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 Novel Coronavirus Disease 2019 (COVID-19) and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology

2021 ◽  
Vol 10 (4) ◽  
pp. 801
Author(s):  
Shumpei Yokota ◽  
Takako Miyamae ◽  
Yoshiyuki Kuroiwa ◽  
Kusuki Nishioka
Keyword(s):  
Immune System ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Disseminated Intravascular Coagulation ◽  
Inflammatory Responses ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Novel Coronavirus

The Novel Coronavirus Disease 2019 (COVID-19) has swept the world and caused a global pandemic. SARS-CoV-2 seems to have originated from bats as their reservoir hosts over time. Similar to SARS-CoV, this new virus also exerts its action on the human angiotensin-converting enzyme 2. This action causes infections in cells and establishes an infectious disease, COVID-19. Against this viral invasion, the human body starts to activate the innate immune system in producing and releasing proinflammatory cytokines such as IL-6, IL-1β, IL-8, TNF-α, and other chemokines, such as G-CSF, IP10 and MCPl, which all develop and increase the inflammatory response. In cases of COVID-19, excessive inflammatory responses occur, and exaggerated proinflammatory cytokines and chemokines are detected in the serum, resulting in cytokine release syndrome or cytokine storm. This causes coagulation abnormalities, excessive oxidation developments, mitochondrial permeability transition, vital organ damage, immune system failure and eventually progresses to disseminated intravascular coagulation and multiple organ failure. Additionally, the excessive inflammatory responses also cause mitochondrial dysfunction due to progressive and persistent stress. This damages cells and mitochondria, leaving products containing mitochondrial DNA and cell debris involved in the excessive chronic inflammation as damage-associated molecular patterns. Thus, the respiratory infection progressively leads to disseminated intravascular coagulation from acute respiratory distress syndrome, including vascular endothelial cell damage and coagulation-fibrinolysis system disorders. This condition causes central nervous system disorders, renal failure, liver failure and, finally, multiple organ failure. Regarding treatment for COVID-19, the following are progressive and multiple steps for mitigating the excessive inflammatory response and subsequent cytokine storm in patients. First, administering of favipiravir to suppress SARS-CoV-2 and nafamostat to inhibit ACE2 function should be considered. Second, anti-rheumatic drugs (monoclonal antibodies), which act on the leading cytokines (IL-1β, IL-6) and/or cytokine receptors such as tocilizumab, should be administered as well. Finally, melatonin may also have supportive effects for cytokine release syndrome, resulting in mitochondrial function improvement. This paper will further explore these subjects with reports mostly from China and Europe.

scholarly journals The Microbiota/Host Immune System Interaction in the Nose to Protect from COVID-19

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 345
Author(s):  
Arianna Di Stadio ◽  
Claudio Costantini ◽  
Giorgia Renga ◽  
Marilena Pariano ◽  
Giampietro Ricci ◽  
...  
Keyword(s):  
Immune System ◽  
Viral Entry ◽  
Upper Airway ◽  
Organ Damage ◽  
Host Immune System ◽  
Upper Airways ◽  
Mucosal Homeostasis ◽  
Resistance To Infection ◽  
Variable Clinical Presentation

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by variable clinical presentation that ranges from asymptomatic to fatal multi-organ damage. The site of entry and the response of the host to the infection affect the outcomes. The role of the upper airways and the nasal barrier in the prevention of infection is increasingly being recognized. Besides the epithelial lining and the local immune system, the upper airways harbor a community of microorganisms, or microbiota, that takes an active part in mucosal homeostasis and in resistance to infection. However, the role of the upper airway microbiota in COVID-19 is not yet completely understood and likely goes beyond protection from viral entry to include the regulation of the immune response to the infection. Herein, we discuss the hypothesis that restoring endogenous barriers and anti-inflammatory pathways that are defective in COVID-19 patients might represent a valid strategy to reduce infectivity and ameliorate clinical symptomatology.

scholarly journals COVID-19 and Cytokine Storm

2020 ◽  
Author(s):  
Mustafa Kurtuluş ◽  
İbrahim Pirim
Keyword(s):  
Immune Response ◽  
Host Response ◽  
Distress Syndrome ◽  
Multiple Organ ◽  
Past Century ◽  
Viral Agent ◽  
Disease Course ◽  
Cytokine Storm ◽  
The Past ◽  
Novel Coronavirus

Although the etiopathogenesis of infections has been largely illuminated by technical and scientific developments in the past century; many issues are still not clear today. The word “there is no disease, there is a patient” is stil valid today. Because the immune response of the host is as important as the virulence of the pathogen in infections and disease course can vary a lot according to the person. Cytokine Storm is seen exactly in a group of diseases where the host response is very prominent. For this reason, Cytokine Storm Syndrome (CSS) is mostly mentioned. CSS emerging due to different inflammatory etiologies; it is an overwhelming systemic inflammation, hemodynamic imbalance, multiple organ failure, and potentially leading to death. After being first seen in Influenza in 2003 as a viral agent, CSS was seen in SARS-Cov, MERS-CoV and SARS-CoV2, which were found to be the las thuman disease from the Corona viridea family.The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. Uncontrolled production of pro-inflammatory mediators contributes to, acut respiratory distress syndrome (ARDS) and cytokine storm syndrome in COVID-19.

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 Human Cell Receptors and Downstream Cascades: A Review of Molecular Aspects and Potential Therapeutic Targets against COVID-19

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Shervin Afzali ◽  
Mohammadvala AshtarNakhaei ◽  
Sara Shiari ◽  
Afshan Shirkavand ◽  
Shirin Farivar
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Immune System ◽  
Respiratory Distress Syndrome ◽  
Viral Entry ◽  
Distress Syndrome ◽  
Therapeutic Targets ◽  
System Response ◽  
Cytokine Storm ◽  
Cell Receptors ◽  
Immune System Response

Context: There have been two coronavirus-related pandemics during the past 18 years, including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV in 2002 and 2012, respectively. Seven years after the emergence of MERS, a new coronavirus (i.e., SARS-CoV-2) was detected in several patients in 2019. SARS-CoV-2 spread widely, and its high prevalence enabled the virus to start a new pandemic in 2020. It is believed that the higher infectivity of the virus in comparison to that of SARS-CoV is related to its molecular interaction affinity of transmembrane spike glycoprotein and human angiotensin-converting enzyme 2 (ACE-2) cell receptors. Moreover, the primary reason for the high case fatality rate (CFR) is the cytokine storm and acute respiratory distress syndrome (ARDS) because of the immune system response to the invaders. Hence, a solid understanding of the components involved in the mechanism of viral entry and immune system response is crucial for finding approaches to disrupt the virus interplay and neutralizing its impacts on the host immune system. In this review, we investigated the molecular aspect and potential therapeutic targets associated with cell receptors and downstream signaling cascades. Evidence Acquisition: In this review, we presented the available information regarding the coronavirus disease 2019 (COVID-19). A systematic search was implemented on several online databases, including Google Scholar, PubMed, and Scopus during 2019-2021 using the following keywords: "SARS-CoV-2", "COVID-19", "ACE-2", "Therapeutic Targets", "Acute respiratory distress syndrome", and "Cytokine Storm". Results: Various internal or external agents are responsible for the virus infectivity and stimulating acute immune system response. Since currently there is no cure for the treatment of COVID-19, several repurposed drugs can be employed to disrupt the process of viral entry and mitigate the symptoms raised by the cytokine storm. Inhibition of several agents, including signal transduction mediators and TMPRSS2 may be momentous. Conclusions: Despite the increase in the CFR, no drugs were developed with significant efficacy. Understanding the virus entry mechanism and the immune system’s role could help us surmount the problems in developing a promising drug or employing the repurposed ones.

Immune and Inflammatory Responses to Stroke: Good Or Bad?

2008 ◽  
Vol 3 (4) ◽  
pp. 254-265 ◽  
Author(s):  
P. A. McCombe ◽  
S. J. Read
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Therapeutic Option ◽  
Regulatory Lymphocytes ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Inflammatory and immune responses play important roles following ischaemic stroke. Inflammatory responses contribute to damage and also contribute to repair. Injury to tissue triggers an immune response. This is initiated through activation of the innate immune system. In stroke there is microglial activation. This is followed by an influx of lymphocytes and macrophages into the brain, triggered by production of pro-inflammatory cytokines. This inflammatory response contributes to further tissue injury. There is also a systemic immune response to stroke, and there is a degree of immunosuppression that may contribute to the stroke patient's risk of infection. This immunosuppressive response may also be protective, with regulatory lymphocytes producing cytokines and growth factors that are neuroprotective. The specific targets of the immune response after stroke are not known, and the details of the immune and inflammatory responses are only partly understood. The role of inflammation and immune responses after stroke is twofold. The immune system may contribute to damage after stroke, but may also contribute to repair processes. The possibility that some of the immune response after stroke may be neuroprotective is exciting and suggests that deliberate enhancement of these responses may be a therapeutic option.

Leptin ameliorates burn-induced multiple organ damage and modulates postburn immune response in rats

2005 ◽  
Vol 125 (1-3) ◽  
pp. 135-144 ◽  
Author(s):  
Barış Çakır ◽  
Hülya Çevik ◽  
Gazi Contuk ◽  
Feriha Ercan ◽  
Emel Ekşioğlu-Demiralp ◽  
...  
Keyword(s):  
Immune Response ◽  
Organ Damage ◽  
Multiple Organ

scholarly journals Natural Immunomodulators Treat the Cytokine Storm in SARS-CoV-2

2021 ◽  
Author(s):  
Heba S Abbas ◽  
Mona M Abd-elhakeem ◽  
Rania M Abd El Galil ◽  
Omar A. Reyad ◽  
Heba A Mohamed ◽  
...  
Keyword(s):  
Immune System ◽  
Host Cell ◽  
Viral Entry ◽  
Water Extract ◽  
Cell Receptor ◽  
Cytokine Storm ◽  
Emerging Viruses ◽  
Human Immune System ◽  
The World ◽  
Human Immune

Recently, the world has been dealing with a destructive global pandemic COVID-19 infection, since 2020; there were millions of infections and hundreds of thousands of deaths worldwide. With sequencing generations of the virus, around 60 % are expected to become infected during the pandemic. Unfortunately, no drug or vaccine has been approved because no real evidence from clinical trials in treatment was reached. According to current thinking, SARS-COV-2 mortality is caused by a cytokine storm syndrome in patients with hyper-inflammatory conditions, resulting in acute respiratory distress and finally death. In this review, we discuss the various types of natural immune-modulatory agents and their role in the management of SARS-COV-2, and cytokine storm syndrome. For example, Polyphenols as natural products can block the binding of SARS-CoV-2 spike protein to host cell receptor ACE2, stop viral entry into the host cell and block viral RNA replication. Also, Saikosaponins (A, B2, C, and D), triterpene glycosides, which are isolated from medicinal plants exert antiviral action against HCoV-22E9, and Houttuynia cordata water extract has antiviral effects on SARS-CoV. Moreover, eucalyptus oil has promising potential for COVID-19 prevention and treatment. There is an urgent need for research to improve the function of the human immune system all over the world. As a result, actions for better understanding and improving the human immune system are critical steps toward mitigating risks and negative outcomes. These approaches will be strongly recommended for future emerging viruses and pathogens.

scholarly journals Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruirong Chen ◽  
Zhien Lan ◽  
Jujian Ye ◽  
Limin Pang ◽  
Yi Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Respiratory Distress Syndrome ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Distress Syndrome ◽  
The Novel ◽  
Cytokine Storm ◽  
Major Threat ◽  
Primary Determinant ◽  
Multi Organ Dysfunction Syndrome

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how cytokine storms promote the deterioration of COVID-19. Here, we outline the pathophysiological processes through which cytokine storms contribute to the deterioration of SARS-CoV-2 infection and describe the interaction between SARS-CoV-2 and the immune system, as well as the pathophysiology of immune response dysfunction that leads to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and coagulation impairment. Treatments based on inhibiting cytokine storm-induced deterioration and occurrence are also described.

scholarly journals Splenectomy is Associated with Altered Leukocyte Kinetics after Severe Trauma

2020 ◽  
Author(s):  
Michel Teuben ◽  
Arne Hollman ◽  
Taco J. Blokhuis ◽  
Roman Pfeifer ◽  
Roy Spijkerman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Peripheral Blood ◽  
Cellular Immune Response ◽  
Severe Trauma ◽  
Multiple Organ ◽  
Liver Trauma ◽  
Trauma Patients ◽  
Severely Injured ◽  
Cellular Immune

Abstract Background Inadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma.Methods All adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals.Results A total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 hours, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions. Conclusions This study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.

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