scholarly journals Severe COVID-19: what have we learned with the immunopathogenesis?

2020 ◽  
Vol 60 (1) ◽  
Author(s):  
Bruno Bordallo ◽  
Mozart Bellas ◽  
Arthur Fernandes Cortez ◽  
Matheus Vieira ◽  
Marcelo Pinheiro
Keyword(s):  
Immune Response ◽  
Clinical Evidence ◽  
Randomized Clinical Trials ◽  
Immune Dysregulation ◽  
Therapeutic Strategies ◽  
Interferon Response ◽  
Cytokine Storm ◽  
Disease Pathogenesis ◽  
Lung Tissue Damage ◽  
Diffuse Lung

Abstract The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself. Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena. Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.

scholarly journals Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Franck Mauvais-Jarvis ◽  
Sabra L Klein ◽  
Ellis R Levin
Keyword(s):  
Immune Response ◽  
Distress Syndrome ◽  
Immune Dysregulation ◽  
Innate Immune ◽  
The Novel ◽  
Cytokine Storm ◽  
Inflammatory Infiltration ◽  
Biological Sex ◽  
17Β Estradiol ◽  
Novel Coronavirus

Abstract Severe outcomes and death from the novel coronavirus disease 2019 (COVID-19) appear to be characterized by an exaggerated immune response with hypercytokinemia leading to inflammatory infiltration of the lungs and acute respiratory distress syndrome. Risk of severe COVID-19 outcomes is consistently lower in women than men worldwide, suggesting that female biological sex is instrumental in protection. This mini-review discusses the immunomodulatory and anti-inflammatory actions of high physiological concentrations of the steroids 17β-estradiol (E2) and progesterone (P4). We review how E2 and P4 favor a state of decreased innate immune inflammatory response while enhancing immune tolerance and antibody production. We discuss how the combination of E2 and P4 may improve the immune dysregulation that leads to the COVID-19 cytokine storm. It is intended to stimulate novel consideration of the biological forces that are protective in women compared to men, and to therapeutically harness these factors to mitigate COVID-19 morbidity and mortality.

scholarly journals Androgens and cardiac diseases

2013 ◽  
Vol 80 (4) ◽  
Author(s):  
Vittorio Bianchi ◽  
Alessandro Mezzani
Keyword(s):  
Cardiovascular System ◽  
Sex Steroids ◽  
Vascular Remodeling ◽  
Clinical Evidence ◽  
Randomized Clinical Trials ◽  
Large Body ◽  
Therapeutic Strategies ◽  
Plasma Testosterone ◽  
Testosterone Therapy ◽  
Novel Therapeutic Strategies

Although androgens have been considered deleterious for the cardiovascular system, recent data have demonstrated favourable testosterone effects on cardiac and vascular remodeling and clinical outcome. However, the cardiovascular risk-benefit profile of testosterone therapy remains largely elusive due to lack of well-designed and adequately powered randomized clinical trials. In any case, a large body of clinical evidence underlines that low plasma testosterone levels should be considered a risk factor for cardiovascular disease, and that the evaluation of sex steroids should be included in the routine clinical evaluation of cardiac patients. A better understanding of the mechanism regulating the effects of testosterone on cardiovascular system could lead to novel therapeutic strategies in several cardiac patient populations, such as chronic heart failure patients and those who recently underwent cardiac surgery.

scholarly journals NSAIDs/Nitazoxanide/Azithromycin Repurposed for COVID-19: Potential Mitigation of the Cytokine Storm Interleukin-6 Amplifier via Immunomodulatory Effects

2021 ◽  
Author(s):  
Mina Kelleni
Keyword(s):  
Interleukin 6 ◽  
Randomized Clinical Trials ◽  
Inflammatory Responses ◽  
Real Life ◽  
Interferon Response ◽  
Rational Approach ◽  
Cytokine Storm ◽  
Immunomodulatory Effects ◽  
Double Blind ◽  
Anti Inflammatory

Introduction Mediators of immunity and inflammation are playing a crucial role in COVID-19 pathogenesis and complications as demonstrated by several genetic and clinical studies. Moreover, a weak, irregular, or inhibited early interferon response to SARS CoV-2 infection was shown to trigger an exaggerated inflammatory response leading to the COVID-19 associated mortality. Thus, repurposing of drugs that possess anti-inflammatory and/or immune-modulatory effects for COVID-19 is considered a rational approach. Areas covered We present a concise analysis and interpretations of selected studies that correlated COVID-19 with dysregulated interferon and inflammatory responses while reflecting on our academic and real-life experience using non-steroidal anti-inflammatory drugs, nitazoxanide and azithromycin for management of COVID-19. Moreover, we interpret the recent results that suggested a potential survival benefit of low dose aspirin and colchicine when used for COVID-19. Expert opinion Nitazoxanide/azithromycin combination has been first hypothesized by the author and practiced by him and several researchers to benefit COVID-19 patients due to a potential ability to augment the natural interferon response as well as their positive immunomodulatory effects on several cytokines. Furthermore, NSAIDs, that were unfortunately almost globally avoided early in the COVID-19 era and still avoided in many developing ones or at best of second choice in the developed ones, have been early postulated and clinically practiced by the author to prevent or ameliorate COVID-19 complications and mortality due to their ability to prevent, constrain or reverse COVID-19 associated dysregulated immune and hyper-inflammatory responses through mitigating the formation of several inflammatory cytokines and pathways including the interleukin-6 amplifier and its NF-kB component, as well as modulation of a described monocytic immunological dysrhythmia, which is also known to trigger the COVID-19 cytokine storm. Finally, we repeat our previous call to adopt our observational study that used these drugs in sufficiently powered double blind randomized clinical trials as COVID-19 potential safe and economic cure might be available and unfortunately repeatedly ignored for one year.

scholarly journals Triggers, Timescales, and Treatments for Cytokine-Mediated Tissue Damage

2020 ◽  
Author(s):  
David McBride ◽  
Matthew Kerr ◽  
Nicholas Dorn ◽  
Dora Ogbonna ◽  
Evan Santos ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Cytokine Production ◽  
Viral Infections ◽  
Immune Dysregulation ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
T Cell Therapy ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Successes And Challenges

Inflammation, an essential cytokine-mediated process for generating a neutralising immune response against pathogens, is generally protective. However, aberrant or excessive production of proinflammatory cytokines is associated with uncontrolled local and systemic inflammation, resulting in cell death and often irreversible tissue damage. Uncontrolled inflammation can manifest over timescales spanning hours to years and is primarily dependent on the triggering event. Rapid and potentially lethal increases in cytokine production, or ‘cytokine storm’, develops in hours to days, and is associated with cancer cell-based immunotherapies, such as chimeric antigen receptor T-cell therapy. On the other hand, some bacterial and viral infections with high microbial replication or highly potent antigens elicit immune responses that result in supraphysiological systemic cytokine concentrations, which manifest over days to weeks. Immune dysregulation in autoimmune diseases can lead to chronic cytokine-mediated tissue damage spanning months to years, which often occurs episodically. Upregulation of IL-1, IL-6, IFN-γ, TNF, and granulocyte macrophage colony-stimulating factor frequently coincides with cytokine storm, sepsis, and autoimmune disease. Inhibition of proinflammatory molecules via antagonist monoclonal antibodies has improved clinical outcomes, but the complexity of the underlying immune dysregulation results in high variability. Rather than a ‘one size fits all’ treatment approach, an identification of disease endotypes may permit the development of effective therapeutic strategies that address the contributors of disease progression. Here, the authors present a literature review of the cytokine-associated aetiology of acute and chronic cytokine-mediated tissue damage, describe successes and challenges in developing clinical treatments, and highlight advancements in preclinical therapeutic strategies for mitigating pathological cytokine production.

scholarly journals Interleukin-17A (IL-17A): the silent amplifier of COVID-19

2021 ◽  
Author(s):  
Francesco Maione ◽  
Gian Casillo ◽  
Federica Raucci ◽  
Mariarosaria Bucci
Keyword(s):  
Immune Response ◽  
Disease Progression ◽  
Clinical Outcomes ◽  
Disease Severity ◽  
Systemic Inflammation ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
Interleukin 17A ◽  
Potential Link ◽  
Per Se

One of the hallmarks of COVID-19 is the cytokine storm that provokes primarily pneumonia followed by systemic inflammation. Emerging evidence has identified a potential link between elevated levels of interleukin-17A (IL-17A) and disease severity and progression. Considering that per se IL-17A can activate several inflammatory pathways, it is plausible to hypothesize an involvement of this cytokine in COVID-19 clinical outcomes. Thus, this cytokine can represent a marker of disease progression and/or a target to develop therapeutic strategies. This hypothesis paper aims to propose this “unique” cytokine as a silent amplifier of the COVID-19 immune response and (potentially) related therapy.

Is Immune Response Relevant in Interstitial Lung Disease?

2020 ◽  
Vol 16 (1) ◽  
pp. 18-27
Author(s):  
Manzoor M. Khan
Keyword(s):  
Immune Response ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Fibrosis ◽  
Lymphocytic Infiltration ◽  
Therapeutic Strategies ◽  
Mediators Of Inflammation ◽  
Acquired Immune Responses ◽  
Novel Therapeutic Strategies

Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.

scholarly journals Macrophage Activation and Cytokine Release Syndrome in COVID-19: Current Updates and Analysis of Repurposed and Investigational Anti-Cytokine Drugs

Drug Research ◽  
2021 ◽  
Author(s):  
Ashif Iqubal ◽  
Farazul Hoda ◽  
Abul Kalam Najmi ◽  
Syed Ehtaishamul Haque
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Macrophage Activation ◽  
Fatality Rate ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Disease Condition ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

AbstractCoronavirus disease (COVID-19) emerged from Wuhan, has now become pandemic and the mortality rate is growing exponentially. Clinical complication and fatality rate is much higher for patients having co-morbid issues. Compromised immune response and hyper inflammation is hall mark of pathogenesis and major cause of mortality. Cytokine release syndrome (CRS) or cytokine storm is a term used to affiliate the situation of hyper inflammation and therefore use of anti-cytokine and anti-inflammatory drugs is used to take care of this situation. Looking into the clinical benefit of these anti-inflammatory drugs, many of them enter into clinical trials. However, understanding the immunopathology of COVID-19 is important otherwise, indiscriminate use of these drugs could be fetal as there exists a very fine line of difference between viral clearing cytokines and inflammatory cytokines. If any drug suppresses the viral clearing cytokines, it will worsen the situation and hence, the use of these drugs must be based on the clinical condition, viral load, co-existing disease condition and severity of the infection.

scholarly journals COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 993
Author(s):  
Renuka Raman ◽  
Krishna J. Patel ◽  
Kishu Ranjan
Keyword(s):  
Immune Response ◽  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Small Molecules ◽  
Viral Vector ◽  
Therapeutic Strategies ◽  
Convincing Evidence ◽  
Plasma Therapy ◽  
Therapeutic Monoclonal Antibodies ◽  
Increased Susceptibility

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

scholarly journals Still’s Disease in the Constellation of Hyperinflammatory Syndromes: A Link with Kawasaki Disease?

2021 ◽  
Vol 10 (15) ◽  
pp. 3244
Author(s):  
Perrine Dusser ◽  
Isabelle Koné-Paut
Keyword(s):  
Immune Response ◽  
Kawasaki Disease ◽  
Innate Immune Response ◽  
Adaptive Response ◽  
Genetic Factors ◽  
Innate Immune ◽  
Cytokine Storm ◽  
Still’S Disease ◽  
Still's Disease ◽  
Excessive Activation

Still’s disease and Kawasaki disease (KD) today belong to the group of cytokine storm syndromes, a pathophysiological set related to excessive activation of the innate immune response. We present here a personal vision of what can link these two diseases, taking up their concepts at their beginning. By their many clinical and physiopathological similarities, we conclude that they constitute a common spectrum whose fate is modified by subtle differences in terms of adaptive response that could, in part, be driven by genetic factors.

Obesity and diabetes: lipids, ‘nowhere to run to'

2008 ◽  
Vol 116 (2) ◽  
pp. 113-123 ◽  
Author(s):  
Margaret J. Hill ◽  
David Metcalfe ◽  
Philip G. McTernan
Keyword(s):  
Short Review ◽  
Therapeutic Strategies ◽  
Cellular Systems ◽  
Ectopic Fat ◽  
Central Adiposity ◽  
Disease Pathogenesis ◽  
Fat Accumulation ◽  
Obesity And Diabetes

Although specific pathogenic entities contributing to diabetic risk, such as central adiposity, ectopic fat accumulation, hyperlipidaemia and inflammation, are well-characterized, the response of cellular systems to such insults are less well understood. This short review highlights the effect of increasing fat mass on ectopic fat accumulation, the role of triacylglycerols (triglycerides) in Type 2 diabetes mellitus and cardiovascular disease pathogenesis, and selected current therapeutic strategies used to ameliorate these risk factors.

Sign in / Sign up

Export Citation Format

Share Document