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1.
Small Methods ; 5(5): e2001108, 2021 05.
Article in English | MEDLINE | ID: covidwho-1930144

ABSTRACT

During the global outbreak of COVID-19 pandemic, "cytokine storm" conditions are regarded as the fatal step resulting in most mortality. Hemoperfusion is widely used to remove cytokines from the blood of severely ill patients to prevent uncontrolled inflammation induced by a cytokine storm. This article discoveres, for the first time, that 2D Ti3 C2 Tx MXene sheet demonstrates an ultrahigh removal capability for typical cytokine interleukin-6. In particular, MXene shows a 13.4 times higher removal efficiency over traditional activated carbon absorbents. Molecular-level investigations reveal that MXene exhibits a strong chemisorption mechanism for immobilizing cytokine interleukin-6 molecules, which is different from activated carbon absorbents. MXene sheet also demonstrates excellent blood compatibility without any deleterious side influence on the composition of human blood. This work can open a new avenue to use MXene sheets as an ultraefficient hemoperfusion absorbent to eliminate the cytokine storm syndrome in treatment of severe COVID-19 patients.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/drug therapy , Hemoperfusion/methods , Nanostructures/administration & dosage , SARS-CoV-2/immunology , Titanium/administration & dosage , Adsorption , COVID-19/transmission , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/virology , Humans , Interleukin-6/immunology , Nanostructures/chemistry , SARS-CoV-2/isolation & purification , Titanium/chemistry
3.
Clin Lab ; 68(2)2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1687428

ABSTRACT

BACKGROUND: A novel therapy for reducing the cytokines in the circulatory system used for severe COVID-19 cases was hemoperfusion or hemadsorption method. Although the hemoperfusion methods have been shown to be beneficial in the cytokine storm during influenza infection, it is not known to what extent it is successful for COVID-19 patients. Therefore, the purpose of this study is to review the studies on severe COVID-19 treated with the hemoperfusion methods. METHODS: A literature search was conducted using the databases PubMed, Science Direct, and Springer databases. Since the included articles consisted of case reports, case series, and one controlled trial, only the mean of the analyzed data could be calculated. RESULTS: Sixteen studies were included in the narrative review, including 86 patients with severe COVID-19. All the patients had hemoperfusion therapy with following cartridges: CytoSorb®, oXiris®, Biosky filter, SeaStar® CLR filter, HA280, HA330 Jafron©, and resin directed hemadsorption cartridges. Mortality rate, the mean of intubation time, duration in intensive care unit and hospital were 29%, 14.93 days, 17.21 days, and 31.7 days, respectively. The mean values of C-reactive protein and interleukin-6 decreased after hemoperfusion sessions (131.7 to 66.0, 527.5 to 334.7, respectively). CONCLUSIONS: In this narrative review, it is demonstrated that hemadsorption therapy is an alternative salvage treatment method in critically ill COVID-19 patients, but the data must be supported by strong evidence.


Subject(s)
COVID-19 , Hemoperfusion , Critical Illness , Hemadsorption , Humans , SARS-CoV-2
5.
Hemodial Int ; 26(2): 176-182, 2022 04.
Article in English | MEDLINE | ID: covidwho-1570641

ABSTRACT

BACKGROUND: Coronavirus disease-2019 (COVID-19)-related organ failure is partly related to a sepsis-like syndrome and extreme pro-inflammatory cytokine release, named cytokine storm. Therapeutic strategies that prevent the production of or remove the pro-inflammatory cytokines could potentially be an effective therapy in critically afflicted COVID-19 patients. METHODS: In this clinical trial study, from April until June 2020, 68 COVID-19 patients (35 vs. 33 controls) with severe critical symptoms, and PaO2 /FiO2 (P/F) ratio less than 200 mmHg either received a single standard therapy or a combination of standard treatment for COVID-19 combined with hemoperfusion (hemofilter, HA330 D Javfron) for 4 h, in 3 consecutive days. The length of hospital stay and mechanical ventilation, the resolution of radiologic abnormalities, and the mortality rate were defined as the primary outcomes. RESULTS: Demographic characteristics, the acute physiology, and chronic health evaluation score of both groups were similar (p > 0.05). Importantly, we noticed a significant mortality rate reduction in the perfused group compared with controls (37.1% vs. 63.6%, p = 0.02), this positive effect was stronger among those with a P/F ratio higher than 75 (mortality rate of 84.7% for P/F ratio < 75 vs. 15.4% for P/F ratio ≥ 75, p = 0.02). CONCLUSIONS: The results imply that early start of hemoperfusion could be more effective and significantly reduce the mortality rate among COVID-19 patients with critical diseases.


Subject(s)
COVID-19 , Hemoperfusion , COVID-19/therapy , Humans , Renal Dialysis , Respiration, Artificial , SARS-CoV-2
6.
Nephrol Dial Transplant ; 37(4): 673-680, 2022 03 25.
Article in English | MEDLINE | ID: covidwho-1556901

ABSTRACT

BACKGROUND: The Seraph® 100 Microbind® Affinity Blood Filter is a haemoperfusion device that is licensed for the reduction of pathogens, including several viruses, in the blood. It received Emergency Use Authorization for the treatment of severe coronavirus disease 2019 (COVID-19) by the Food and Drug Administration (FDA). Several studies have shown that the blood viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlates with adverse outcomes and removal of the nucleocapsid of the SARS-CoV-2 virus by the Seraph® 100 has been recently demonstrated. The aim of this registry was to evaluate the safety and efficacy of Seraph® 100 treatment for COVID-19 patients. METHODS: Twelve hospitals from six countries representing two continents documented patient and treatment characteristics as well as outcome parameters without reimbursement. Additionally, mortality and safety results of the device were reported. A total of 102 treatment sessions in 82 patients were documented in the registry. Four patients were excluded from mortality analysis due to incomplete outcome data, which were available in the other 78 patients. RESULTS: Overall, a 30-day mortality rate of 46.2% in the 78 patients with complete follow-up was reported. The median treatment time was 5.00 h (4.00-13.42) and 43.1% of the treatments were performed as haemoperfusion only. Adverse events of the Seraph® 100 treatment were reported in 8.8% of the 102 treatments and represented the premature end of treatment due to circuit failure. Patients who died were treated later in their intensive care unit (ICU) stay and onset of COVID symptoms. They also had higher ferritin levels. Multivariate Cox regression revealed that delayed Seraph® 100 treatment after ICU admission (>60 h), as well as bacterial superinfection, were associated with mortality. While average predicted mortality rate according to Sequential Organ Failure Assessment (SOFA) score in ICU patients was 56.7%, the observed mortality was 50.7%. In non-ICU patients, Coronavirus Clinical Characterisation Consortium (4C) score average predicted a mortality rate of 38.0%, while the observed mortality rate was 11.1%. CONCLUSIONS: The treatment of COVID-19 patients with Seraph® 100 is well tolerated and the circuit failure rate was lower than previously reported for kidney replacement therapy (KRT) in COVID-19 patients. Mortality correlated with late initiation of Seraph treatment after ICU admission and bacterial superinfection. Compared with predicted mortality according to 4C and SOFA scores, mortality of Seraph® 100-treated patients reported in the registry was lower.


Subject(s)
COVID-19 , Hemoperfusion , COVID-19/therapy , Critical Care , Humans , Intensive Care Units , Registries , SARS-CoV-2
7.
Artif Organs ; 45(12): 1466-1476, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1526347

ABSTRACT

BACKGROUND: Coronavirus disease-19 (COVID-19) ranges from asymptomatic infection to severe cases requiring admission to the intensive care unit. Together with supportive therapies (ventilation in particular), the suppression of the pro-inflammatory state has been a hypothesized target. Pharmacological therapies with corticosteroids and interleukin-6 (IL-6) receptor antagonists have reduced mortality. The use of extracorporeal cytokine removal, also known as hemoperfusion (HP), could be a promising non-pharmacological approach to decrease the pro-inflammatory state in COVID-19. METHODS: We conducted a systematic review of PubMed and EMBASE databases in order to summarize the evidence regarding HP therapy in COVID-19. We included original studies and case series enrolling at least five patients. RESULTS: We included 11 articles and describe the characteristics of the populations studied from both clinical and biological perspectives. The methodological quality of the included studies was generally low. Only two studies had a control group, one of which included 101 patients in total. The remaining studies had a range between 10 and 50 patients included. There was large variability in the HP techniques implemented and in clinical and biological outcomes reported. Most studies described decreasing levels of IL-6 after HP treatment. CONCLUSION: Our review does not support strong conclusions regarding the role of HP in COVID-19. Considering the very low level of clinical evidence detected, starting HP therapies in COVID-19 patients does not seem supported outside of clinical trials. Prospective randomized data are needed.


Subject(s)
COVID-19/therapy , Cytokines/blood , Hemoperfusion , Inflammation Mediators/blood , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Female , Hemoperfusion/adverse effects , Hemoperfusion/mortality , Humans , Male , Middle Aged , Risk Factors , Treatment Outcome
9.
J Intensive Care Med ; 36(10): 1228-1232, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1405275

ABSTRACT

We present 2 patients with rapidly escalating oxygen requirements from severe acute respiratory syndrome coronavirus 2 infection (COVID-19) treated with the Seraph100 Microbind Affinity Blood Filter under Emergency Use Authorization from the US Federal Drug Administration. The Seraph100 is an extracorporeal hemoperfusion filter previously demonstrated to remove viral particles and pro-inflammatory cytokines from the blood. Treatment with the Seraph100 filter was associated with a rapid improvement in oxygenation and both patients were discharged from the hospital without supplemental oxygen.


Subject(s)
COVID-19 , Hemoperfusion , Pneumonia , Humans , Lung , Pneumonia/therapy , SARS-CoV-2
10.
J Zhejiang Univ Sci B ; 22(9): 701-717, 2021.
Article in English | MEDLINE | ID: covidwho-1405362

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is a major public health event caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has spread widely all over the world. A high proportion of patients become severely or critically ill, and suffer high mortality due to respiratory failure and multiple organ dysfunction. Therefore, providing timely and effective treatment for critically ill patients is essential to reduce overall mortality. Convalescent plasma therapy and pharmacological treatments, such as aerosol inhalation of interferon-α (IFN-α), corticosteroids, and tocilizumab, have all been applied in clinical practice; however, their effects remain controversial. Recent studies have shown that extracorporeal therapies might have a potential role in treating critically ill COVID-19 patients. In this review, we examine the application of continuous renal replacement therapy (CRRT), therapeutic plasma exchange (TPE), hemoadsorption (HA), extracorporeal membrane oxygenation (ECMO), and extracorporeal carbon dioxide removal (ECCO2R) in critically ill COVID-19 patients to provide support for the further diagnosis and treatment of COVID-19.


Subject(s)
COVID-19/therapy , Extracorporeal Circulation/methods , Extracorporeal Membrane Oxygenation , SARS-CoV-2 , COVID-19/complications , Carbon Dioxide/isolation & purification , Critical Illness , Cytokine Release Syndrome/therapy , Hemoperfusion , Humans , Immunization, Passive , Plasma Exchange , Renal Replacement Therapy
11.
Int J Mol Sci ; 22(4)2021 Feb 23.
Article in English | MEDLINE | ID: covidwho-1389391

ABSTRACT

Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.


Subject(s)
Cotton Fiber , Endotoxins/blood , Endotoxins/isolation & purification , Hemoperfusion/methods , Immobilization/methods , Polymyxin B/chemistry , Sepsis/therapy , Shock, Septic/therapy , Adsorption , Animals , COVID-19/therapy , Endotoxemia/blood , Endotoxemia/therapy , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Idiopathic Pulmonary Fibrosis/therapy , Immobilization/instrumentation , Sepsis/blood , Shock, Septic/blood
13.
Blood Purif ; 51(5): 410-416, 2022.
Article in English | MEDLINE | ID: covidwho-1362021

ABSTRACT

INTRODUCTION: Systematic inflammatory response occurred in some critically ill patients with COVID-19. Cytokine reduction by hemadsorption is a mechanism of treatment. However, whether CytoSorb hemoperfusion works for critically ill COVID-19 patients remains unknown. MATERIALS AND METHODS: We observed case series of critically ill COVID-19 patients receiving CytoSorb hemoperfusion as rescue therapy from 3 hospitals in Hubei, China from February 28, 2020, to April 7, 2020. Their demographic, laboratory, and clinical data were collected. The parameters for organ function and IL-6 levels were compared before and after treatments. RESULTS: A total of 10 cases were included. The median age of the patients was 67.7 years (range = 50-85) with APACHE II (23.5) and SOFA (11.4). Patients received a median of 3 attempts of hemoperfusion (range = 1-6). The median CytoSorb perfusion time was 47 h (12-92 h). The level of IL-6 significantly decreased after treatments (712.6 [145-5,000] vs. 136.7 [46.3-1,054] pg/mL, p = 0.005). Significant improvement was found in PaO2/FiO2 (118 [81-220] vs. 163 [41-340] mm Hg, p = 0.04) and lactate levels (2.5 [1-18] vs. 1.7 [1.1-10] mmol/L, p = 0.009). The hemodynamics measured by norepinephrine/MAP slightly improved after treatment (17 [0-68] vs. 8 [0-39], p = 0.09). Albumin mildly decreased after CytoSorb. No significant changes were found in red blood cell counts, white cell counts, and platelets. CONCLUSION: Treatment with CytoSorb in critically ill COVID-19 patients was associated with decreased IL-6 improvement in oxygenation. However, these effects cannot be confirmed as the direct effects of CytoSorb owing to lack of controls. Establishing causality requires large-scale randomized clinical trials.


Subject(s)
COVID-19 , Hemoperfusion , Aged , Aged, 80 and over , COVID-19/therapy , Critical Illness/therapy , Hemadsorption , Humans , Interleukin-6 , Middle Aged
16.
Blood Purif ; 51(4): 317-320, 2022.
Article in English | MEDLINE | ID: covidwho-1309872

ABSTRACT

There is an urgent need for therapeutic interventions to alter the course of critically ill coronavirus disease 2019 (CO-VID-19) patients. We report our experience with the Seraph-100 Microbind Affinity Blood Filter (Seraph-100) in 4 patients with COVID-19 early in the course of their critical respiratory illnesses. Patients were diagnosed with COVID-19 and were admitted to intensive care with worsening respiratory failure but did not require dialysis or vasopressors. Patients had to have a PaO2 to FiO2 (P/F ratio) <150 to qualify for hemoperfusion therapy. All patients received standard medical therapy including oral vitamins C and D and zinc in addition to intravenous dexamethasone and remdesivir. Patients received a single 5- to 7-h session with Seraph-100 on a conventional dialysis machine (Fresenius 2008T) via a nontunneled central venous dialysis catheter with a goal of processing at least 100 L of blood. Patients received weight-based subcutaneous enoxaparin anticoagulation, as well as systemic intravenous heparin (70 units/kg), just prior to hemofiltration. Treatment with Seraph-100 hemoperfusion was well tolerated, and all patients were able to finish their prescribed therapy. All patients treated with Seraph-100 survived to be discharged from the hospital. Well-designed clinical trials are needed to determine the overall safety and efficacy of the Seraph-100 Microbind Affinity Blood Filter in COVID-19 patients.


Subject(s)
COVID-19 , Hemoperfusion , COVID-19/therapy , Critical Illness/therapy , Humans , Renal Dialysis , SARS-CoV-2
18.
J Med Virol ; 93(10): 5742-5755, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1296839

ABSTRACT

Some previous studies suggested that the plasma exchange (PE) and hemoperfusion (HP) played a cardinal role in the treatment of severe coronavirus disease 2019 (COVID-19) cases by diminishing the cytokine storm. This study aimed to assess the effects of PE and HP on cytokine storms in patients with severe COVID-19 through a systematic scoping review. Four Electronic databases (Medline [accessed from PubMed], Scopus, Science Direct, and Cochrane library) were searched systematically on February 2, 2021, using MESH terms and related keywords in the English language. Considering the titles and abstracts, unrelated studies were excluded. The full texts of the remained studies were evaluated by authors, independently. Then, their findings were assessed and reported. A total of 755 articles were obtained within the first step of searching, and 518 remained after removing the duplications. Through the title and abstract screening, 438 were removed. Of the rest, 59 papers were excluded. Finally, after reading the full text of the remained articles, 21 were included in data extraction. Most of the previously reported evidence were case reports and case series. Findings were summarized in two categories. The first category encompassed nine studies regarding HP and continuous renal replacement therapy, and the second category included twelve studies about PE. The results revealed that HP and PE within the cytokine storm phase would be beneficial with a high probability in the treatment of severely ill COVID-19 patients. Highlights Some studies showed that plasma exchange (PE) and hemoperfusion (HP) played an important role in the treatment of patients with severe COVID-19 disease. The results of this systematic scoping review revealed that HP and PE within the cytokine storm phase would be beneficial with a high probability in the treatment of severely ill COVID-19 patients.


Subject(s)
COVID-19/therapy , Hemoperfusion , Plasma Exchange , Continuous Renal Replacement Therapy , Cytokine Release Syndrome/therapy , Humans , SARS-CoV-2 , Treatment Outcome
19.
Front Immunol ; 12: 665824, 2021.
Article in English | MEDLINE | ID: covidwho-1273337

ABSTRACT

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is characterized by hypercytokinemia leading to overwhelming inflammation. We describe the use of a hemadsorption device as part of the supportive treatment for cytokine storm.


Subject(s)
COVID-19/complications , Hemoperfusion/methods , Systemic Inflammatory Response Syndrome/therapy , Adolescent , COVID-19/therapy , Humans , Male , SARS-CoV-2
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