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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a wide spectrum of symptom severity, which is manifested at different phases of infection and demands different levels of care. Viral load, host innate-immune response to SARS-CoV-2, and comorbidities have a direct impact on the clinical outcomes of COVID-19 patients and determine the diverse disease trajectories. The initial SARS-CoV-2 penetrance and replication in the host causes death of infected cells, determining the viral response. SARS-CoV-2 replication in the host triggers the activation of host antiviral immune mechanisms, determining the inflammatory response. While a healthy immune response is essential to eliminate infected cells and prevent spread of the virus, a dysfunctional immune response can result in a cytokine storm and hyperinflammation, contributing to disease progression. Current therapies for COVID-19 target the virus and/or the host immune system and may be complicated in their efficacy by comorbidities. Here we review the evidence for use of two classes of anti-inflammatory drugs, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of COVID-19. We consider the clinical evidence regarding the timing and efficacy of their use, their potential limitations, current recommendations and the prospect of future studies by these and related therapies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction : The coronavirus disease 2019 (COVID-19) pandemic, caused by a newly discovered coronavirus (severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2), continues to spread all around the world. Despite the emergency of COVID-19 worldwide, remdesivir is the only treatment that has been recently approved to treat the diseases, and other effective therapies are still lacking. SARS-CoV-2 may cause severe illness in 20% of patients. Based on available data, there is an association between interleukin-6 (IL-6) and severe COVID-19. Sarilumab is a fully human immunoglobulin G1 monoclonal antibody binding to both membrane-bound and soluble IL-6 receptors with high affinity and has been considered for off-label use in the treatment of COVID-19. Areas covered : The present article reviews recently published literature focusing on the pathophysiology of COVID-19 induced cytokine storm, the potential therapeutic role, and important clinical issues of sarilumab in the treatment of COVID-19 patients. Expert opinion : The off-label treatment administration is unavoidable in the critical situation of the COVID-19 pandemic. Further efforts should be directed to determine mechanisms of SARS-CoV-2 induced immune dysregulation as well as indications of sarilumab in the patients with COVID-19 to minimize concerns regarding its off-label administration.

Although many potent drugs have been used for cytokine storm, mortality is high for patients with coronavirus disease-2019 (COVID-19), which is followed up in the intensive care unit. Interferons (IFNs) are the major cytokines of the antiviral defense system released from many cell types. However, IFN-γ plays a key role in both primary and secondary cytokine storms. If the cytokine storm is not treated urgently, it will be fatal; therefore, it should be treated immediately. Anakinra, an interleukin-1 (IL-1) antagonist, tocilizumab, an IL-6 antagonist, and Janus kinase (JAK) inhibitors are successfully used in cytokine storm caused by COVID-19. However, sometimes, despite these treatments, the patient's clinical course does not improve. Emapalumab (Eb) is the human immunoglobulin G1 monoclonal antibody and is a potent and noncompetitive antagonist of IFN-γ. Eb can be life saving for cytokine storm caused by COVID-19, which is resistant to anakinra, tocilizumab, and JAK inhibitors., Competing Interests: None

Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the functions of the immune cells and alters the gene expression profile of different cytokines in response to various pathogenic stimuli, while many proinflammatory factors have been known to induce NF-κB signalling cascade. Besides, NF-κB has been known to potentiate the production of reactive oxygen species (ROS) leading to apoptosis in various tissues in many diseases and viral infections. Though the reports on the involvement of the NF-κB signalling pathway in COVID-19 are limited, the therapeutic benefits of NF-κB inhibitors including dexamethasone, a synthetic form of glucocorticoid, have increasingly been realized. Considering the fact, the abnormal activation of the NF-κB resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might be associated with the pathogenic profile of immune cells, cytokine storm and multiorgan defects. Thus, the pharmacological inactivation of the NF-κB signalling pathway can strongly represent a potential therapeutic target to treat the symptomatology of COVID-19. This article signifies pharmacological blockade of the phosphorylation of inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ), a key downstream effector of NF-κB signalling, for a therapeutic consideration to attenuate COVID-19.

The new coronavirus infection (Covid-19) is a pandemic that has affected the whole world and progresses with high morbidity and mortality. It has a high contagion rate and a course capable of rapid lung involvement with severe acute respiratory distress syndrome (ARDS) and pulmonary insufficiency. A severe clinical picture develops as a result of a "perfect cytokine storm" which results from possible immunological mechanisms triggered by the viral infection. Immune system dysregulation and possible autoinflammatory and autoimmune mechanisms are responsible for a higher amount of cytokines release from immune cells. Although no clear treatment of Covid-19 infection has emerged yet, it is argued that some disease-modifying anti-rheumatic drugs (DMARDs) may be effective in addition to anti-viral treatments. These drugs (anti-malarial drugs, colchicum dispert, biologics) have been well known to rheumatologists for years because they are used in the treatment of many inflammatory rheumatologic diseases. Another important issue is whether DMARDs, which can cause severe immunosuppression, pose a risk for Covid-19 infection and whether they have been discontinued beforehand. Although there are insufficient data on this subject, considering the risk of disease reactivation, patients may continue their DMARDs treatment under the supervision of a rheumatologist. In this article, the possible immunological mechanisms in the pathogenesis of Covid-19 infection and the efficacy and safety of various DMARDs used in the treatment are discussed from a rheumatologist's perspective in the light of recent literature data., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19.

Introduction: A novel coronavirus pneumonia (COVID-19) has caused significant life loss and healthcare burden globally. COVID-19 is known to cause a cytokine release syndrome (CRS) like response, and interleukin-6 (IL-6) is one of the cytokines involved. Clinicians are using IL-6 inhibitors to CRS, and researchers are investigating the use of IL-6 inhibitors, namely tocilizumab, sarilumab, siltuximab, in COVID-19 management., Areas Covered: In this article, we will discuss the pharmacology of these three inhibitors and summarize available clinical data via literature search on PubMed with keywords of tocilizumab, sarilumab, siltuximab, and COVID-19. While awaiting more data from randomized clinical trials on these drugs, observational studies and clinical reports have demonstrated IL-6 inhibitors showed some benefits in improving clinical outcome and a well-tolerated safety profile., Expert Opinion: There is a role for suppressing the immune response with IL-6 inhibitors that will continue to require investigation. These agents are available and have demonstrated a mild safety profile. There may be advantages to a targeted approach to suppressing the hyperinflammatory state of the disease. Timing, the long-term effects, and what cocktail of medications demonstrates the strongest outcomes are all important considerations as IL-6 inhibitors continue to be evaluated in this global pandemic.