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 Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1067
Author(s):  
Oleksandr Oliynyk ◽  
Wojciech Barg ◽  
Anna Slifirczyk ◽  
Yanina Oliynyk ◽  
Vitaliy Gurianov ◽  
...  
Keyword(s):  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
C Reactive Protein ◽  
Treatment Results ◽  
Reactive Protein ◽  
Median Serum ◽  
D Dimer

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, p < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p = 0.043), RR = 2.1 (95% CI 1.0–4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p = 0.013), RR = 0.50 (95% CI 0.25–0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.

IMMUNOPATHOLOGY AND IMMUNOPHARMACOTHERAPY OF CORONAVIRUS DISEASE 2019 (COVID-19): FOCUS ON INTERLEUKIN 6

2020 ◽  
Vol 58 (3) ◽  
pp. 245-261 ◽  
Author(s):  
E. L. Nasonov
Keyword(s):  
Interleukin 6 ◽  
Prognostic Value ◽  
Macrophage Activation ◽  
Critical Conditions ◽  
Malignant Neoplasms ◽  
Inflammatory Rheumatic Diseases ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Immune Mediated

The Coronavirus Disease 2019 (COVID-19) pandemic has drawn closer attention than ever before to the problems of the immunopathology of human diseases, many of which have been reflected when studying immune-mediated inflammatory rheumatic diseases (IIRDs). The hyperimmune response called a cytokine storm, the pathogenetic subtypes of which include hemophagocytic lymphohistiocytosis, macrophage activation syndrome, and cytokine release syndrome, is among the most serious complications of IIRDs or treatment for malignant neoplasms and may be a stage of COVID-19 progression. A premium is placed to interleukin-6 (IL-6) in the spectrum of cytokines involved in the pathogenesis of the cytokine storm syndrome. The clinical introduction of monoclonal antibodies (mAbs) that inhibit the activity of this cytokine (tocilizumab, sarilumab, etc.) is one of the major advances in the treatment of IIRDs and critical conditions within the cytokine storm syndrome in COVID-19. The review discusses data on the clinical and prognostic value of IL-6 and the effectiveness of anti-IL-6 receptor and anti-IL-6 mAbs, as well as prospects for personalized therapy of the cytokine storm syndrome in COVID-19.

scholarly journals Biomimetic Nanoparticles Potentiate the Anti-Inflammatory Properties of Dexamethasone and Reduce the Cytokine Storm Syndrome: An Additional Weapon against COVID-19?

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2301
Author(s):  
Roberto Molinaro ◽  
Anna Pasto ◽  
Francesca Taraballi ◽  
Federica Giordano ◽  
Jamil A. Azzi ◽  
...  
Keyword(s):  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Array Analysis ◽  
Pathological Conditions ◽  
Significant Survival Advantage ◽  
Significant Survival ◽  
Biomimetic Nanoparticles ◽  
Anti Inflammatory

Recent studies on coronavirus infectious disease 2019 (COVID-19) pathophysiology indicated the cytokine release syndrome induced by the virus as the main cause of mortality. Patients with severe COVID-19 infection present a systemic hyper inflammation that can lead to lung and multi-organ injuries. Among the most recent treatments, corticosteroids have been identified to be effective in mitigating these catastrophic effects. Our group has recently developed leukocyte-derived nanovesicles, termed leukosomes, able to target in vivo the inflamed vasculature associated with pathological conditions including cancer, cardiovascular diseases, and sepsis. Herein, to gain insights on the anti-inflammatory properties of leukosomes, we investigated their ability to reduce uncontrolled inflammation in a lethal model of lipopolysaccharide (LPS)-induced endotoxemia, recapitulating the cytokine storm syndrome observed in COVID-19 infection after encapsulating dexamethasone. Treated animals showed a significant survival advantage and an improved immune response resolution, as demonstrated by a cytokine array analysis of pro- and anti-inflammatory cytokines, chemokines, and other immune-relevant markers. Our results showed that leukosomes enhance the therapeutic activity of dexamethasone and better control the inflammatory response compared to the free drug. Such an approach could be useful for the development of personalized therapies in the treatment of hyperinflammation related to infectious diseases, including the ones caused by COVID-19.

scholarly journals Can Natural Polyphenols Help in Reducing Cytokine Storm in COVID-19 Patients?

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5888
Author(s):  
Giovanna Giovinazzo ◽  
Carmela Gerardi ◽  
Caterina Uberti-Foppa ◽  
Lucia Lopalco
Keyword(s):  
Poor Prognosis ◽  
Antioxidant Properties ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Natural Polyphenols ◽  
The World ◽  
Great Progress ◽  
Inflammatory Drugs ◽  
Bioactive Phytochemicals ◽  
Anti Inflammatory

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.

scholarly journals Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome.

2021 ◽  
Author(s):  
Oleksandr Oliynyk ◽  
Wojciech Barg ◽  
Anna Slifirczyk ◽  
Yanina Oliynyk ◽  
Vitaliy Gurianov ◽  
...  
Keyword(s):  
Group Treatment ◽  
Macrophage Activation ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
C Reactive Protein ◽  
Treatment Results ◽  
Reactive Protein ◽  
Median Serum ◽  
D Dimer

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In each group, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/ml, p &amp;lt;0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p=0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p=0.013), RR = 0.50 (95% CI 0.25-0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients it contributed to reduced mortality.

The Efficacy of Anti-inflammatory Agents in the Prevention of Atrial Fibrillation Recurrences

2020 ◽  
Vol 28 (1) ◽  
pp. 137-151
Author(s):  
Homa Nomani ◽  
Sara Saei ◽  
Thomas P. Johnston ◽  
Amirhossein Sahebkar ◽  
Amir Hooshang Mohammadpour
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Therapeutic Option ◽  
General Rule ◽  
Promising Candidate ◽  
Term Basis ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Meta Analyses ◽  
Af Recurrence

: Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF.

scholarly journals Clinical Outcomes of Aspirin Interaction with Other Non-Steroidal Anti-Inflammatory Drugs: A Systematic Review

2018 ◽  
Vol 21 (1s) ◽  
pp. 48s-73s ◽  
Author(s):  
Zuhair Alqahtani ◽  
Fakhreddin Jamali
Keyword(s):  
Clinical Trials ◽  
Platelet Aggregation ◽  
Clinical Outcomes ◽  
Randomized Clinical Trials ◽  
Ex Vivo ◽  
Biologically Active ◽  
Cardioprotective Effect ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Aggregation Level

Purpose: Concomitant use of some non-Aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) reduces the extent of platelet aggregation of Aspirin (acetylsalicylic acid). This is while many observational studies and clinical trials suggest that Aspirin reduces cardiovascular (CV) risk attributed to the use of NANSAIDs. Thus, the therapeutic outcome of the interaction needs to be assessed. Methods: We searched various databases up to October 2017 for molecular interaction studies between the drugs and long-term clinical outcomes based on randomized clinical trials and epidemiological observations that reported the effect estimates of CV risks (OR, RR or HR; 95% CI) of the interacting drugs alone or in combinations. Comparisons were made between outcomes after Aspirin alone, NANSAIDs alone and Aspirin with naproxen, ibuprofen, celecoxib, meloxicam, diclofenac or rofecoxib. Results: In total, 32 eligible studies (20 molecular interactions studies and 12 observational trials) were found. Conflicting in vitro/in vivo/ex vivo platelet aggregation data were found for ibuprofen, naproxen and celecoxib. Nevertheless, for naproxen, the interaction at the aggregation level did not amount to a loss of cardioprotective effects of Aspirin. Similarly, for ibuprofen, the results overwhelmingly suggest no negative clinical CV outcomes following the combination therapy. Meloxicam and rofecoxib neither interacted with Aspirin at the level of platelet aggregation nor altered clinical outcomes. The clinical outcomes data for celecoxib and diclofenac are in conflict. Conclusion: Aspirin appears to maintain its cardioprotective effect in the presence of naproxen, ibuprofen, meloxicam and rofecoxib. The limited available data suggest that the effect of interaction at the platelet aggregation level may dissipate shortly, or the reduced platelet aggregation yielded by the interaction may be sufficient for cardioprotection; i.e., no need for near complete aggregation. In addition, cardioprotective effect of Aspirin, despite reduced platelet aggregation caused by NANSAIDs, may be through its involvement in other mechanisms such as the renin-angiotensin system and/or metabolism of arachidonic acid to biologically active compounds mediated by cytochrome P450. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Potential of natural astaxanthin in alleviating the risk of cytokine storm and improve health in COVID-19: A scoping review

2020 ◽  
Author(s):  
Jayanta Talukdar ◽  
Bhaskar Bhadra ◽  
Santanu Dasgupta ◽  
Vinod Nagle
Keyword(s):  
Clinical Trials ◽  
Inflammatory Cytokines ◽  
Scoping Review ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Elevated Serum ◽  
Cytokine Release ◽  
Prisma Statement ◽  
Anti Oxidant ◽  
Anti Inflammatory

Abstract Background: Natural astaxanthin as a potent anti-oxidant and broad-spectrum anti-inflammatory bioactive molecule plays important role in modulating the immune response, speculated to be a potential supplement to alleviate cytokine release storm in COVID-19. Objective: Review of published literature to summarize the rationale for possible benefits of natural astaxanthin to support COVID-19 patients. Methods: Retrieved relevant literature from electronic databases including Google scholar, PubMed, Scopus, etc. and reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We adapted the article as scoping review. Results: Cytokine release syndrome (CRS) is reported as a common feature in COVID-19, which can lead to potentially fatal, hyper-inflammatory acute respiratory distress condition, diagnosed with elevated serum level of pro-inflammatory cytokines like IL-6, CRP, etc. that positively correlated with disease severity. Anti-inflammatory drug, like tocilizumab, etc. are under clinical trials as anti-CRS therapy. Astaxanthin can potentially alleviate CRS by regulating inflammatory cytokines by inhibiting the activities of NF-kB, TNF-α, JAK/STAT-3, etc. Available pre-clinical and clinical trials data support its excellent safety, and potential therapeutic and health benefits. Conclusions: Natural astaxanthin has tremendous potential as co-adjunctive supplement, desiring necessary clinical supports on its efficacy and beneficial against COVID-19.

Sign in / Sign up

Export Citation Format

Share Document