophils to express an apoptosis-inducing chimeric protein, supercharged eGFP-TRAIL, on NETs that can ensnare and kill tumor cells while retaining their anti-microbial capabilities. Results We observed significant TRAIL-induced apoptosis in tumor cells captured by TRAIL-decorated NETs. Conclusions This work demonstrates NETs as a promising technology to deliver protein in response to local cytokine signals.

Decreased mean platelet volume is associated with microsatellite instability in colorectal cancer: A propensity score-matched analysis

2021 ◽  
pp. 1-9
Author(s):  
Wen Wang ◽  
Guangyu Wang ◽  
Shuang Fu ◽  
Beibei Zhang ◽  
Zengyao Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Propensity Score ◽  
Microsatellite Instability ◽  
Propensity Score Matching ◽  
Mean Platelet Volume ◽  
Innate Immune ◽  
Platelet Volume ◽  
Activated Platelets ◽  
Medical University ◽  
Potential Parameters

BACKGROUND: Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis and a more effective immune response than patients with microsatellite stable (MSS) CRC. Moreover, activated platelets play a crucial role in modulating innate immune cells. Mean platelet volume (MPV) is an indicator of platelet activation. This study is to examine the association between MPV and MSI status in CRC. METHODS: We collected the clinical and pathological variables of 424 CRC patients diagnosed at the Harbin Medical University Cancer Hospital from January 2018 to December 2018. Associations between MPV levels and MSI status were examined. Propensity score matching (PSM) was performed to reduce the possibility of selection bias. RESULTS: 424 CRC patients were divided into low-MPV group and high-MPV group according to the optimal cut-off value of MPV. 131 high-MPV patients were matched to low-MPV counterparts in a 1:1 ratio by propensity score matching. As MPV levels increased, the percentage of patients with MSI-H reduced. Furthermore, compared with MSS group, the MSI-H group had a significantly lower MPV levels (p= 0.003 after matching). In addition, logistic regression analysis identified reduced MPV as an independent risk factor for MSI-H in CRC patients after controlling for other potential parameters. CONCLUSION: Lower MPV is associated with MSI-H subtype of CRC. Further study on MPV in MSI-H CRC is warranted.

scholarly journals Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 53
Author(s):  
Anjali Trivedi ◽  
Meraj A. Khan ◽  
Geetanjali Bade ◽  
Anjana Talwar
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Mucus Production ◽  
Obstructive Pulmonary Disease ◽  
Extracellular Traps ◽  
Endothelial Cell Death

Morbidity, mortality and economic burden caused by chronic obstructive pulmonary disease (COPD) is a significant global concern. Surprisingly, COPD is already the third leading cause of death worldwide, something that WHO had not predicted to occur until 2030. It is characterized by persistent respiratory symptoms and airway limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles of gases. Neutrophil is one of the key infiltrated innate immune cells in the lung during the pathogenesis of COPD. Neutrophils during pathogenic attack or injury decide to undergo for a suicidal death by releasing decondensed chromatin entangled with antimicrobial peptides to trap and ensnare pathogens. Casting neutrophil extracellular traps (NETs) has been widely demonstrated to be an effective mechanism against invading microorganisms thus controlling overwhelming infections. However, aberrant and massive NETs formation has been reported in several pulmonary diseases, including chronic obstructive pulmonary disease. Moreover, NETs can directly induce epithelial and endothelial cell death resulting in impairing pulmonary function and accelerating the progression of the disease. Therefore, understanding the regulatory mechanism of NET formation is the need of the hour in order to use NETs for beneficial purpose and controlling their involvement in disease exacerbation. For example, DNA neutralization of NET proteins using protease inhibitors and disintegration with recombinant human DNase would be helpful in controlling excess NETs. Targeting CXC chemokine receptor 2 (CXCR2) would also reduce neutrophilic inflammation, mucus production and neutrophil-proteinase mediated tissue destruction in lung. In this review, we discuss the interplay of NETs in the development and pathophysiology of COPD and how these NETs associated therapies could be leveraged to disrupt NETopathic inflammation as observed in COPD, for better management of the disease.

scholarly journals Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Melanie R. Neeland ◽  
Samantha Bannister ◽  
Vanessa Clifford ◽  
Kate Dohle ◽  
Kim Mulholland ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Acute Phase ◽  
Innate Immune ◽  
Low Density ◽  
Innate Immune Responses ◽  
Immunological Mechanisms ◽  
Activated Neutrophils ◽  
Classical Monocytes

AbstractChildren have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.

Sign in / Sign up

Export Citation Format

Share Document