Storm at the Time of Corona: A Glimpse at the Current Understanding and Therapeutic Opportunities of the SARS-CoV-2 Cytokine Storm

2020 ◽  
Vol 26 ◽  
Author(s):  
Monireh Torabi-Rahvar ◽  
Nima Rezaei
Keyword(s):  
Clinical Trials ◽  
Distress Syndrome ◽  
Severe Disease ◽  
Immune Dysregulation ◽  
Cytokine Storm ◽  
Jak Inhibitors ◽  
Severe Phenotype ◽  
Inflammatory Monocytes ◽  
Viral Virulence ◽  
Pro Inflammatory Cytokines

: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to severe disease in some cases, leading to acute respiratory distress syndrome, multi-organ failure, and death. This severe phenotype seems to be associated with a cytokine storm and immune dysregulation. Increased pro-inflammatory cytokines and CD14+CD16+ inflammatory monocytes, lymphopenia, and decreased levels of regulatory T cells are some of the immunological features that are seen in patients with SARS-CoV-2. As the outcome of SARS-CoV-2 is influenced by both viral virulence and dysregulated inflammatory response, a combination therapy approach using antiviral drugs plus anti-inflammatory treatments, such as corticosteroids, monoclonal antibodies against the IL-6 and IL-1β pathways, and JAK inhibitors are under clinical trials

scholarly journals Countermeasures to Coronavirus Disease 2019: Are Immunomodulators Rational Treatment Options—A Critical Review of the Evidence

2020 ◽  
Vol 7 (7) ◽  
Author(s):  
Daniel B Chastain ◽  
Tia M Stitt ◽  
Phong T Ly ◽  
Andrés F Henao-Martínez ◽  
Carlos Franco-Paredes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Failure ◽  
Distress Syndrome ◽  
Treatment Options ◽  
Immune Dysregulation ◽  
Lung Damage ◽  
Safety And Efficacy ◽  
Rational Treatment ◽  
Immunomodulatory Therapies

Abstract Severe acute respiratory syndrome coronavirus 2 is associated with higher concentrations of proinflammatory cytokines that lead to lung damage, respiratory failure, and resultant increased mortality. Immunomodulatory therapy has the potential to inhibit cytokines and quell the immune dysregulation. Controversial data found improved oxygenation after treatment with tocilizumab, an interleukin-6 inhibitor, sparking a wave of interest and resultant clinical trials evaluating immunomodulatory therapies. The purpose of this article is to assess potential proinflammatory targets and review the safety and efficacy of immunomodulatory therapies in managing patients with acute respiratory distress syndrome associated with coronavirus disease 2019.

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 Immunomodulation and Regenerative Capacity of MSCs for Long-COVID

2021 ◽  
Vol 22 (22) ◽  
pp. 12421
Author(s):  
Xin Ya Loke ◽  
Siti A. M. Imran ◽  
Gee Jun Tye ◽  
Wan Safwani Wan Kamarul Zaman ◽  
Fazlina Nordin
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Distress Syndrome ◽  
Regenerative Therapy ◽  
Cytokine Storm ◽  
Regenerative Capacity ◽  
Lung Injuries ◽  
Severity Of The Disease ◽  
Effective Drugs ◽  
Future Utilization

The rapid mutation of the SARS-CoV-2 virus is now a major concern with no effective drugs and treatments. The severity of the disease is linked to the induction of a cytokine storm that promotes extensive inflammation in the lung, leading to many acute lung injuries, pulmonary edema, and eventually death. Mesenchymal stem cells (MSCs) might prove to be a treatment option as they have immunomodulation and regenerative properties. Clinical trials utilizing MSCs in treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) have provided a basis in treating post-COVID-19 patients. In this review, we discussed the effects of MSCs as an immunomodulator to reduce the severity and death in patients with COVID-19, including the usage of MSCs as an alternative regenerative therapy in post-COVID-19 patients. This review also includes the current clinical trials in utilizing MSCs and their potential future utilization for long-COVID treatments.

scholarly journals Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200160 ◽  
Author(s):  
Antonella Fara ◽  
Zan Mitrev ◽  
Rodney Alexander Rosalia ◽  
Bakri M. Assas
Keyword(s):  
Potential Role ◽  
Distress Syndrome ◽  
The Body ◽  
Type I ◽  
Cytokine Storm ◽  
Disease Prognosis ◽  
Cytokine Levels ◽  
Cellular Components ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Coronavirus disease 2019 (COVID-19) has swept the world, unlike any other pandemic in the last 50 years. Our understanding of the disease has evolved rapidly since the outbreak; disease prognosis is influenced mainly by multi-organ involvement. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure are strongly associated with morbidity and mortality. The COVID-19 disease pathology is plausibly linked to the hyperinflammatory response of the body characterized by pathological cytokine levels. The term ‘cytokine storm syndrome’ is perhaps one of the critical hallmarks of COVID-19 disease severity. In this review, we highlight prominent cytokine families and their potential role in COVID-19, the type I and II interferons, tumour necrosis factor and members of the Interleukin family. We address various changes in cellular components of the immune response corroborating with changes in cytokine levels while discussing cytokine sources and biological functions. Finally, we discuss in brief potential therapies attempting to modulate the cytokine storm.

scholarly journals Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in Covid-19 patients

2020 ◽  
Author(s):  
Irma Convertino ◽  
Marco Tuccori ◽  
Sara Ferraro ◽  
Giulia Valdiserra ◽  
Emiliano Cappello ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Healthcare Systems ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
Jak Inhibitors ◽  
Immunomodulating Drugs

Sars-CoV-2 complications include pneumonia and acute respiratory distress syndrome (ARDS), which requires intensive care unit admission. These conditions have rapidly overwhelmed healthcare systems, with detrimental effects on the quality of care and increased mortality. Social isolation strategies have been implemented worldwide with the aim of reducing hospital pressure. Among therapeutic strategies, the use of immunomodulating drugs, to improve prognosis, seems promising. Particularly, since pneumonia and ARDS are associated with a cytokine storm, drugs belonging to therapeutic classes as anti-IL-6, anti-TNF and JAK inhibitors, are currently studied. In this paper, we discuss the potential advantages of the most promising pharmacological approaches.

scholarly journals Potential therapeutic approaches for targeted inhibition of inflammatory cytokines following COVID-19 infection-induced cytokine storm

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nelli Morgulchik ◽  
Foteini Athanasopoulou ◽  
Edmund Chu ◽  
Yoriko Lam ◽  
Nazila Kamaly
Keyword(s):  
Inflammatory Cytokines ◽  
Distress Syndrome ◽  
Multiorgan Failure ◽  
Cytokine Storm ◽  
Therapeutic Approaches ◽  
Global Pandemic ◽  
Blood Clots ◽  
Specific Manner ◽  
Targeted Inhibition ◽  
Pro Inflammatory Cytokines

Coronavirus disease 2019 (COVID-19) is a deadly respiratory disease caused by severe acute respiratory syndrome coronavirus 2, which has caused a global pandemic since early 2020 and severely threatened people's livelihoods and health. Patients with pre-diagnosed conditions admitted to hospital often develop complications leading to mortality due to acute respiratory distress syndrome (ARDS) and associated multiorgan failure and blood clots. ARDS is associated with a cytokine storm. Cytokine storms arise due to elevated levels of circulating cytokines and are associated with infections. Targeting various pro-inflammatory cytokines in a specific manner can result in a potent therapeutic approach with minimal host collateral damage. Immunoregulatory therapies are now of interest in order to regulate the cytokine storm, and this review will summarize and discuss advances in targeted therapies against cytokine storms induced by COVID-19.

scholarly journals COVID-19-associated secondary hemophagocytic lymphohistiocytosis (cytokine storm syndrome)

2021 ◽  
Vol 76 (1) ◽  
pp. 51-66
Author(s):  
Ekaterina I. Alekseeva ◽  
Rustem F. Tepaev ◽  
Ilia Y. Shilkrot ◽  
Tatyana M. Dvoryakovskaya ◽  
Aleksander G. Surkov ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Distress Syndrome ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
C Reactive Protein ◽  
Routine Testing ◽  
Reactive Protein ◽  
Pathogenetic Therapy ◽  
Secondary Hemophagocytic Lymphohistiocytosis ◽  
Pro Inflammatory Cytokines

In most cases, COVID-19 has a favorable outcome. However, the risk of developing critical forms of the disease, including secondary hemophagocytic lymphohistiocytosis HLH (cytokine storm syndrome), remains high. This dictates the interest in studying pathogenetic mechanisms, features of the clinical picture, laboratory and instrumental criteria for covid-19 disease. The article analyzes the causes of acute respiratory distress syndrome and multiple organ failure as manifestations of HLH. The necessity of monitoring signs of hyperinflammation (ferritin, C-reactive protein, etc., biomarkers of inflammation) and activation of thrombosis is substantiated, in order to make timely decisions about the beginning of pathogenetic therapy. However, there are limitations for routine testing of the level of Pro-inflammatory cytokines. Information about the diagnostic criteria of HLH is summarized, and the expediency of these criteria for establishing secondary HLH, which has complicated the course of COVID-19, is emphasized.

THE ROLE OF DEXAMETHASONE DOSING IN THE TREATMENT OF COVID-19 AND ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS): A SYSTEMATIC REVIEW

2021 ◽  
pp. 21-26
Author(s):  
Ж.К. УТАРОВ ◽  
К.К. КУРАКБАЕ
Keyword(s):  
Systematic Review ◽  
Intensive Care Unit ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Distress Syndrome ◽  
Lung Ventilation ◽  
Cytokine Storm ◽  
Main Effect ◽  
The World

Новый тип коронавируса был обнаружен в декабре 2019 года в провинции Ухань Китайской Народной Республики и получил называние SARS-CoV-2, а болезнь назвался COVID-19. Болезнь проявляется многими клиническими симптомами (лихорадка, кашель, одышка, повторяющийся озноб, мышечные боли, головная боль, боль в горле, потеря обоняния (аносмия) и / или вкуса (агевзия) и диарея), но в основном повреждает верхние и нижние дыхательные пути. Поскольку COVID-19 в основном вызывает вирусное поражение легких, многие пациенты попадают в больницу в тяжелом состоянии с острым респираторным дистресссиндромом (ОРДС). Ухудшение состояния при вирусной пневмонии идёт быстрыми темпами, и у многих пациентов уже в течение нескольких часов развивается дыхательная недостаточность, требующая немедленной респираторной поддержки. Учитывая, что новый тип коронавируса пришел в нашу жизнь на десятилетия, уже сейчас необходимо рассмотреть новые направления лечения. В настоящее время рассматриваются различные варианты лечения с целью полного уничтожения вируса или прекращения его дальнейшего развития, в том числе препарат дексаметазон, принадлежащий к группе глюкокортикоидов, который продемонстрировал основную эффективность. На сегодняшний день проведено несколько рандомизированных клинических испытаний (РКИ) с применением дексаметазона, но оптимальная доза и продолжительность применения препарата до сих пор не определены. Currently, a lot of research is being conducted using various medicines to treat COVID-19 disease, which puts the world at a standstill. In particular, we are talking about the drug dexamethasone, which has the main effect on ensuring that patients are not transferred to the intensive care unit and are not connected to articial lung ventilation. Although several randomized clinical trials have been conducted, the dose of dexamethasone has not yet been rened to suppress or stop the cytokine storm.

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 Yellow fever disease severity is driven by an acute cytokine storm modulated by an interplay between the human gut microbiome and the metabolome

2021 ◽  
Author(s):  
Adam-Nicolas Pelletier ◽  
Mateus Tomazella ◽  
Karina de Carvalho ◽  
Andre Nicolau ◽  
Marianna Marmoratto ◽  
...  
Keyword(s):  
Disease Severity ◽  
Yellow Fever ◽  
Cytokine Production ◽  
Severe Disease ◽  
Cytokine Storm ◽  
Human Gut ◽  
Proteolytic Bacteria ◽  
Integrated Omics ◽  
Treg Differentiation ◽  
Pro Inflammatory Cytokines

AbstractInfection with Yellow Fever (YF) can lead to multiple outcomes ranging from death from total organ failure to clearance of viremia and survival. The mechanisms underlying these differences in clinical outcomes have yet to be defined. We had access to a cohort of YF infected subjects that showed these range of outcomes. An unbiased integrated OMICs approach was used to identify pathways and effector molecules that drive the severe disease and death as compared to resolution of infection. We used the MELD and SIC score as objective markers of disease severity. We show that a specific signature of upregulated innate pro-inflammatory cytokines significantly demarcates subjects with severe disease leading to death from subjects who clear virus. Pathogen sequencing showed heightened levels of proteolytic bacteria at the i.e Actinobacteria and these were correlated to lower levels of tryptophan and tyrosine amino acids measured by untargeted metabolomics. These two features were significantly associated to MELD scores synonymous of milder disease. Propionate a bacterial metabolite that triggers Treg differentiation that can as well limit the hyperimmune activation associated to severe outcome was also associated to improved outcome. Our results suggest a model whereby proteolytic bacteria limit the availability of the aromatic amino acid pool available for cytokine production thereby preventing the induction of the cytokine storm that is associated to severe disease and death.

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