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 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, T Cells, Cytokines and Immunotherapy: Review

2021 ◽  
pp. 70-82
Author(s):  
Nesrin I. Tarbiah
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Viral Infections ◽  
Cytotoxic T Cells ◽  
Clinical Findings ◽  
Global Pandemic ◽  
Significant Step ◽  
Novel Coronavirus ◽  
Cellular Immune ◽  
Cell Expression

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus (COVID-19), materialized in the city of Wuhan and quickly spread to form a global pandemic. An essential role in the immune system is undertaken by lymphocytes, which defend against bacteria, viruses, fungi, and parasites. Previous study found that very severe COVID-19 patients had suppression of the immune response enabling the virus to spread and cause more damage. This was evident by the changes in their white blood cell and lymphocyte count. Early clinical findings suggest that those suffering from severe COVID-19 have reduced numbers of lymphocytes, monocytes, and other granulocytes. One of the most efficient responses for a variety of viral infections is cellular immune response activation, especially via T cells. Viruses can be eliminated by T cytotoxic (CD8+) (Tc) in the host body, these secrete a variety of molecules, including interferons (IFNs), granzyme, and perforin. T helper (CD4+) (Th) cells help by assisting cytotoxic T cells and B cells to eliminate viral infection. CD8+ and CD4+ work together in a coordinated immune response with other constituents to primarily resolve acute viral infections, and after to produce protection against any reinfection. Also, COVID-19 causes dramatic changes in cytokine profiles and serological markers. Therefore, the subsets of immune cells and the level of the pro-inflammatory cytokines are crucial evidence to determine the severity of COVID-19. The disease severity has already been proved to be associated with the disruption in the proinflammatory chemokine response, this eventually leads to a cytokine storm and progression of cytokines release syndrome (CRS). This review aimed to demonstrate a full understanding of the alterations to the immune response by determining the T-cell expression and cytokine levels against the pathological processes of COVID-19, which can be a significant step in early treatment and diagnosis of this disease, in reduction of COVID-19 mortality cases, and to emphasize the most recent and current studies to try to identify new immuno-therapeutics for 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 Cytokine storm interference

2021 ◽  
Vol 4 (1) ◽  
pp. 185-187
Author(s):  
Michael John Dochniak
Keyword(s):  
Innate Immunity ◽  
Acute Respiratory Distress Syndrome ◽  
Immune System ◽  
Innate Immune System ◽  
Distress Syndrome ◽  
Viral Infections ◽  
Acute Infection ◽  
Innate Immune ◽  
Cytokine Storm ◽  
Healthy Individuals

Viral infections are a natural and inevitable part of life. In healthy individuals, mortality increases when the body’s innate immune system quickly activates, creating a cytokine storm. A rapid and excessive release of cytokines into the bloodstream can cause acute respiratory distress syndrome and death. This communication proposes inhibiting cytokine storm development through forced atopy. Hyper-allergenic skin cream therapy stimulates adaptive immunity to support innate immunity before acute infection.

scholarly journals Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects

2021 ◽  
Vol 12 ◽  
Author(s):  
Barbara Gierlikowska ◽  
Albert Stachura ◽  
Wojciech Gierlikowski ◽  
Urszula Demkow
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Current Knowledge ◽  
Innate Immune ◽  
Therapeutic Approaches ◽  
Effector Functions ◽  
Pharmacological Modulation ◽  
Synthetic Drugs ◽  
Extracellular Traps

Neutrophils are crucial elements of innate immune system, which assure host defense via a range of effector functions, such as phagocytosis, degranulation, and NET formation. The latest literature clearly indicates that modulation of effector functions of neutrophils may affect the treatment efficacy. Pharmacological modulation may affect molecular mechanisms activating or suppressing phagocytosis, degranulation or NET formation. In this review, we describe the role of neutrophils in physiology and in the course of bacterial and viral infections, illustrating the versatility and plasticity of those cells. This review also focus on the action of plant extracts, plant-derived compounds and synthetic drugs on effector functions of neutrophils. These recent advances in the knowledge can help to devise novel therapeutic approaches via pharmacological modulation of the described processes.

Alternative medicine as a treatment options for COVID-19

2021 ◽  
Vol 07 ◽  
Author(s):  
Mahfuza Marzan ◽  
Md. Shahedur Rahman ◽  
Md. Abu Hena Mostofa Jamal ◽  
Mohammad Hossain Shariare ◽  
Md. Anowar Khasru Parvez
Keyword(s):  
Health Care ◽  
Vitamin D ◽  
Distress Syndrome ◽  
Scientific Evidence ◽  
Treatment Options ◽  
Viral Disease ◽  
Global Pandemic ◽  
Medicinal Properties ◽  
Mode Of Transmission ◽  
High Infectivity

: COVID-19, a viral disease caused by SARS-CoV-2 is the reason of a global pandemic since the starting of the year 2020. The characteristic of the disease varies from mild common cold like symptoms to acute respiratory distress syndrome and multi-organ failure leading to death. World has already observed 213,453 deaths from this disease while 3,095,839 have been infected in 210 countries in total till 28 April, 2020. This disease has a devastating impact over the health care system because of its high infectivity, easy mode of transmission, lack of proper medicine and vaccine and deficiency of enough supportive healthcare arrangement. On verge of this situation scientists are searching the treatment options. However, nature has provided us with enormous herbs which have disease preventive as well as have medicinal properties. In this article we have reviewed several of these plants (ginger, clove, tea, black seed, tulsi, neem) and some vitamins (vitamin C and vitamin D) and zinc which have antiviral, anti-inflammatory, antioxidant, anti-asthmatic properties with scientific evidence. The intake of these products regularly to keep the immune system active, to experience its positive aspects might be supportive to prevent infection with the new coronavirus or to treat COVID-19.

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 The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
De Novo ◽  
Current Knowledge ◽  
Innate Immune ◽  
De Novo Mutation ◽  
Neuronal Diversity ◽  
Alu Sequences ◽  
Pol Iii ◽  
The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

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