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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
2.
Blood Purif ; 51(11): 879-888, 2022.
Article in English | MEDLINE | ID: covidwho-1685776

ABSTRACT

INTRODUCTION: Currently, the effect of hemoperfusion on outcome in severe COVID-19 patients is still unknown. Therefore, we aimed to investigate the effects of early HA-330 hemoperfusion in severe COVID-19 patients. METHODS: We conducted a single center, prospective cohort study on patients who were diagnosed with severe COVID-19 patients and admitted to ICU. Patients in hemoperfusion group (defined as patients who were treated with hemoperfusion therapy at least 3 sessions in combination with standard therapy) were compared with the control group (defined as patients who received standard treatment alone or received less than 3 sessions of hemoperfusion therapy). The primary outcome was daily sequential organ failure assessment (SOFA) scores. Secondary outcomes were all-cause mortality at 28 days, mechanical ventilator-free day, daily C-reactive protein (CRP), oxygenation (defined by PaO2/FiO2 ratio), and severity score of lung infiltration on the chest X-ray (CXR RALE score). All outcomes were adjusted by regression analysis to reduce the confounders due to some difference in baseline characteristics. RESULTS: A total number of 29 severe and critical COVID-19 confirmed patients were enrolled. Fifteen patients were defined as hemoperfusion group and 14 were control group. The median of CRP and SOFA score at the baseline (the day after severe pneumonia diagnosis or before hemoperfusion) in hemoperfusion and control groups were comparable, 96.79 mg/L and 87.3 mg/L, p = 0.53, 3.53 ± 0.99 versus 4.3 ± 1.89, p = 0.15, respectively. Clinical improvement associated with decreased SOFA score and improvement of CXR RALE score were found in hemoperfusion group compared to control group (p = 0.008 and p = 0.005, respectively). The 28-day mortality rate was significantly lower in hemoperfusion group compared to control group (6.67% vs. 85.71%, p < 0.001) and the adjusted hazard ratio of death was 0.017 (95% confidence interval = 0.008-0.351, p = 0.008). CONCLUSIONS: The addition of early HA-330 hemoperfusion to standard therapy improved severity of organ failure and might reduce the mortality rate. However, the results were affected by the baseline confounders and limited sample size.


Subject(s)
COVID-19 , Hemoperfusion , Humans , Hemoperfusion/methods , COVID-19/therapy , Prospective Studies , Respiratory Sounds , Organ Dysfunction Scores
3.
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
5.
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
7.
Blood Purif ; 51(1): 47-54, 2022.
Article in English | MEDLINE | ID: covidwho-1186414

ABSTRACT

INTRODUCTION: Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may complicate COVID-19. However, the role of endotoxin adsorbent (EA) therapy to mitigate organ dysfunction in COVID-19 has not been explored. METHODS: We conducted a retrospective observational study in COVID-19 patients who received EA therapy at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between March 13 and April 17, 2020. Relevant clinical and laboratory data were collected by inpatient chart review. RESULTS: Among 147 hospitalized COVID-19 patients, 6 patients received EA therapy. All of the 6 patients had severe COVID-19 infection with acute respiratory distress syndrome (ARDS). Among these, 5 of them were mechanically ventilated and 4 had complications of secondary bacterial infection. The endotoxin activity assay (EAA) results of pre-EA therapy ranged from 0.47 to 2.79. The choices of EA therapy were at the discretion of attending physicians. One patient was treated with oXiris® along with continuous renal replacement therapy, and the others received polymyxin B hemoperfusion sessions. All patients have survived and were finally free from the mechanical ventilation as well as had improvement in PaO2/FiO2 ratio and decreased EAA level after EA therapy. CONCLUSIONS: We demonstrated the clinical improvement of severe COVID-19 patients with elevated EAA level upon receiving EA therapy. However, the benefit of EA therapy in COVID-19 ARDS is still unclear and needs to be elucidated with randomized controlled study.


Subject(s)
COVID-19/therapy , Endotoxemia/therapy , Hemoperfusion/methods , SARS-CoV-2 , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Adsorption , COVID-19/complications , Critical Care/methods , Endotoxemia/etiology , Female , Heparin/administration & dosage , Humans , Male , Membranes, Artificial , Middle Aged , Polymyxin B/administration & dosage , Renal Replacement Therapy , Respiratory Distress Syndrome/etiology , Retrospective Studies , Treatment Outcome
9.
J Clin Apher ; 36(3): 313-321, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-978131

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.


Subject(s)
COVID-19/therapy , Hemoperfusion/instrumentation , Hemoperfusion/methods , Polymyxin B/chemistry , Polystyrenes/chemistry , Adult , Aged , Aged, 80 and over , Arteries/metabolism , Biomarkers/urine , Blood Gas Analysis , Cytokines/blood , Endothelium, Vascular/metabolism , Female , Hospitalization , Humans , Male , Middle Aged , Oxygen/metabolism , Respiration, Artificial , Retrospective Studies , Risk , beta 2-Microglobulin/urine
10.
Blood Purif ; 50(4-5): 575-577, 2021.
Article in English | MEDLINE | ID: covidwho-953495

ABSTRACT

We present the case of a patient who suffered from acute respiratory distress syndrome caused by pneumonia associated with COVID-19 and cytokine release syndrome. This patient received a high-volume hemofiltration plus adsorption, solving the hemodynamic deterioration, pulmonary infiltrates, and gas exchange. Our clinical case proposes that the extracorporeal therapies can have a role in the management of severe COVID-19.


Subject(s)
COVID-19/therapy , Critical Illness/therapy , Cytokine Release Syndrome/prevention & control , Hemofiltration , Hemoperfusion , SARS-CoV-2 , Acute Kidney Injury/etiology , Adrenal Cortex Hormones/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/diagnostic imaging , COVID-19/drug therapy , Combined Modality Therapy , Cytokine Release Syndrome/etiology , Cytokines/blood , Disease Progression , Drug Therapy, Combination , Hemoperfusion/methods , Humans , Hyperkalemia/etiology , Male , Middle Aged , Respiration, Artificial , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Vasoconstrictor Agents/therapeutic use
11.
Adv Chronic Kidney Dis ; 27(5): 377-382, 2020 09.
Article in English | MEDLINE | ID: covidwho-796111

ABSTRACT

Acute kidney injury is a common complication in hospitalized patients with coronavirus disease 2019. Similar to acute kidney injury associated with other conditions such as sepsis and cardiac surgery, morbidity and mortality are much higher in patients with coronavirus disease 2019 who develop acute kidney injury, especially in the intensive care unit. Management of coronavirus disease 2019-associated acute kidney injury with kidney replacement therapy should follow existing recommendations regarding modality, dose, and timing of initiation. However, patients with coronavirus disease 2019 are very hypercoagulable, and close vigilance to anticoagulation strategies is necessary to prevent circuit clotting. During situations of acute surge, where demand for kidney replacement therapy outweighs supplies, conservative measures have to be implemented to safely delay kidney replacement therapy. A collaborative effort and careful planning is needed to conserve dialysis supplies, to ensure that treatment can be safely delivered to every patient who will benefit for kidney replacement therapy.


Subject(s)
Acute Kidney Injury/therapy , Anticoagulants/therapeutic use , COVID-19/therapy , Renal Replacement Therapy/methods , Thrombophilia/drug therapy , COVID-19/blood , Catheterization, Central Venous , Central Venous Catheters , Citric Acid/therapeutic use , Continuous Renal Replacement Therapy/methods , Hemodialysis Solutions/supply & distribution , Hemoperfusion/methods , Heparin/therapeutic use , Humans , Hybrid Renal Replacement Therapy/methods , Intermittent Renal Replacement Therapy/methods , Kidneys, Artificial/supply & distribution , Partial Thromboplastin Time , Renal Replacement Therapy/instrumentation , SARS-CoV-2 , Surge Capacity , Thrombophilia/blood
12.
Intern Med ; 59(19): 2405-2408, 2020 Oct 01.
Article in English | MEDLINE | ID: covidwho-736583

ABSTRACT

An 83-year-old man was hospitalized for coronavirus disease 2019 (COVID-19) after a 10-day history of a persistent fever. Chest computed tomography showed extensive non-segmental ground glass opacity. Despite the initiation of lopinavir and ritonavir, respiratory failure progressed. Two days of polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) with adjunctive corticosteroid prevented his respiratory condition from worsening. For rapidly progressive COVID-19 cases, the early use of PMX-DHP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Hemoperfusion/methods , Pneumonia, Viral/complications , Polymyxin B/pharmacology , Respiratory Insufficiency/therapy , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , COVID-19 , Coronavirus Infections/epidemiology , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Respiration, Artificial/methods , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , SARS-CoV-2 , Tomography, X-Ray Computed
13.
Front Immunol ; 11: 1708, 2020.
Article in English | MEDLINE | ID: covidwho-688089

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the "cytokine storm" may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Interleukin-6/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Adrenal Cortex Hormones/therapeutic use , Animals , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Antimalarials/therapeutic use , Artesunate/therapeutic use , COVID-19 , Coronavirus Infections/virology , Hemoperfusion/methods , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/antagonists & inhibitors , Mice , Pandemics , Pneumonia, Viral/virology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , SARS-CoV-2
14.
Blood Purif ; 50(1): 28-34, 2021.
Article in English | MEDLINE | ID: covidwho-624949

ABSTRACT

In April 2020, the US Food and Drug Administration granted emergency use authorization for certain medical devices to be used in patients with coronavirus disease 2019 (CO-VID-19). This included extracorporeal blood purification devices. This narrative review will give a brief overview regarding some of the extracorporeal devices that could be used to treat COVID-19 patients, including the Seraph® 100 Microbind® Affinity Blood Filter, produced by ExThera Medical (Martinez, CA, USA), first licensed in the European Economic Area in 2019. The Seraph® 100 contains ultrahigh molecular weight polyethylene beads with end point-attached heparin and is approved for the reduction of pathogens from the bloodstream either as a single agent or as an adjunct to conventional anti-infective agents. Bacteria, viruses, fungi, and toxins have been shown to bind to the immobilized heparin in a similar way to the interaction with heparan sulfate on the cell surface. This binding is nonreversible and as such, the pathogens are removed from the bloodstream. In this review, we describe the pathophysiological basis and rationale for using heparin for pathogen removal from the blood as well as exploring the technology behind the adaptation of heparin to deprive it of its systemic anticoagulant activity. In addition, we summarize the in vitro data as well as the available preclinical testing and published clinical reports. Finally, we discuss the enormous potential of this technology in an era of increasing antibiotic resistance and high mortality associated with sepsis and consider the application of this as a possible treatment option for COVID-19.


Subject(s)
Anticoagulants/chemistry , Bacterial Infections/therapy , COVID-19/therapy , Hemoperfusion/methods , Heparin/chemistry , SARS-CoV-2/isolation & purification , Bacteria/isolation & purification , Bacterial Infections/blood , Binding Sites , COVID-19/blood , Humans
16.
Blood Purif ; 50(1): 17-27, 2021.
Article in English | MEDLINE | ID: covidwho-381787

ABSTRACT

Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems. In the absence of vaccines or direct therapy for COVID-19, extracorporeal therapies could represent an option to prevent organ failure and improve survival. The enormous demand in care for COVID-19 patients requires an immediate response from the scientific community. Thus, a detailed review of the available technology is provided by experts followed by a series of recommendation based on current experience and opinions, while waiting for generation of robust evidence from trials.


Subject(s)
COVID-19/therapy , Continuous Renal Replacement Therapy/methods , Critical Illness/therapy , Extracorporeal Membrane Oxygenation/methods , Hemoperfusion/methods , Multiple Organ Failure/therapy , COVID-19/blood , COVID-19/complications , Continuous Renal Replacement Therapy/instrumentation , Critical Illness/epidemiology , Cytokines/blood , Cytokines/isolation & purification , Equipment Design , Extracorporeal Membrane Oxygenation/instrumentation , Hemoperfusion/instrumentation , Humans , Multiple Organ Failure/blood , Multiple Organ Failure/etiology
17.
J Glob Antimicrob Resist ; 21: 340-341, 2020 06.
Article in English | MEDLINE | ID: covidwho-125519

ABSTRACT

Cytokine release syndrome is prevalent in severe cases of COVID-19. In this syndrome, an uncontrolled response of immune system occurs. Extracorporeal blood purification has been proven to effectively remove the released inflammatory cytokines. Here, we reported a successful case to represent our experience of extracorporeal blood purification in a patient with severe COVID-19.


Subject(s)
Coronavirus Infections/therapy , Hemoperfusion/methods , Pneumonia, Viral/therapy , Renal Replacement Therapy/methods , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/virology , Cytokines/blood , Humans , Interleukin-6/blood , Iran , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/virology , SARS-CoV-2
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