Hemoperfusion techniques using Jafron HA330 cartridge combined with BBraun Dialog+ dialysis machine in patient with coronavirus disease 2019 pneumonia and septic shock: a case report.

BACKGROUND: The use of hemoperfusion for cytokine removal and inflammatory mediators is increasingly intense, especially in coronavirus disease 2019 patients who are already known to the general public for having cytokine storms. However, we have known about these cytokine storms for a long time in the critical care world. One of the modalities to remove cytokines is to use filtration and adsorption techniques with continuous renal replacement therapy. The use of continuous renal replacement therapy is usually constrained by its very high cost compared with standard care, especially in Indonesia, where health costs are covered by national health insurance. In this case, we use hemodialysis and hemoperfusion, using a dialysis machine, which is more cost-effective and easy to use. CASE PRESENTATION: We used the Jafron HA330 cartridge, modified for the BBraun Dialog+ dialysis machine. This case report presents an 84-year-old Asian man with septic shock due to pneumonia, congestive heart failure, and acute chronic kidney disease accompanied by fluid overload. After undergoing hemodialysis and hemoperfusion separately, there was a gradual and significant clinical improvement. Clinical indicators, including the vasopressor inotropic score and infection markers, should all be considered when deciding whether to begin hemodialysis and hemoperfusion. CONCLUSION: In general, using hemoperfusion to treat septic shock patients can reduce the length of stay in the intensive care unit, and morbidity and mortality.

Rationale for sequential extracorporeal therapy (SET) in sepsis.

Sepsis and septic shock remain drivers for morbidity and mortality in critical illness. The clinical picture of patients presenting with these syndromes evolves rapidly and may be characterised by: (a) microbial host invasion, (b) establishment of an infection focus, (c) opsonisation of bacterial products (e.g. lipopolysaccharide), (d) recognition of pathogens resulting in an immune response, (e) cellular and humoral effects of circulating pathogen and pathogen products, (f) immunodysregulation and endocrine effects of cytokines, (g) endothelial and organ damage, and (h) organ crosstalk and multiple organ dysfunction. Each step may be a potential target for a specific therapeutic approach. At various stages, extracorporeal therapies may target circulating molecules for removal. In sequence, we could consider: (a) pathogen removal from the circulation with affinity binders and cartridges (specific), (b) circulating endotoxin removal by haemoperfusion with polymyxin B adsorbers (specific), (c) cytokine removal by haemoperfusion with sorbent cartridges or adsorbing membranes (non-specific), (d) extracorporeal organ support with different techniques for respiratory and cardiac support (CO2 removal or extracorporeal membrane oxygenation), and renal support (haemofiltration, haemodialysis, or ultrafiltration). The sequence of events and the use of different techniques at different points for specific targets will likely require trials with endpoints other than mortality. Instead, the primary objectives should be to achieve the desired action by using extracorporeal therapy at a specific point.

Effectiveness of hemoperfusion (HP) in hemodialysis (HD) patients with Covid-19 infection.

INTRODUCTION: The aims of this study are to observe the clinical course of all patients affected by infection with SARS-CoV-2 undergoing HD focusing on the impact of HP. METHODS: Patients were divided into Group A: HD sessions with HP and Group B: patients without HP. We registered all the data regarding patients' clinical course. RESULTS: 13 patients have been enrolled in group A. 9 patients were discharged from the hospital after 43 days (range: 35-56). 30 days was the mean hospitalization stay for the deceased. We did not observe any side effects with HP cartridges. 9 patients did not receive HP during their hospitalization. For those who represented as symptomatic, 8 out of 9 patients died after 6 days of hospitalization (range: 1-14), 2 of them in ICU. CONCLUSION: HP seems to be a helpful, safe and quite efficient tool in the battle against Covid-19 in HD patients.

Interim analysis of the COSA (COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter) registry.

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.

The role of artificial cells in the fight against COVID-19: deliver vaccine, hemoperfusion removes toxic cytokines, nanobiotherapeutics lower free radicals and pCO2 and replenish blood supply.

This review concentrates on how artificial cells can contribute to helping patients with COVID-19. Artificial cells have led to mRNA vaccines with more improvements to come. Excessive cytokines in severe COVID-19 can damage organs leading to death. Artificial cell-based collodion macroporous activated charcoal adsorbent can effectively remove middle molecular weight range molecules in patients. A novel hemoperfusion device based on collodion membrane macroporous synthetic resin effectively removes cytokines and recovery in COVID-19 patients. This has been approved as an emergency treatment for COVID-19 in China, Europe, and Canada. A recent nanobiotherapeutic containing haemoglobin and up to six times the concentration of red blood cell enzymes: catalase, superoxide dismutase and carbonic anhydrase. In an animal study, this can effectively lower the damaging increase in free radicals and the removal of increased tissue pCO2. This can also help as blood substitute for the severe and critical problem of COVID-19 pandemic donor blood supply crisis.KEY MESSAGESCOVID-19 and its variants have resulted in major pandemics, severe sicknesses, and deaths around the world. COVID-19 and its variants has only started less than 3 years ago, and it is even more recently that we know more about its mechanisms, requirements, prevention, and treatment. This being the case, this is the first review on the present status and future perspectives of the use of the principle of artificial cells for COVID-19 related to vaccines, treatment, and critical donor blood supply shortage.

Hemoperfusion as an Adjuvant Therapy in Maintenance Hemodialysis Patients with Severe COVID-19: A Single Centre Experience.

Mortality rate among maintenance hemodialysis (HD) patients with COVID-19 is alarmingly high. In Fatmawati General Hospital, most of HD patients with COVID-19 presented with acute respiratory distress syndrome (ARDS). Hemoperfusion (HP) is a blood purification therapy used to remove cytokines and inflammatory mediators to prevent ARDS worsening and organ failure. We report 6 cases of COVID-19 in maintenance HD patients. HP and HD were performed in two consecutive days when patient developed early ARDS as indicated by inflammatory markers elevation. HP and HD were conducted by using resin-containing cartridge and high-flux dialyzer, respectively, for 4 hours. Improvements in CRP levels, PaO2/FiO2 ratios, and chest X-rays were observed after 2 sessions of HP in most of our patients. Based on our clinical experience, the timing of HP delivery is critical and should be undertaken in the early phase of ARDS, but larger studies are still needed.

Can charcoal hemoperfusion treatment be an option for pediatric MIS-C patients? A single-center experience in a tertiary pediatric intensive care unit.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a hyper-inflammatory disorder that develops following SARS-CoV-2 infection and has clinical signs that overlap with Kawasaki disease. Immunomodulatory treatments can be used in these patients. One of the alternative treatments reported in the literature is hemoperfusion therapy. In this study, we aim to evaluate our experience of charcoal hemoperfusion therapy in children admitted and followed up with a diagnosis of MIS-C at our Pediatric Intensive Care Unit (PICU). MATERIAL AND METHODS: We performed a retrospective evaluation of children diagnosed with MIS-C and children treated with charcoal hemoperfusion who are admitted to our PICU. RESULTS: Among 49 MIS-C patients, hemoperfusion therapy was performed on 14 patients. Duration of hospitalization, duration of invasive/non-invasive ventilation, VIS, OFI, PRISM 3 scores, and mortality rates were significantly higher in the charcoal hemoperfusion group before treatment. In patients who did not respond to conventional therapies, we observed a statistically significant decrease in the need for inotrope and invasive mechanical ventilation support and statistically significant improvements in clinical indicators after hemoperfusion therapy. DISCUSSION: In our study, we observed a significant clinical and laboratory improvement by charcoal hemoperfusion in our MIS-C patients who had a severe clinical course and multiple organ failure. CONCLUSION: In our opinion, this study is the first report regarding the use of charcoal hemoperfusion therapy in MIS-C patients, and the choice of charcoal hemoperfusion as an initial or rescue therapy is needed to be investigated in large patient groups both in children and adults who are diagnosed with COVID-19 and MIS-C.

Literature Review of Hemadsorption Therapy in Severe COVID-19 Cases: a Narrative Review.

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.

The Efficacy of Early Additional Hemoperfusion Therapy for Severe COVID-19 Patients: A Prospective Cohort Study.

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.

The early start of hemoperfusion decreases the mortality rate among severe COVID-19 patients: A preliminary study.

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.

Hemoperfusion and blood purification strategies in patients with COVID-19: A systematic review.

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.

Application of extracorporeal therapies in critically ill COVID-19 patients.

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.

Two Patients With Severe COVID Pneumonia Treated With the Seraph-100 Microbind Affinity Blood Filter.

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.

Therapeutic Rationale for Endotoxin Removal with Polymyxin B Immobilized Fiber Column (PMX) for Septic Shock.

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.

Hemoperfusion with CytoSorb® in Critically Ill COVID-19 Patients.

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.