scholarly journals Can Ivermectin be Useful for COVID-19 Management as an Immunomodulating Agent?

2020 ◽  
Vol 12 (1) ◽  
pp. 7-8
Author(s):  
Sergey Sheleg
Keyword(s):  
Cytokine Storm ◽  
Life Threatening

The possibility of using ivermectin in the treatment of COVID-19 as an immunomodulating agent, has been discussed, which may prevent life-threatening virally driven cytokine storm syndrome.

scholarly journals Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence

2021 ◽  
Vol 22 (6) ◽  
pp. 3059
Author(s):  
Corrado Pelaia ◽  
Cecilia Calabrese ◽  
Eugenio Garofalo ◽  
Andrea Bruni ◽  
Alessandro Vatrella ◽  
...  
Keyword(s):  
Review Article ◽  
Lung Damage ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Cytokine Storm ◽  
Future Perspectives ◽  
Pathogenic Role ◽  
Refractory Rheumatoid Arthritis ◽  
Life Threatening

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

scholarly journals A promising therapy of tocilizumab and helmet CPAP to prevent intubation for COVID-19 induced severe ARDS: a case report

2020 ◽  
Vol 24 (6) ◽  
Author(s):  
Septian Adi Permana ◽  
Adhrie Sugiarto ◽  
Muhammad Husni Thamrin ◽  
Arifin . ◽  
Harsini .
Keyword(s):  
Diabetes Mellitus ◽  
Case Report ◽  
Laboratory Tests ◽  
Leukocyte Count ◽  
Cytokine Storm ◽  
Rt Pcr ◽  
Life Threatening ◽  
Cost Efficient ◽  
The Cost ◽  
Easy Operation

A 59 yrs old male with severe ARDS due to COVID-19 infection was in life threatening ‘cytokine storm’. He had also co-morbids including diabetes mellitus and hypertension. He had come from Grobogan, a red area for COVID-19. Clinical finding indicted systemic inflammatory response syndrome (SIRS) with dyspnea, tachycardia, and high fever. Laboratory tests showed raised leukocyte count, CRP, SGOT/SGPT, blood sugar, PCT, low PaO2/FiO2 ratio. RT PCR showed he was infected by COVID-19. Sputum culture showed Klebsiella infection and CXR showed bilateral pneumonia. Patient was treated with standard therapy and a combination of tocilizumab for cytokine-storm and helmet CPAP for severe ARDS. Helmet CPAP has become the first modality for COVID-19 ARDS in some countries but not in Indonesia. We chose helmet CPAP because of the cost efficient, comfortable, and easy operation compared to other modality. We chose tocilizumab because it uses a single dose. Although it is expensive, only one dose is enough and it is effective in blocking the cytokine storm. We found that helmet CPAP and tocilizumab combination in COVID-19 lead severe ARDS could be promising to prevent intubation for patients. Key words: Helmet CPAP; ARDS; COVID-19; Tocilizumab; Cytokine storm Citation: Permana SA, Sugiarto A, Thamrin MH, Arifin, Harsini. A promising therapy of tocilizumab and helmet CPAP to prevent intubation for COVID-19 induced severe ARDS: a case report. Anaesth. pain intensive care 2020;24(6):659-663; DOI: 10.35975/apic.v24i6.1409 Received - 17 September 2020, Reviewed – 01 October 2020, Accepted – 6 November 2020

scholarly journals Natural phytochemicals, Phenformin, and Docosahexaenoic acid (DHA) as a Novel Inhibitors of IL-6 and ACE2 receptors, a Therapeutic Strategy for targeting COVID-19 Cell Entry and Cytokine Storm. An insilico Approach

2021 ◽  
Author(s):  
Amr kamel khalil Ahmed ◽  
Mahmoud Elkazzaz
Keyword(s):  
Docosahexaenoic Acid ◽  
Binding Affinity ◽  
Active Sites ◽  
Epigallocatechin Gallate ◽  
Cell Entry ◽  
Binding Affinities ◽  
Cytokine Storm ◽  
High Binding ◽  
Life Threatening ◽  
High Binding Affinity

Abstract Cytokine storm syndrome (CSS) is a life-threatening consequence of inflammatory immunological illnesses; it can also occur with COVID-19 infection. CSS is characterized by a disruption in cytokine synthesis, including regulatory, pro-inflammatory and anti-inflammatory cytokines, resulting in pathologic stimulation of innate in addition to adaptive (Th17 and Th1 mediated) response. In the pathophysiology of CSS, interleukin-6 could play a key role. The significant role of IL-6 in COVID-19 pathogenesis was established in a wide variety of researches, which reported that the plasma concentration of IL-6 was raised in COVID-19 patients with severe symptoms. COVID-19 spike protein binding to angiotensin-converting enzyme 2 (ACE2), the virus's cellular receptor, causes a cascade of molecular processes that could result in hyperinflammation which may lead to cytokine storm. Therefore, the development of new natural therapies and repurposing some drugs such as Phenformin and Docosahexaenoic acid that could compete with COVID-19 for ACE2 binding or inhibit IL-6 activity may possibly help COVID-19 patients avoid a cytokine storm and save their lives through inhibiting IL-6 and preventing SARS-CoV-2 RBD attachment to ACE2. Herein we made a docking based screening for some natural phytochemicals and drugs that could be repurposed according to our findings to counter COVID-19 cell entry and inhibit the hyper activation of IL-6. Our results revealed that a five phytochemicals including Epigallocatechin gallate (EGCG), bromelain, luteolin, vitexin and isovitexin) showed a high binding affinities with best interactions with the active sites of IL-6. The binding affinities of these phytochemicals including, EGCG, bromelain, luteolin, vitexin and isovitexin with IL-6 were (-7.7, -6.7, -7.4, -7.2 and − 7.3 ), respectively. In addition to, phenformin showed a high binding affinity with best interactions with the active sites of IL-6 and ACE2. The binding affinity of phenformin with IL-6 was (-7.4) and with ACE 2 ( -7.2). Docosahexaenoic acid (DHA) had a moderate binding affinity and moderate interactions with the active sites of IL-6 and had a high binding affinity with best interactions with ACE2 active sites. The binding affinity of Docosahexaenoic acid(DHA) with IL-6 was (-5.3) and with AC2 (-6.3).ConclusionProposing possible IL-6 inhibitors with less adverse effects has been suggested as a way to aid COVID-19 patients who are suffering from severe cytokine storms. This study has been designed to elucidate the potential of potent antiviral phytocompounds as well as phenformin and Docosahexaenoic acid (DHA) as a potent ACE2 and IL-6 inhibitors. The compounds interact with different active sites of IL6 and ACE2 which are involved in direct or indirect contacts with the ACE2 and IL-6 receptors which might act as potential blockers of functional ACE2 and IL-6 receptor complex. It worth mentioning that phenformin which showed high binding affinity with both ACE2 and IL-6 is currently under investigation for treating COVID-19 ClinicalTrials.gov Identifier: NCT05003492

Continuous Renal Replacement Therapy with oXiris® Membrane in Severe Ebstein-Barr Virus-Mediated Hemophagocytic Lymphohistiocytosis: A Case Report

2020 ◽  
pp. 1-4
Author(s):  
Karla N. Samman ◽  
Hussein Baalbaki ◽  
Josée Bouchard ◽  
Martin Albert
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Inflammatory Markers ◽  
Blood Purification ◽  
Cytokine Storm ◽  
Barr Virus ◽  
Ebstein Barr Virus ◽  
Life Threatening

Hemophagocytic lymphohistiocytosis (HLH), a life-threatening disease with uncontrolled immune activation and inflammatory reaction, often leads to a deadly cytokine storm. In severe Ebstein-Barr virus-triggered HLH receiving standard immunosuppression, continuous renal replacement therapy (CRRT) with oXiris<sup>®</sup> blood purification membrane resulted in a timely reduction of inflammatory markers and discontinuation of vasopressors. To our knowledge, this is the first report of successful use of the oXiris<sup>®</sup> membrane in HLH.

scholarly journals A zebrafish model of COVID-19-associated cytokine storm syndrome reveals differential proinflammatory activities of Spike proteins of SARS-CoV-2 variants of concern.

2021 ◽  
Author(s):  
Sylwia D Tyrkalska ◽  
Alicia Martinez-Lopez ◽  
Ana B Arroyo ◽  
Francisco J Martinez-Morcillo ◽  
Sergio Candel ◽  
...  
Keyword(s):  
Cytokine Storm ◽  
Zebrafish Model ◽  
Angiotensin Converting Enzyme 2 ◽  
Life Threatening ◽  
Proinflammatory Activity ◽  
Proinflammatory Role ◽  
Emergency Myelopoiesis ◽  
Short Time ◽  
Protein Variants

The sudden and unexpected appearance of the COVID-19 pandemic turned the whole world upside down in a very short time. One of the main challenges faced has been to understand COVID-19 patient heterogeneity, as a minority develop life-threatening hyperinflammation, the so-called cytokine storm syndrome (CSS). Using the unique advantages of the zebrafish model we report here the proinflammatory role of Spike (S) proteins from different SARS-CoV-2 variants of concern after injection into the hindbrain ventricle, a cavity filled with cerebrospinal fluid to which immune cells can be easily recruited and that mimics the alveolar environment of the human lung. We found that wild type/Wuhan variant S1 (S1WT) protein promoted neutrophil and macrophage recruitment, local and systemic hyperinflammation, emergency myelopoiesis, and hemorrhages. In addition, S1γ protein was more proinflammatory and S1δ was less proinflammatory than S1WT and, strikingly, Sβ promoted delayed and long-lasting inflammation. Pharmacological inhibition of the canonical inflammasome robustly alleviated S1 protein-induced inflammation and emergency myelopoiesis. In contrast, genetic inhibition of angiotensin-converting enzyme 2 strengthened the proinflammatory activity of S1, and the administration of angiopoietin (1-7) fully rescued S1-induced hyperinflammation and hemorrhages. These results shed light into the mechanisms orchestrating the COVID-19-associated CSS and the host immune response to different SARS-CoV-2 S protein variants.

scholarly journals Mitigate the cytokine storm due to the severe COVID-19: A computational investigation of possible allosteric inhibitory actions on IL-6R and IL-1R using selected phytochemicals

2020 ◽  
Vol 11 (4) ◽  
pp. 351-363
Author(s):  
Harindu Rajapaksha ◽  
Bingun Tharusha Perera ◽  
Jeewani Meepage ◽  
Ruwan Tharanga Perera ◽  
Chithramala Dissanayake
Keyword(s):  
Conformational Changes ◽  
Oral Bioavailability ◽  
Interleukin 1 ◽  
Extensive Literature ◽  
The Novel ◽  
Cytokine Storm ◽  
Allosteric Sites ◽  
Life Threatening ◽  
Effective Drugs

The novel corona virus 2019 (COVID 19) is growing at an increasing rate with high mortality. Meanwhile, the cytokine storm is the most dangerous and potentially life-threatening event related to COVID 19. Phyto-compounds found in existing Ayurveda drugs have the ability to inhibit the Interleukin 6 (IL-6R) and Interleukin 1 (IL-1R) receptors. IL-6R and IL-1R receptors involve in cytokine storm and recognition of phytochemicals with proven safety profiles could open a pathway to the development of the most effective drugs against cytokine storm. In this study, we intend to perform an in silico investigation of effective phyto compounds, which can be isolated from selected medicinal herbs to avoid cytokine storm, inhibiting the IL-6 and IL-1 receptor binding process. An extensive literature survey followed by virtual screening was carried out to identify phytochemicals with potential anti-hyper-inflammatory action. Flexible docking was conducted for validated models of IL-1R and IL-6R-α with the most promising phytochemicals at possible allosteric sites using AutoDock Vina. Molecular dynamics (MD) studies were conducted for selected protein-ligand complexes using LARMD server and conformational changes were evaluated. According to the results, taepeenin J had Gibbs energy (ΔG) of -10.85 kcal/mol towards IL-1R but had limited oral bioavailability. MD analysis revealed that taepeenin J can cause significant conformational movements in IL-1R. Nortaepeenin B showed a ΔG of -8.5 kcal/mol towards IL-6R-α with an excellent oral bioavailability. MD analysis predicted that it can cause significant conformational movements in IL-6R-α. Hence, the evaluated phytochemicals are potential candidates for further in vitro studies for the development of medicine against cytokine storm on behalf of SARS-COV-2 infected patients.

scholarly journals Covid 19 & vertical transmission

2021 ◽  
Vol 2 (2) ◽  
pp. 278-283
Author(s):  
Kanad Dev Nayar ◽  
Shweta Gupta ◽  
Sabina Sanan ◽  
Preeti Mehra ◽  
Jaya Mishra ◽  
...  
Keyword(s):  
Public Health ◽  
Acute Respiratory Distress Syndrome ◽  
Vertical Transmission ◽  
Distress Syndrome ◽  
Case Fatality ◽  
Public Health Emergency ◽  
Cytokine Storm ◽  
Vulnerable Group ◽  
Increased Risk ◽  
Life Threatening

The current coronavirus pandemic is a serious public health emergency and has led to widespread damage globally. Although there are many coronaviruses, the particular that is responsible for this pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).It has incubation period of around 2 to 7 days and most symptomatic patients can have fever, malaise, cough, or loss of taste or smell, with some cases developing into life threatening pneumonia and acute respiratory distress syndrome with case fatality rates range from 1% to 2%. Pregnancy is considered as a vulnerable group for any infection and knowledge regarding the possible risk of vertical transmission of this virus is very limited but is important for counseling regarding COVID-19 related pregnancy risks and for further management. COVID 19 infection in mothers basically leads to hypoxia, inflammatory response & cytokine storm. It appears around 10% of SARS- Cov-2 infected pregnant women require hospitalization with respiratory support    COVID-19 can infect the placenta as confirmed by the presence of SARSCoV- 2 viral RNA in the placenta and evidence of virions found within the syncytiotrophoblast. The possible neonatal outcomes are increased risk of

scholarly journals Lung-targeted Macrophage Biomimetic Nanocarriers Based on Platycodon Grandiflorum Polysaccharides for Calming Cytokine Storm in Pneumonia

2021 ◽  
Author(s):  
Yi Li ◽  
Chunjing Guo ◽  
Qiang Chen ◽  
Yanguo Su ◽  
Huimin Guo ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Severe Pneumonia ◽  
Scientific Basis ◽  
Cytokine Storm ◽  
Platycodon Grandiflorum ◽  
Life Threatening ◽  
Targeting Ability ◽  
Delivery Efficiency

Abstract Background Pneumonia is a life-threatening respiratory disease without effective treatment due to uncontrolled inflammation of the lung tissue. Suppression of cytokine storms may be one of the keys to saving the lives of patients with severe pneumonia. Given the fragile delivery efficiency of drugs in vivo, novel delivery platforms to address these issues are necessary. Results Here, we developed a biomimetic nanocarrier (MNPs) with macrophage membranes coated ROS-responsive Platycodon grandiflorum polysaccharides nanoparticles (PNPs) for targeted delivery of curcumin (MNPs@Cur) to inflamed lungs and treat inflammation by calming cytokine storms. In the study, we could clearly find that MNPs@Cur significantly attenuated inflammation and cytokine storm syndrome in acute lung injury (ALI) mice by neutralizing multiple proinfammatory cytokines. Interestingly, we found that the PNPs also had potent pulmonary targeting compared to other polysaccharide carriers, which probably means that PNPs have inherited the natural targeting ability in the medicinal guide theory of Traditional Chinese Medicine (TCM). Conclusion The results demonstrated that the developed drug delivery system may serve as an effective and safe nanoplatform for the treatment of pneumonia, as well as provide experimental scientific basis for the medicinal guide theory of TCM and its clinical application.

scholarly journals Natural phytochemicals, Phenformin, and Docosahexaenoic acid (DHA) as a Novel Inhibitors of IL-6 and ACE2 receptors, a Therapeutic Strategy for targeting COVID-19 Cell Entry and Cytokine Storm. An insilico Approach

2021 ◽  
Author(s):  
Amr Kamel Khalil Ahmed ◽  
Mahmoud Elkazzaz
Keyword(s):  
Docosahexaenoic Acid ◽  
Binding Affinity ◽  
Active Sites ◽  
Epigallocatechin Gallate ◽  
Cell Entry ◽  
Binding Affinities ◽  
Cytokine Storm ◽  
High Binding ◽  
Life Threatening ◽  
High Binding Affinity

Cytokine storm syndrome (CSS) is a life-threatening consequence of inflammatory immunological illnesses; it can also occur with COVID-19 infection . CSS is characterized by a disruption in cytokine synthesis, including regulatory , pro-inflammatory andanti-inflammatory cytokines, resulting in pathologic stimulation of innate in addition to adaptive (Th17and Th1mediated) response. In the pathophysiology of CSS, interleukin-6 could play a key role. The significant role of IL-6 in COVID-19pathogenesis was established in a wide variety of researches , which reported that the plasma concentration of IL-6was raised in COVID-19 patients with severe symptoms .COVID-19 spike protein binding to angiotensin-converting enzyme 2 (ACE2), the virus's cellular receptor, causes a cascade of molecular processes that could result in hyperinflammation which may lead to cytokine storm . Therefore, the development of new naturaltherapies and repurposing some drugs such as Phenformin and Docosahexaenoic acidthat could compete with COVID-19 for ACE2 binding or inhibit IL-6 activity may possibly help COVID-19 patients avoid a cytokine storm and save their lives through inhibiting IL-6 and preventing SARS-CoV-2 RBD attachment to ACE2. Herein we made a docking based screening for some natural phytochemicals anddrugs that could be repurposed according to our findings to counter COVID-19 cell entry and inhibitthe hyper activation of IL-6. Our results revealed that a five phytochemicalsincluding Epigallocatechin gallate (EGCG) , bromelain, luteolin , vitexin and isovitexin)showed a high binding affinities with best interactions with the active sites of IL-6 .The binding affinities of these phytochemicalsincluding,EGCG , bromelain, luteolin , vitexin and isovitexinwith IL-6 were (-7.7,-6.7, -7.4, -7.2 and -7.3 ), respectively. In addition to ,phenforminshowed a high binding affinity with best interactions with the active sites of IL-6 and ACE2 . The binding affinity of phenformin with IL-6 was (-7.4) and with ACE 2 ( -7.2).Docosahexaenoic acid (DHA) had a moderate binding affinity and moderate interactions with the active sites of IL-6 and had a high binding affinity with best interactions with ACE2 active sites. The binding affinity of Docosahexaenoic acid(DHA)with IL-6 was (-5.3) and with AC2 (-6.3).

COVID-19: Potential of microalgae derrived natural astaxanthin as adjunctive supplement in alleviating cytokine storm

2020 ◽  
Author(s):  
Jayanta Talukdar ◽  
Santanu Dasgupta ◽  
Vinod Nagle ◽  
Bhaskar Bhadra
Keyword(s):  
Immune Response ◽  
Acute Respiratory Distress Syndrome ◽  
Time Use ◽  
Recovery Time ◽  
Distress Syndrome ◽  
Cytokine Storm ◽  
Intervention Measures ◽  
Long Time ◽  
Life Threatening ◽  
Anti Oxidant

The pandemic outbreak of Coronavirus disease (COVID-2019) is a potentially fatal and highly contagious disease. Given that in absence of definitive COVID-19 treatment, and the presence of asymptomatic carriers, the conventional intervention measures to curb the rate of infection and deaths will be highly challenging. Accumulating evidences suggest that excessive reactive inflammation, oxidation, and an exaggerated immune response very likely to contribute to its pathology, leads by a violent immune response cytokine storm and subsequent progression to life threatening acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). Microalgae derived natural astaxanthin (nASX), a well-known potent anti-oxidant and broad-spectrum anti-inflammatory compound with impressive safety profile, is protective against cytokine storm, ALI/ARDS. This article summarizes the most likely benefits of nASX may provide as an adjunctive in attenuation of COVID-19 induced health adversaries based on its putative pathogenesis. There is rationale, pre-clinical evidences of effectiveness and evidence of safety from long-time use for other indications to justify possible inclusion of nASX as adjunctive in combination with primary anti-viral drugs therapy will hugely benefit COVID-19 patients by improving their health and reducing recovery time.

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