scholarly journals A digital protein microarray for COVID-19 cytokine storm monitoring

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Yujing Song ◽  
Yuxuan Ye ◽  
Shiuan-Haur Su ◽  
Andrew Stephens ◽  
Tao Cai ◽  
...  
Keyword(s):  
Critically Ill ◽  
Proinflammatory Cytokines ◽  
Protein Microarray ◽  
Cytokine Storm ◽  
Microfluidic Immunoassay ◽  
Digital Microfluidic

A digital microfluidic immunoassay platform enables rapid multiplex quantification of proinflammatory cytokines in serum for critically ill COVID-19 patients.

scholarly journals Can the cytokine adsorber CytoSorb® help to mitigate cytokine storm and reduce mortality in critically ill patients? A propensity score matching analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina Scharf ◽  
Ines Schroeder ◽  
Michael Paal ◽  
Martin Winkels ◽  
Michael Irlbeck ◽  
...  
Keyword(s):  
Propensity Score ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Wilcoxon Test ◽  
Relative Reduction ◽  
Cytokine Storm ◽  
Saps Ii ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1

Abstract Background A cytokine storm is life threatening for critically ill patients and is mainly caused by sepsis or severe trauma. In combination with supportive therapy, the cytokine adsorber Cytosorb® (CS) is increasingly used for the treatment of cytokine storm. However, it is questionable whether its use is actually beneficial in these patients. Methods Patients with an interleukin-6 (IL-6) > 10,000 pg/ml were retrospectively included between October 2014 and May 2020 and were divided into two groups (group 1: CS therapy; group 2: no CS therapy). Inclusion criteria were a regularly measured IL-6 and, for patients allocated to group 1, CS therapy for at least 90 min. A propensity score (PS) matching analysis with significant baseline differences as predictors (Simplified Acute Physiology Score (SAPS) II, extracorporeal membrane oxygenation, renal replacement therapy, IL-6, lactate and norepinephrine demand) was performed to compare both groups (adjustment tolerance: < 0.05; standardization tolerance: < 10%). U-test and Fisher’s-test were used for independent variables and the Wilcoxon test was used for dependent variables. Results In total, 143 patients were included in the initial evaluation (group 1: 38; group 2: 105). Nineteen comparable pairings could be formed (mean initial IL-6: 58,385 vs. 59,812 pg/ml; mean SAPS II: 77 vs. 75). There was a significant reduction in IL-6 in patients with (p < 0.001) and without CS treatment (p = 0.005). However, there was no significant difference (p = 0.708) in the median relative reduction in both groups (89% vs. 80%). Furthermore, there was no significant difference in the relative change in C-reactive protein, lactate, or norepinephrine demand in either group and the in-hospital mortality was similar between groups (73.7%). Conclusion Our study showed no difference in IL-6 reduction, hemodynamic stabilization, or mortality in patients with Cytosorb® treatment compared to a matched patient population.

scholarly journals The Systematic Effect of Mesenchymal Stem Cell Therapy in Critical COVID-19 Patients: A Prospective Double Controlled Trial

2021 ◽  
Vol 30 ◽  
pp. 096368972110249
Author(s):  
G Adas ◽  
Z Cukurova ◽  
K Kart Yasar ◽  
R Yilmaz ◽  
N Isiksacan ◽  
...  
Keyword(s):  
Growth Factors ◽  
Critically Ill ◽  
Inflammatory Cytokines ◽  
Clinical Manifestations ◽  
Systematic Effect ◽  
Cytokine Storm ◽  
Group 3 ◽  
Anti Inflammatory ◽  
Group 2 ◽  
Group 1

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-β, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.

Hydrocortisone vs Tocilizumab Effects on Cytokine Storm in Critically Ill Patients with COVID-19.

2020 ◽  
Author(s):  
Maria Vargas ◽  
Pasquale Buonanno ◽  
Carmine Iacovazzo ◽  
Gaetano Di Spigna ◽  
Daniela Spalletti ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Severe Pneumonia ◽  
Cytokine Storm ◽  
Tnf Α ◽  
Speed Up ◽  
The Impact ◽  
Late Stages

Abstract Introduction: Patients with severe pneumonia due COVID-19 are reported to have substantially lower lymphocyte counts and higher plasma concentrations of a number of inflammatory cytokines. In the late stages of COVID-19, cytokine storms are the mainly cause of disease progression and death. We performed a prospective observational study to evaluate the impact of tocilizumab and hydrocortisone on cytokine storm in critically ill patients with COVID-19.Methods: We included all adult patients with laboratory-confirmed COVID-19 infection and severe respiratory failure admitted to our ICU from March 10 to April 30. As therapeutic options, patients received tocilizumab od hydrocortisone. The primary end point was the evaluation of cytokine storm in terms of variation of the IL-6 and IL-6R, sgp130 and TNF-α concentrations during time to different treatment.Results: Eight patients received tocilizumab while 15 patients received hydrocortisone. IL-6 levels were lower in the hydrocortisone group with statistical significance was found at the days 2, 3, 8 and 9. The levels of IL-6R were lower during the days in the hydrocortisone group with statistical significance at days 1, 2, 3, 4, 5, 6, 8 and 10. Hydrocortisone group had higher levels of TNF-α at days 2, 3 and 4. The levels of sgo130 between tocilizumab and hydrocortisone groups were not statistically different during the days.Conclusions: In critically ill patients with severe COVID-19, the use of hydrocortisone allowed a better control of the cytokine storms, was further associated to less days of curarization, pronation and length of stay in ICU, and speed up the time to get negative RT-PCR swab.

scholarly journals Weather the Cytokine Storm: A Report of Successful Management of a Colon Cancer Survivor and a Critically Ill Patient with COVID-19

2020 ◽  
Vol 13 (2) ◽  
pp. 754-759
Author(s):  
Mansoor Khalid ◽  
Tarek Dernaika ◽  
Lirin Jacob ◽  
Pavan Annamaraju ◽  
Achuta K. Guddati
Keyword(s):  
Critically Ill ◽  
Cancer Survivor ◽  
Critically Ill Patient ◽  
Cytokine Storm ◽  
Ventilator Support ◽  
X Ray ◽  
Chest X Ray ◽  
Underlying Mechanisms ◽  
Poor Outcomes

Patients with novel corona virus infection (COVID-19) can develop acute respiratory failure secondary to acute respiratory distress syndrome. Cytokine storm is suggested as one of underlying mechanisms for the rapid clinical decline. Immunocompromised patients and cancer patients are at particular risk for poor outcomes due to COVID-19 infection. This case report describes the presentation and clinical course of a cancer survivor who became critically ill and required mechanical ventilation. The patient was treated with hydroxychloroquine, azithromycin, and ceftriaxone; however, he remained febrile, hypoxemic, continued to require full mechanical ventilator support and his chest X-ray showed increased bilateral infiltrates. The patient was treated with tocilizumab, after which he improved and was successfully extubated. This report illustrates a possible role of tocilizumab in management of cytokine storm in critically ill patients with COVID-19 infection.

scholarly journals A highly efficient bead extraction technique with low bead number for digital microfluidic immunoassay

2016 ◽  
Vol 10 (1) ◽  
pp. 011901 ◽  
Author(s):  
Cheng-Yeh Huang ◽  
Po-Yen Tsai ◽  
I-Chin Lee ◽  
Hsin-Yun Hsu ◽  
Hong-Yuan Huang ◽  
...  
Keyword(s):  
Extraction Technique ◽  
Highly Efficient ◽  
Microfluidic Immunoassay ◽  
Digital Microfluidic

scholarly journals Continuous extracorporeal treatments in a dialysis patient with COVID-19

2020 ◽  
Author(s):  
Yoshihito Nihei ◽  
Hajime Nagasawa ◽  
Yusuke Fukao ◽  
Masao Kihara ◽  
Seiji Ueda ◽  
...  
Keyword(s):  
Critically Ill ◽  
Distress Syndrome ◽  
Polymyxin B ◽  
Cytokine Storm ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Continuous Hemodiafiltration ◽  
Timely Initiation ◽  
Direct Hemoperfusion ◽  
Treatment Approaches ◽  
Extracorporeal Treatment

Abstract The coronavirus disease 2019 (COVID-19) pandemic is now a major global health threat. More than half a year have passed since the first discovery of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), no effective treatment has been established especially in intensive care unit. Inflammatory cytokine storm caused by SARS-CoV-2 infection has been reported to play a central role in COVID-19; therefore, treatments for suppressing cytokines, including extracorporeal treatments, are considered to be beneficial. However, until today the efficacy of removing cytokines by extracorporeal treatments in patients with COVID-19 is unclear. Herein, we report our experience with a 66-year-old male patient undergoing maintenance peritoneal dialysis who became critically ill with COVID-19 and underwent several extracorporeal treatment approaches including plasma exchange, direct hemoperfusion using a polymyxin B-immobilized fiber column and continuous hemodiafiltration. Though the patient developed acute respiratory distress syndrome (ARDS) repeatedly and subacute cerebral infarction and finally died for respiratory failure on day 30 after admission, these attempts appeared to dampen the cytokine storm based on the observed decline in serum IL-6 levels and were effective against ARDS and secondary haemophagocytic lymphohistiocytosis. This case suggests the significance of timely initiation of extracorporeal treatment approaches in critically ill patients with COVID-19.

scholarly journals Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19

2021 ◽  
Author(s):  
Jordana Grazziela A. Coelho dos Reis ◽  
Geovane Marques Ferreira ◽  
Alice Aparecida Lourenco ◽  
Agata Lopes Ribeiro ◽  
Camila Pacheco da Silveira Martins da Mata ◽  
...  
Keyword(s):  
Critically Ill ◽  
Ex Vivo ◽  
Tracheal Aspirate ◽  
Inflammatory Activity ◽  
Dependent Manner ◽  
Cytokine Storm ◽  
Next Of Kin ◽  
Anti Inflammatory ◽  
Inflammatory Effect ◽  
Tracheal Aspirates

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic, antiviral, and anti-inflammatory effect of BromAc in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. Method: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine storm analysis was performed. Results: BromAc displayed a robust mucolytic effect in a dose dependent manner. BromAc showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1RA and total reduction for IL-9 compared to NAC alone and control. BromAc acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250ug. Conclusion: These results indicate robust mucolytic and anti-inflammatory effect of BromAc in tracheal aspirates from critically ill COVID-19 patients, indicating its potential as a therapeutic strategy to COVID-19.

scholarly journals COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and may be modified by dexamethasone

2021 ◽  
Author(s):  
Aartik Sarma ◽  
Stephanie A. Christenson ◽  
Eran Mick ◽  
Catherine DeVoe ◽  
Thomas Deiss ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Tract ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Host Response ◽  
Lower Respiratory Tract ◽  
Transcriptional Profiling ◽  
Cytokine Storm

AbstractWe performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with ARDS from COVID-19 or other etiologies, or without ARDS. We found no evidence of cytokine storm but instead observed complex host response dysregulation driven by genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone. Compared to other viral ARDS, COVID-19 was characterized by impaired interferon-stimulated gene expression.

scholarly journals Early Tocilizumab Dosing is Associated with Improved Survival In Critically Ill Patients Infected With Sars-CoV-2

2020 ◽  
Author(s):  
Russell M. Petrak ◽  
Nicholas W. Van Hise ◽  
Nathan C. Skorodin ◽  
Robert M. Fliegelman ◽  
Vishnu Chundi ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inflammatory Markers ◽  
Standard Of Care ◽  
Control Group ◽  
Cytokine Storm ◽  
Novel Coronavirus ◽  
Multi Center Study ◽  
Center Study

AbstractBackgroundSARS-CoV-2 is a novel coronavirus that has rapidly expanded to become a pandemic, resulting in millions of deaths worldwide. The cytokine storm is caused by the release of inflammatory agents and results in a physiologic disruption. Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with SARS-CoV-2.MethodsThis was a multi-center study of patients infected with SARS-CoV-2, admitted between 3/13/20 and 4/16/20, requiring mechanical ventilation. Parameters that were evaluated included age, sex, race, usage of steroids, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within one (1) day of intubation. Late dosing was defined as a dose administered greater than one (1) day after intubation. A control group that was treated only with standard of care, and without tocilizumab, was utilized for comparison (untreated).FindingsWe studied 118 patients who required mechanical ventilation. Eighty-one (81) received tocilizumab, compared to 37 who were untreated. Early tocilizumab therapy was associated with a statistically significant decrease in mortality as compared to patients who were untreated (p=0.003). Dosing tocilizumab late was associated with an increased mortality compared to the untreated group (p=0.006).InterpretationEarly tocilizumab administration was associated with decreased mortality in critically ill SARS-Co-V-2 patients, but a potential detriment was suggested by dosing later in a patient’s course.FundingThis work did not receive outside funding or sponsorship.

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