scholarly journals Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?

2020 ◽  
Author(s):  
Ligong Lu ◽  
Hui Zhang ◽  
Meixiao Zhan ◽  
Jun Jiang ◽  
Hua Yin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Inflammatory Mediator ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
Critical Factors ◽  
Patient Death ◽  
Three Stages

Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.

scholarly journals Prospective approach to manage COVID-19-related cytokine storm; an updated review on current concepts

2021 ◽  
Vol 6 (1) ◽  
pp. e20-e20
Author(s):  
Mohaddeseh Bahmani ◽  
Lillian Saberian
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Cytokines ◽  
The Novel ◽  
Cytokine Storm ◽  
Human Coronavirus ◽  
Immune Imbalance ◽  
The City ◽  
Secondary Hemophagocytic Lymphohistiocytosis

Coronavirus disease 2019 or COVID-19, caused by the novel human coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in late 2019, in the city of Wuhan, Hubei province, China. Unfortunately, despite many efforts to find cures for SARS-CoV-2 disease, still the management of severe cases remains challenging. In severe forms of COVID-19, proinflammatory cytokines are notably elevated (3) and reminiscent of the secondary hemophagocytic lymphohistiocytosis (HLH). According to many studies, immune imbalance and an uncontrolled massive release of inflammatory cytokines have a significant role in COVID-19 severity and ARDS pathophysiology. Accordingly, targeting the over-activated immune system to prevent tissue damage is now one of the most noticed possible strategies to manage severe COVID-19 cases. In the present study, we reviewed studies and clinical trials conducted in this regard.

scholarly journals Functionalized Dendrimer Platforms as a New Forefront Arsenal Targeting SARS-CoV-2: An Opportunity

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1513
Author(s):  
Serge Mignani ◽  
Xiangyang Shi ◽  
Andrii Karpus ◽  
Giovanni Lentini ◽  
Jean-Pierre Majoral
Keyword(s):  
Clinical Trials ◽  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Cytokines ◽  
The Novel ◽  
Cytokine Storm ◽  
Human Coronavirus ◽  
Important Means ◽  
Inflammatory Drugs ◽  
Approved Drugs ◽  
Pro Inflammatory Cytokines

The novel human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused a pandemic. There are currently several marketed vaccines and many in clinical trials targeting SARS-CoV-2. Another strategy is to repurpose approved drugs to decrease the burden of the COVID-19 (official name for the coronavirus disease) pandemic. as the FDA (U.S. Food and Drug Administration) approved antiviral drugs and anti-inflammatory drugs to arrest the cytokine storm, inducing the production of pro-inflammatory cytokines. Another view to solve these unprecedented challenges is to analyze the diverse nanotechnological approaches which are able to improve the COVID-19 pandemic. In this original minireview, as promising candidates we analyze the opportunity to develop biocompatible dendrimers as drugs themselves or as nanocarriers against COVID-19 disease. From the standpoint of COVID-19, we suggest developing dendrimers as shields against COVID-19 infection based on their capacity to be incorporated in several environments outside the patients and as important means to stop transmission of SARS-CoV-2.

scholarly journals The LIFE CYCLE OF COVID-19 STAGES AND TREATMENT

2020 ◽  
Vol 9 (3) ◽  
Author(s):  
Ripu Daman M. Singh ◽  
Nida Malim ◽  
Aves Raza Khan ◽  
Huda Khan ◽  
Nauman Khatib ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Life Cycle ◽  
Severe Acute Respiratory Syndrome ◽  
Late Phase ◽  
Antiviral Drug ◽  
Cytokine Storm ◽  
Clinical Recovery ◽  
The World ◽  
Autoimmune Conditions ◽  
Viral Outbreak

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)bat viruses, therefore bats could be the possible primary reservoir , which emerged in Wuhan, China and spread around the world. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. We also discuss the approaches for  therapeutic combinations to cope with this viral outbreak. Chloroquine has been sporadically used in treating SARS-CoV-2 infection. Hydroxychloroquine shares the same mechanism of action as chloroquine, but its more tolerable safety profile makes it the preferred drug to treat malaria and autoimmune conditions. We propose that the immunomodulatory effect of hydroxychloroquine also may be useful in controlling the cytokine storm that occurs late-phase in critically ill SARS-CoV-2 infected patients.

scholarly journals Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

2021 ◽  
Vol 22 (15) ◽  
pp. 7914
Author(s):  
So Yeong Cheon ◽  
Bon-Nyeo Koo
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Response ◽  
Immune Complex ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Organ Damage ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Pro Inflammatory Cytokines

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.

scholarly journals COVID-19 Pathology on Various Organs and Regenerative Medicine and Stem Cell-Based Interventions

2021 ◽  
Vol 9 ◽  
Author(s):  
Babak Arjmand ◽  
Sepideh Alavi-Moghadam ◽  
Peyvand Parhizkar Roudsari ◽  
Mostafa Rezaei-Tavirani ◽  
Fakher Rahim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Cytokines ◽  
Systemic Inflammation ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Functional Impairments ◽  
Therapeutic Approaches ◽  
Novel Coronavirus ◽  
Pro Inflammatory Cytokines

Severe acute respiratory syndrome-coronavirus 2, a novel betacoronavirus, has caused the global outbreak of a contagious infection named coronavirus disease-2019. Severely ill subjects have shown higher levels of pro-inflammatory cytokines. Cytokine storm is the term that can be used for a systemic inflammation leading to the production of inflammatory cytokines and activation of immune cells. In coronavirus disease-2019 infection, a cytokine storm contributes to the mortality rate of the disease and can lead to multiple-organ dysfunction syndrome through auto-destructive responses of systemic inflammation. Direct effects of the severe acute respiratory syndrome associated with infection as well as hyperinflammatory reactions are in association with disease complications. Besides acute respiratory distress syndrome, functional impairments of the cardiovascular system, central nervous system, kidneys, liver, and several others can be mentioned as the possible consequences. In addition to the current therapeutic approaches for coronavirus disease-2019, which are mostly supportive, stem cell-based therapies have shown the capacity for controlling the inflammation and attenuating the cytokine storm. Therefore, after a brief review of novel coronavirus characteristics, this review aims to explain the effects of coronavirus disease-2019 cytokine storm on different organs of the human body. The roles of stem cell-based therapies on attenuating cytokine release syndrome are also stated.

scholarly journals May Medium Cut-Off Dialysis Membranes Have Impact on Outcome of COVID-19 Hemodialysis Patients?

2020 ◽  
Author(s):  
SERKAN FEYYAZ YALIN ◽  
AHMET MURT ◽  
MEVLUT TAMER DINCER ◽  
ERGUN PARMAKSIZ ◽  
SERAP YADIGAR ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Cytokines ◽  
Medical Records ◽  
Kidney Diseases ◽  
Hemodialysis Patients ◽  
Cytokine Storm ◽  
Radiologic Findings ◽  
Middle Molecules ◽  
Cytokine Levels ◽  
Dialysis Membranes

Abstract Purpose: Severe acute respiratory syndrome coronavirus 2 which is a novel type of coronavirus, may lead to high levels of expression of inflammatory cytokines. Medium cut-off membranes may make greater clearances for large-middle molecules (including cytokines) than low flux membranes. In this study, we aimed to evaluate impact of type of hemodialysis membranes on outcome of COVID 19+ hemodialysis patients.Methods: Forty nine COVID 19 + hemodialysis patients were included into study. The patients were categorized into two groups regarding type of hemodialysis membranes. Clinical data, etiologies of kidney diseases, comorbidities, laboratory and radiologic findings, antiviral, anti-cytokine treatments, and hemodialysis data were taken from medical records. Results: Medium cut-off membranes were used in 15 patients and low flux membranes were used in 34 patients. There were significantly more patients with comorbidities in medium cut-off group compare to low flux group (p=0,014). CRP and ferritin which are each surragates of cytokine storm in COVID-19, were significantly higher in medium cut-off membrane group compare to low flux group (p=0,00, 0,01, respectively).Conclusion: It may be an option to use medium cut-off membranes in hemodialysis patients with COVID 19 in order to reduce cytokine levels and prevent cytokine storm.

scholarly journals The Roles of Neutrophils in Cytokine Storms

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2318
Author(s):  
Lily Chan ◽  
Negar Karimi ◽  
Solmaz Morovati ◽  
Kasra Alizadeh ◽  
Julia E. Kakish ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
Neutrophilic Inflammation ◽  
Inflammatory Conditions ◽  
Cytokine Responses ◽  
Mediators Of Inflammation ◽  
Clinical Scenarios ◽  
Severe Infections ◽  
Destructive Potential

A cytokine storm is an abnormal discharge of soluble mediators following an inappropriate inflammatory response that leads to immunopathological events. Cytokine storms can occur after severe infections as well as in non-infectious situations where inflammatory cytokine responses are initiated, then exaggerated, but fail to return to homeostasis. Neutrophils, macrophages, mast cells, and natural killer cells are among the innate leukocytes that contribute to the pathogenesis of cytokine storms. Neutrophils participate as mediators of inflammation and have roles in promoting homeostatic conditions following pathological inflammation. This review highlights the advances in understanding the mechanisms governing neutrophilic inflammation against viral and bacterial pathogens, in cancers, and in autoimmune diseases, and how neutrophils could influence the development of cytokine storm syndromes. Evidence for the destructive potential of neutrophils in their capacity to contribute to the onset of cytokine storm syndromes is presented across a multitude of clinical scenarios. Further, a variety of potential therapeutic strategies that target neutrophils are discussed in the context of suppressing multiple inflammatory conditions.

scholarly journals Agents to reduce cytokine storm

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2909 ◽  
Author(s):  
Herwig Gerlach
Keyword(s):  
Septic Shock ◽  
Clinical Trials ◽  
Host Response ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
Clinical Investigations ◽  
Life Threatening ◽  
Sepsis And Septic Shock ◽  
Insight Into

The increasing insight into pathomechanisms of dysregulated host response in several inflammatory diseases led to the implementation of the term “cytokine storm” in the literature more than 20 years ago. Direct toxic effects as well as indirect immunomodulatory mechanisms during cytokine storm have been described and were the basis for the rationale to use several substances and devices in life-threatening infections and hyperinflammatory states. Clinical trials have been performed, most of them in the form of minor, investigator-initiated protocols; major clinical trials focused mostly on sepsis and septic shock. The following review tries to summarize the background, pathophysiology, and results of clinical investigations that had implications for the development of therapeutic strategies and international guidelines for the management of hyperinflammation during syndromes of cytokine storm in adult patients, predominantly in septic shock.

scholarly journals Cytokine Storm Syndrome in Covid-19 Patients: Characteristics and Diagnosis

2021 ◽  
pp. 1-3
Author(s):  
Rim M Harfouch ◽  
Keyword(s):  
Critical Illness ◽  
Severe Acute Respiratory Syndrome ◽  
Multiple Organ Failure ◽  
Inflammatory Cytokines ◽  
Critical Condition ◽  
Multiple Organ ◽  
Haemodynamic Instability ◽  
Cytokine Storm ◽  
Cytokine Activation ◽  
Global Pandemic

Cytokine storm syndrome (CSS) is a critical condition induced by a cascade of cytokine activation, characterized by overwhelming systemic inflammation, hyperferritinaemia, haemodynamic instability and multiple organ failure. At the end of 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly developed into a global pandemic. There is a dramatic increase of inflammatory cytokines in patients with COVID-19, suggesting the existence of cytokine storm in some critical illness patients. Here, we summarize the p

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
Coronary Artery ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Culture Media ◽  
Cytokine Secretion ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

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