scholarly journals Suppression of miR-155 attenuates lung cytokine storm induced by SARS-CoV-2 infection in human ACE2-transgenic mice

2020 ◽  
Author(s):  
Dharmendra Kumar Soni ◽  
Juan Cabrera-Luque ◽  
Swagata Kar ◽  
Chaitali Sen ◽  
Joseph Devaney ◽  
...  
Keyword(s):  
Viral Entry ◽  
Inflammatory Responses ◽  
Viral Disease ◽  
High Rate ◽  
Cytokine Storm ◽  
Novel Therapy ◽  
Antiviral Responses ◽  
Cellular Defense ◽  
Angiotensin I Converting Enzyme ◽  
Global Pandemic

ABSTRACTCoronavirus disease 2019 (COVID-19) is a recent global pandemic. It is a deadly human viral disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a high rate of infection, morbidity and mortality. Therefore, there is a great urgency to develop new therapies to control, treat and prevent this disease. Endogenous microRNAs (miRNAs, miRs) of the viral host are key molecules in preventing viral entry and replication, and building an antiviral cellular defense. Here, we have analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of SARS-CoV-2 infection. Subsequently, we have analyzed the potency of anti-miR-155 therapy in a COVID-19 mouse model (mice transgenic for human angiotensin I-converting enzyme 2 receptor (tg-mice hACE2)). We report for the first time that miR-155 expression is elevated in COVID-19 patients. Further, our data indicate that the viral load as well as miR-155 levels are higher in male relative to female patients. Moreover, we find that the delivery of anti-miR-155 to SARS-CoV-2-infected tg-mice hACE2 effectively suppresses miR-155 expression, and leads to improved survival and clinical scores. Importantly, anti-miR-155-treated tg-mice hACE2 infected with SARS-CoV-2 not only exhibit reduced levels of pro-inflammatory cytokines, but also have increased anti-viral and anti-inflammatory cytokine responses in the lungs. Thus, our study suggests anti-miR-155 as a novel therapy for mitigating the lung cytokine storm induced by SARS-CoV-2 infection.

scholarly journals Triangle of cytokine storm, central nervous system involvement, and viral infection in COVID-19: the role of sFasL and neuropilin-1

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kiarash Saleki ◽  
Mohammad Banazadeh ◽  
Niloufar Sadat Miri ◽  
Abbas Azadmehr
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Viral Entry ◽  
Fas Ligand ◽  
Inflammatory Responses ◽  
Central Nervous System Involvement ◽  
Cytokine Storm ◽  
Cns Injury ◽  
Fas Receptor ◽  
Neuropilin 1

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is identified as the cause of coronavirus disease 2019 (COVID-19), and is often linked to extreme inflammatory responses by over activation of neutrophil extracellular traps (NETs), cytokine storm, and sepsis. These are robust causes for multi-organ damage. In particular, potential routes of SARS-CoV2 entry, such as angiotensin-converting enzyme 2 (ACE2), have been linked to central nervous system (CNS) involvement. CNS has been recognized as one of the most susceptible compartments to cytokine storm, which can be affected by neuropilin-1 (NRP-1). ACE2 is widely-recognized as a SARS-CoV2 entry pathway; However, NRP-1 has been recently introduced as a novel path of viral entry. Apoptosis of cells invaded by this virus involves Fas receptor–Fas ligand (FasL) signaling; moreover, Fas receptor may function as a controller of inflammation. Furthermore, NRP-1 may influence FasL and modulate cytokine profile. The neuroimmunological insult by SARS-CoV2 infection may be inhibited by therapeutic approaches targeting soluble Fas ligand (sFasL), cytokine storm elements, or related viral entry pathways. In the current review, we explain pivotal players behind the activation of cytokine storm that are associated with vast CNS injury. We also hypothesize that sFasL may affect neuroinflammatory processes and trigger the cytokine storm in COVID-19.

scholarly journals 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 ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 565
Author(s):  
Ali A. Rabaan ◽  
Shamsah H. Al-Ahmed ◽  
Mohammed A. Garout ◽  
Ayman M. Al-Qaaneh ◽  
Anupam A Sule ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Viral Entry ◽  
Inflammatory Responses ◽  
Organ Damage ◽  
Multiple Organ ◽  
Special Focus ◽  
Cytokine Storm ◽  
Damage Recognition ◽  
Gender And Age

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

scholarly journals SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB

2020 ◽  
Author(s):  
Christopher J. Neufeldt ◽  
Berati Cerikan ◽  
Mirko Cortese ◽  
Jamie Frankish ◽  
Ji-Young Lee ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Significant Proportion ◽  
Lung Damage ◽  
Systemic Complications ◽  
Mild Disease ◽  
Antiviral Responses ◽  
Global Pandemic

AbstractSARS-CoV-2 is a novel virus that has rapidly spread, causing a global pandemic. In the majority of infected patients, SARS-CoV-2 leads to mild disease; however, in a significant proportion of infections, individuals develop severe symptoms that can lead to permanent lung damage or death. These severe cases are often associated with high levels of pro-inflammatory cytokines and low antiviral responses which can lead to systemic complications. We have evaluated transcriptional and cytokine secretion profiles from infected cell cultures and detected a distinct upregulation of inflammatory cytokines that parallels samples taken from infected patients. Building on these observations, we found a specific activation of NF-κB and a block of IRF3 nuclear translocation in SARS-CoV-2 infected cells. This NF-κB response is mediated by cGAS-STING activation and could be attenuated through STING targeting drugs. Our results show that SARS-CoV-2 curates a cGAS-STING mediated NF-κB driven inflammatory immune response in epithelial cells that likely contributes to inflammatory responses seen in patients and might be a target to suppress severe disease symptoms.

scholarly journals SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Christopher J. Neufeldt ◽  
Berati Cerikan ◽  
Mirko Cortese ◽  
Jamie Frankish ◽  
Ji-Young Lee ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Significant Proportion ◽  
Lung Damage ◽  
Systemic Complications ◽  
Mild Disease ◽  
Antiviral Responses ◽  
Global Pandemic

AbstractSARS-CoV-2 is a novel virus that has rapidly spread, causing a global pandemic. In the majority of infected patients, SARS-CoV-2 leads to mild disease; however, in a significant proportion of infections, individuals develop severe symptoms that can lead to long-lasting lung damage or death. These severe cases are often associated with high levels of pro-inflammatory cytokines and low antiviral responses, which can cause systemic complications. Here, we have evaluated transcriptional and cytokine secretion profiles and detected a distinct upregulation of inflammatory cytokines in infected cell cultures and samples taken from infected patients. Building on these observations, we found a specific activation of NF-κB and a block of IRF3 nuclear translocation in SARS-CoV-2 infected cells. This NF-κB response was mediated by cGAS-STING activation and could be attenuated through several STING-targeting drugs. Our results show that SARS-CoV-2 directs a cGAS-STING mediated, NF-κB-driven inflammatory immune response in human epithelial cells that likely contributes to inflammatory responses seen in patients and could be therapeutically targeted to suppress severe disease symptoms.

scholarly journals Modeling the dynamics of within-host viral infection and evolution predicts quasispecies distributions and phase boundaries separating distinct classes of infections

2021 ◽  
Author(s):  
Greyson R Lewis ◽  
Wallace F Marshall ◽  
Barbara A Jones
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Viral Infections ◽  
Viral Disease ◽  
Significant Inhibition ◽  
High Rate ◽  
Variable Binding ◽  
Wide Range ◽  
Viral Responses ◽  
Physical Phenomena

We use computational modeling to study within-host viral infection and evolution. In our model, viruses exhibit variable binding to cells, with better infection and replication countered by a stronger immune response and a high rate of mutation. By varying host conditions (permissivity to viral entry T and immune clearance intensity A) for large numbers of cells and viruses, we study the dynamics of how viral populations evolve from initial infection to steady state and obtain a phase diagram of the range of cell and viral responses. We find three distinct replicative strategies corresponding to three physiological classes of viral infections: acute, chronic, and opportunistic. We show similarities between our findings and the behavior of real viral infections such as common flu, hepatitis, and SARS-CoV-2019. The phases associated with the three strategies are separated by a phase transition of primarily first order, in addition to a crossover region. Our simulations also reveal a wide range of physical phenomena, including metastable states, periodicity, and glassy dynamics. Lastly, our results suggest that the resolution of acute viral disease in patients whose immunity cannot be boosted can only be achieved by significant inhibition of viral infection and replication.

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.

scholarly journals Obesity as a Risk Factor for Severe COVID-19 and Complications: A Review

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 933
Author(s):  
Fien Demeulemeester ◽  
Karin de Punder ◽  
Marloes van Heijningen ◽  
Femke van Doesburg
Keyword(s):  
Risk Factor ◽  
Disease Severity ◽  
Viral Entry ◽  
Thrombus Formation ◽  
Clinical Findings ◽  
High Risk Group ◽  
Therapeutic Interventions ◽  
Cytokine Storm ◽  
Negative Consequences ◽  
Major Complications

Emerging data suggest that obesity is a major risk factor for the progression of major complications such as acute respiratory distress syndrome (ARDS), cytokine storm and coagulopathy in COVID-19. Understanding the mechanisms underlying the link between obesity and disease severity as a result of SARS-CoV-2 infection is crucial for the development of new therapeutic interventions and preventive measures in this high-risk group. We propose that multiple features of obesity contribute to the prevalence of severe COVID-19 and complications. First, viral entry can be facilitated by the upregulation of viral entry receptors, like angiotensin-converting enzyme 2 (ACE2), among others. Second, obesity-induced chronic inflammation and disruptions of insulin and leptin signaling can result in impaired viral clearance and a disproportionate or hyper-inflammatory response, which together with elevated ferritin levels can be a direct cause for ARDS and cytokine storm. Third, the negative consequences of obesity on blood coagulation can contribute to the progression of thrombus formation and hemorrhage. In this review we first summarize clinical findings on the relationship between obesity and COVID-19 disease severity and then further discuss potential mechanisms that could explain the risk for major complications in patients suffering from obesity.

Hemocytometric characteristics of COVID-19 patients with and without cytokine Storm syndrome on the Sysmex XN-10 hematology analyzer

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Remy J. H. Martens ◽  
Arjan J. van Adrichem ◽  
Nadine J. A. Mattheij ◽  
Calvin G. Brouwer ◽  
Daan J. L. van Twist ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Cytokine Storm ◽  
Forward Scatter ◽  
Global Pandemic ◽  
Hematology Analyzer ◽  
Blood Neutrophils ◽  
Fatal Form ◽  
High Fluorescence ◽  
The Moment ◽  
Respiratory Complaints

AbstractObjectivesCOVID-19 is an ongoing global pandemic. There is an urgent need for identification and understanding of clinical and laboratory parameters related to progression towards a severe and fatal form of this illness, often preceded by a so-called cytokine-storm syndrome (CSS). Therefore, we explored the hemocytometric characteristics of COVID-19 patients in relation to the deteriorating clinical condition CSS, using the Sysmex XN-10 hematology analyzer.MethodsFrom March 1st till May 16th, 2020, all patients admitted to our hospital with respiratory complaints and suspected for COVID-19 were included (n=1,140 of whom n=533 COVID-19 positive). The hemocytometric parameters of immunocompetent cells in peripheral blood (neutrophils [NE], lymphocytes [LY] and monocytes [MO]) obtained upon admission to the emergency department (ED) of COVID-19 positive patients were compared with those of the COVID-19 negative ones. Moreover, patients with CSS (n=169) were compared with COVID-19 positive patients without CSS, as well as with COVID-19 negative ones.ResultsIn addition to a significant reduction in leukocytes, thrombocytes and absolute neutrophils, it appeared that lymphocytes-forward scatter (LY-FSC), and reactive lymphocytes (RE-LYMPHO)/leukocytes were higher in COVID-19-positive than negative patients. At the moment of presentation, COVID-19 positive patients with CSS had different neutrophils-side fluorescence (NE-SFL), neutrophils-forward scatter (NE-FSC), LY-FSC, RE-LYMPHO/lymphocytes, antibody-synthesizing (AS)-LYMPHOs, high fluorescence lymphocytes (HFLC), MO-SSC, MO-SFL, and Reactive (RE)-MONOs. Finally, absolute eosinophils, basophils, lymphocytes, monocytes and MO-FSC were lower in patients with CSS.ConclusionsHemocytometric parameters indicative of changes in immunocompetent peripheral blood cells and measured at admission to the ED were associated with COVID-19 with and without CSS.

scholarly journals A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

2021 ◽  
Vol 22 (3) ◽  
pp. 1118
Author(s):  
Abdulaziz Alamri ◽  
Derek Fisk ◽  
Deepak Upreti ◽  
Sam K. P. Kung
Keyword(s):  
Dendritic Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Immune Responses ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Viral Disease ◽  
Cell Recruitment ◽  
Cross Presentation ◽  
Cell Immunity ◽  
Immune Cell Recruitment

Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

UPDATE ON CARDIOVASCULAR IMPLICATIONS OF COVID 19

2021 ◽  
pp. 238-242
Author(s):  
Pradeep Kumar Radhakrishnan ◽  
Gayathri Ananyajyothi Ambat ◽  
Roshini Ambat ◽  
Syed Ilas Basha ◽  
Hema Prakash ◽  
...  
Keyword(s):  
Virus Disease ◽  
Systemic Vasculitis ◽  
Myocardial Damage ◽  
Viral Disease ◽  
Cardiac Damage ◽  
Corona Virus ◽  
Global Pandemic ◽  
Acute Myocardial Injury ◽  
Exercise Induced

On March 11 2020 WHO declares corona viral disease as a global pandemic .COVID 19 pandemic has taken the world by storm and many countries like India is now experiencing a second surge due to mutant strains. Global health emergency has been precipitated by this corona virus disease caused by SARS CoV2.Acute and intermediate effects on cardiovascular system are becoming obvious with progression of time. SARS-CoV-2-related endothelial dysfunction results in an augmented risk for venous thromboembolism, systemic vasculitis, endothelial cell apoptosis, and inammation in various organs. Acute infections have troponin elevation more due to indirect cardiac damage though denite patterns of direct damage do exist. Intermediate evaluation in patients with resolved infections shows increased incidence of exercise induced arrhythmias and residual cardiovascular symptoms. The virus with its zoonotic origin based upon its genomic identity to bat derived SARS corona virus has a human to human transmission mode.ACE 2 receptors facilitate cellular entry and has been implicated in direct and indirect myocardial damage. Myocarditis, acute myocardial injury, arrhythmias and thromboembolism dominates the clinical picture. Role of imaging must be dened in relation to relevant clinical ndings. With arrival of vaccine and widespread vaccination global programs, we can look forward to understanding and managing long term complications of this disease. Prognostic implications of a resolved disease need to be evaluated by future studies.

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