scholarly journals The Use of CytoSorb Therapy in Critically Ill COVID-19 Patients: Review of the Rationale and Current Clinical Experiences

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Juan Carlos Ruiz-Rodríguez ◽  
Zsolt Molnar ◽  
Efthymios N. Deliargyris ◽  
Ricard Ferrer
Keyword(s):  
Critically Ill ◽  
Host Response ◽  
Blood Purification ◽  
Vital Organ ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Clinical Experiences ◽  
Health Crisis ◽  
Considerable Evidence ◽  
Beneficial Effects

The COVID-19 pandemic has led to the biggest global health crisis of our lifetime. There is accumulating evidence that a substantial number of critically ill COVID-19 patients exhibit a dysregulated host response manifesting as cytokine storm or cytokine release syndrome, which in turn contributes to the high observed rates of mortality. Just as in other hyperinflammatory conditions, extracorporeal cytokine removal may have potential beneficial effects in this subgroup of COVID-19 patients. The CytoSorb blood purification device is the most extensively investigated cytokine removal platform with considerable evidence suggesting that early intervention can provide rapid hemodynamic stabilization and improvement in vital organ functions. The purpose of this review is to provide an overview of the pathophysiological background of hyperinflammation in COVID-19 and to summarize the currently available evidence on the effects of hemoadsorption in these patients.

scholarly journals Use of heparin in patients with severe COVID-19: What is the evidence?

2021 ◽  
Vol 10 (6) ◽  
pp. e28910615820
Author(s):  
Vitória Ribeiro Dantas Marinho ◽  
Camila Vilar Oliveira Villarim ◽  
Laura Cristina Costa e Silva ◽  
André Luiz Costa e Silva ◽  
Irami Araújo-Neto ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Web Of Science ◽  
Pulmonary Thromboembolism ◽  
Cytokine Release ◽  
Beneficial Effects ◽  
Heparin Administration ◽  
Rapid Spread ◽  
New Research ◽  
D Dimer

The rapid spread of coronavirus disease (COVID-19) worldwide urges the need for studies on the illness and its management. The COVID-19 infection leads to hypercoagulation due to inflammatory cytokine release and D-dimer increase in critically ill patients, resulting in pulmonary thromboembolism (PE) and venous thromboembolism (VTE) evolving to sepsis and death. The study evaluated the currently existing evidence on heparin administration in patients with severe COVID-19. An integrative literature review was done by searching for scientific studies in the PubMed, Scopus, Embase, and Web of Science databases. The analyzed studies showed that heparin use in critically ill patients could efficiently prevent thrombotic events and reduce the exacerbated inflammatory process. However, further investigation on the effect on patients is still needed. The use of heparin in critically ill COVID-19 patients has been prescribed increasingly by doctors. But its use has not yet had its outcomes well established in the literature. Therefore, deeper investigations and new research development are needed to clarify potential beneficial effects.

Systematic Review on Treatment Trials of Tocilizumab- A Repurposing Drug Against COVID-19

2021 ◽  
Vol 16 ◽  
Author(s):  
Shilpita Banerjee ◽  
Ajit Kumar Mahapatra
Keyword(s):  
Individual Patient Data ◽  
Critical Conditions ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Health Crisis ◽  
Randomized Controlled ◽  
Global Issue ◽  
Humanized Monoclonal Antibody ◽  
Integral Role ◽  
Rate Of Recovery

Background: Coronavirus disease (COVID-19) that is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a global issue today. There exists an ongoing health crisis all over the world and efficacious drugs against COVID-19 are not available yet. Therefore, on an urgent basis, scientists are looking for safe and efficacious drugs against SARS-CoV-2. Methods: The reported individual patient data and clinical outcomes including rate of recovery and mortality, patients’ characteristics and complications are reviewed. Randomized controlled trials, single center cohort studies and different case studies are provided and PICO model is used to illustrate the outcomes. Results: There exists several FDA (U.S Food and Drug Administration) approved anti corona virus drugs that sometimes are unsuccessful to cure COVID-19 critical conditions. It has been observed that a humanized monoclonal antibody, Tocilizumab (licensed for the treatment of rheumatoid arthritis), targeting the interleukin-6 (IL-6) receptor, has an integral role in the treatment of COVID-19. Conclusion: The cause behind the mortality of COVID-19 patients was found to be the Cytokine Release Syndrome (CRS). So, beside other antiviral drugs, the utilization of tocilizumab should also be considered as it can effectively block IL-6 and reduce the inflammatory signal.

scholarly journals COVID-19 and immunomodulation in IBD

Gut ◽  
2020 ◽  
Vol 69 (7) ◽  
pp. 1335-1342 ◽  
Author(s):  
Markus F Neurath
Keyword(s):  
Cell Activation ◽  
Distress Syndrome ◽  
Biological Therapy ◽  
Immune Cell ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Health Crisis ◽  
Immune Cell Activation ◽  
Lethal Complications ◽  
Key Questions

The current coronavirus pandemic is an ongoing global health crisis due to COVID-19, caused by severe acute respiratory syndrome coronavirus 2. Although COVID-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to COVID-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of COVID-19. Here, the current understanding of the pathophysiology of COVID-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.

scholarly journals Anti-IL-6 versus Anti-IL-6R Blocking Antibodies to Treat Acute Ebola Infection in BALB/c Mice: Potential Implications for Treating Cytokine Release Syndrome

2020 ◽  
Author(s):  
Reid Rubsamen ◽  
Scott Burkholz ◽  
Christopher Massey ◽  
Trevor Brasel ◽  
Tom Hodge ◽  
...  
Keyword(s):  
Host Response ◽  
Viral Infections ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Important Mediator ◽  
Acute Viral Infection ◽  
Clinical Benefits ◽  
Coronavirus Infection ◽  
Blocking Antibodies

ABSTRACTCytokine release syndrome (CRS) is known to be a factor in morbidity and mortality associated with acute viral infections including those caused by filoviruses and coronaviruses. IL-6 has been implicated as a cytokine negatively associated with survival after filovirus and coronavirus infection. However, IL-6 has also been shown to be an important mediator of innate immunity and important for the host response to an acute viral infection. Clinical studies are now being conducted by various researchers to evaluate the possible role of IL-6 blockers to improve outcomes in critically ill patients with CRS. Most of these studies involve the use of anti-IL-6R monoclonal antibodies (α-IL-6R mAbs). We present data showing that direct neutralization of IL-6 with an α-IL-6 mAb in a BALB/c Ebolavirus (EBOV) challenge model produced a statistically significant improvement in outcome compared with controls when administered within the first 24 hours of challenge and repeated every 72 hours. A similar effect was seen in mice treated with the same dose of α-IL-6R mAb when the treatment was delayed 48 hrs post-challenge. These data suggest that direct neutralization of IL-6, early during the course of infection, may provide additional clinical benefits to IL-6 receptor blockade alone during treatment of patients with virus-induced CRS.

scholarly journals Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics

2020 ◽  
Vol 222 (9) ◽  
pp. 1444-1451 ◽  
Author(s):  
Wenjun Wang ◽  
Xiaoqing Liu ◽  
Sipei Wu ◽  
Sibei Chen ◽  
Yimin Li ◽  
...  
Keyword(s):  
Critically Ill ◽  
Virus Disease ◽  
Pulmonary Inflammation ◽  
Case Series ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Disease Characteristics ◽  
Medical University ◽  
Termination Date

Abstract Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.

scholarly journals Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 91
Author(s):  
Alexandra Pum ◽  
Maria Ennemoser ◽  
Tiziana Adage ◽  
Andreas J. Kungl
Keyword(s):  
Host Response ◽  
Distress Syndrome ◽  
Therapeutic Strategies ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Severe Respiratory Distress ◽  
Cytokines And Chemokines ◽  
Severe Respiratory Distress Syndrome ◽  
Harmful Effects

The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal consequences. Although several factors of this infection and its consequences are not completely clear, the presence and involvement of specific chemokines is undoubtedly crucial for the development and progression of COVID-19. Cytokine storm and the often-resulting cytokine release syndrome (CRS) are pathophysiological hallmarks in COVID-19 infections related to its most severe and fatal cases. In this hyperinflammatory event, chemokines and other cytokines are highly upregulated and are therefore not fulfilling their beneficial function in the host response anymore but causing harmful effects. Here, we present the recent views on the involvement of chemokines and selected cytokines in COVID-19 and the therapeutics currently in clinical development targeting or interfering with them, discussing their potentials in the treatment of COVID-19 infections.

scholarly journals Sarilumab (IL-6R antagonist) in critically ill patients with cytokine release syndrome by SARS-CoV2

Medicine ◽  
2021 ◽  
Vol 100 (19) ◽  
pp. e25923
Author(s):  
Hèctor Corominas ◽  
Ivan Castellví ◽  
César Diaz-Torné ◽  
Laia Matas ◽  
David de la Rosa ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Cytokine Release ◽  
Cytokine Release Syndrome

scholarly journals The definition and risks of Cytokine Release Syndrome-Like in 11 COVID-19-Infected Pneumonia critically ill patients: Disease Characteristics and Retrospective Analysis

2020 ◽  
Author(s):  
Wang Wenjun ◽  
Liu Xiaoqing ◽  
Wu Sipei ◽  
Lie Puyi ◽  
Huang Liyan ◽  
...  
Keyword(s):  
Nk Cells ◽  
Retrospective Analysis ◽  
Critically Ill ◽  
Immune Cells ◽  
Critically Ill Patients ◽  
Peripheral Blood ◽  
Pulmonary Inflammation ◽  
Clinical Treatment ◽  
Cytokine Release ◽  
Cytokine Release Syndrome

IMPORTANCECOVID-19-infected pneumonia patients with severe immune abnormalities and risk of cytokine release syndrome. The definition, prevention, and treatment of COVID-19-infected pneumonia in critically ill patients with cytokine release syndrome symptoms is an important problem.OBJECTIVETo define the cytokine release syndrome-like (CRSL) in COVID-19-infected pneumonia in critically ill patients and study the risk factors and therapeutic strategies.DESIGN, SETTING, AND PARTICIPANTSThis is a retrospective, single center case study of 11 COVID-19-infected pneumonia patients with acute respiratory distress syndrome (ARDS) from The First Affiliated Hospital of Guangzhou Medical University in China from January 26, 2020 to February 18, 2020. The follow-up termination date was February 19, 2020.EXPOSERESEleven COVID-19-infected pneumonia patients with ARDS in the ICU. Some of these patients also had cytokine release syndrome-like (CRSL). Immunologic detection, clinical characteristics, and clinical treatment analysis were carried out to define the CRSL in these COVID-19-infected pneumonia patients.MAIN OUTCOMES AND MEASURESClinical, radiological, immunology (including immune cell subsets and cytokines analysis), laboratory, and clinical treatment data were collected and analyzed. The critically ill patients with CRSL were defined. Prevention and control strategies were studied.RESULTSOf 11 critically ill patients in the ICU, the median age was 58 (Inter-Quartile Range{IQR}, 49–72; range, 26–72 years), and 10 (83.3%) were males. Ten (83.3%) patients had extensive pulmonary inflammation and ARDS (the median time from the first symptom to ARDS was 10.0 d), fever, and hypoxia; four (28.6%) patients experienced shock. The lymphocyte subpopulations including CD3 (CD3 + CD45+), CD4 (CD3 + CD4+), CD8 (CD3 + CD8+), NK (CD3-CD16 + CD56 +), Tregs (CD4 + CD25 + CD127 low), B lymphocyte (CD3-CD19 +) cells; and cytokines including IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ were detected at different time points. All of the patients had a decrease of CD3 (IQR,169–335; range, 50–635 cells/μL), CD4 (IQR,101–303; range, 27–350 cells/μL), CD8 (IQR, 33–141; range, 21–277 cells/μL); ten (90.9%) patients have a decrease in NK immune cells (IQR,8–72; range, 5–170 cells/μL); both of Tregs (IQR,3.3-7.8;rang,2.3-9.4%) and B immune cells (IQR,61-146; rang,44-222 cells/μL)were decreased in two (18.2%) patients. And nine patients were increase in CD4 / CD8 (IQR,3.3–7.8%; range, 2.3–9.7%). All patients had a significant increase of IL-6 (IQR,14.26-92.2; range, 4.58–1182.91ng/L). Eight (72.7%) patients were determined to have CRSL characteristics, including pulmonary inflammation, fever, a decrease of CD4, CD8, and NK cells; an increase of CD4/CD8, a significant increase of IL-6, and the dysfunction of non-pulmonary organs. The numbers of CD4, CD8, and NK cells and the level of IL-6 in peripheral blood were correlated with the area of pulmonary inflammation in CT images (P<0.05). Mechanical-ventilation used to increase blood oxygen concentration could increased the numbers of CD4 (after Vs before ventilation=259±53 VS 507±101; P=0.013, and CD8 (after Vs before ventilation=193±38 VS 279±63; P=0.048), while decreasing the level of IL-6 (after Vs before ventilation=223.2± 89.9 VS 26.8±10; P=0.041). The increased of IL-6 was occurred earlier than the decrease of CD4·, CD8 in the patients with rapidly worsened after ICU.CONCLUSIONS AND RELEVANCEIn this retrospective analysis of 11 critically ill pneumonia patients infected with COVID-19, we defined and identified eight patients (72.7%) with cytokine release syndrome-like (CRSL). We found that a large area of lung injury (≥50%) with an decrease of CD4, CD8 (Lower than 50% minimum normal range) and increase of IL-6 in peripheral blood was the highest risk factor of CRSL. IL-6 was a early indicators of CRSL in COVID-19-infected pneumonia. We also found that reduce injury to the lung is a useful method to prevent and improve COVID-19-infected pneumonia-related CRSL in critically ill pneumonia patients.

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