The Seraph 100® Microbind Affinity Blood Filter Does Not Alter Levels of Circulating or Mucosal Antibodies in Critical COVID-19 Patients.
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ABSTRACT:
SUBMITTER: Conner TL
PROVIDER: S-EPMC11348046 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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The Seraph 100<sup>®</sup> Microbind Affinity Blood Filter Does Not Alter Levels of Circulating or Mucosal Antibodies in Critical COVID-19 Patients.
Conner Tonia L TL Vir Pooja P Laing Eric D ED Stewart Ian J IJ Mitre Edward E Pratt Kathleen P KP
Antibodies (Basel, Switzerland) 20240806 3
PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100<sup>®</sup> Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated beads that can bind to, and reduce levels of, some circulating pathogens and inflammatory molecules. This study evaluated whether treatment with the Seraph 100 affected circulating and mucosal a ...[more]
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Project description:Abstract Background and Aims The COVID-19 pandemic has serious impact on health and economics worldwide. Despite the recent advent of SARS-Cov-2 vaccines, treatment options are needed, yet pharmacologic interventions remain limited. Several extracorporeal treatments are currently explored concerning their potential to improve the clinical course and outcome of critically ill patients with COVID-19. The Seraph® 100 Microbind® Affinity adsorber (Exthera Medical, CA, USA) has recently been introduced for the elimination of several pathogens from the blood and an emergency authorization in patients with COVID-19 was granted by the FDA. Bacteria, viruses (including the SARS-CoV-2 spike glycoprotein), fungi and toxins have been shown to bind to the immobilized heparin on the ultra-high molecular weight polyethylene beads of the device in a similar way to the interaction with heparan sulfate on the cell-surface and are thereby removed from the bloodstream. Here we report the interim analysis of the COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter (COSA) registry. The goal of the registry is to gather data regarding the safety and efficacy of the Seraph® 100 in the treatment of COVID-19 patients. Method Participating sites were advised to insert patient data of COVID-19 patients, treated with the Seraph® 100, during their hospital stay into the COSA registry (ClinicalTrials.gov Identifier: NCT04361500). A total of 66 items were asked in a web-based platform. Results Until January 2021, 33 patients with 39 treatment sessions form six different hospitals were reported to the register (seven female, median age 61 years, Table 1). The patients were treated between March and December 2020. Eleven patients with a hospital admission between March and August and 22 between September and December 2020. The Seraph® 100 treatment was initiated 9 days after symptom onset, without any difference between survivors and non-survivors. Overall, a mortality of 27% was reported. Serious comorbidities (as preadmission immunosuppressive therapy, lung fibrosis or CKD5T) were reported in all of the non-survivors. Invasive ventilation was needed in 67% of these patients when Seraph treatment was initiated. A non-significant trend towards higher Ferritin levels in non-survivors (2000 (1963 – 8326) vs. 989 (644 – 2000), p=0.09) was reported. All treatments were well tolerated, three clotting events were reported. Conclusion Viral SARS-CoV-2 RNA is frequently (up to 78%) seen in the blood of critically ill COVID-19 patients and correlates with the severity of the disease. The Seraph® 100 can bind to viral spike protein, proinflammatory cytokines may be reduced by the device and hemodynamic stabilization has been reported during the Seraph®100 treatment of COVID-19 patients. Platelets can be hyperactivated in association with SARS-CoV-2 proteins and thus presumably trigger the hypercoagulation and thrombosis. In this context, the removal of SARS-CoV-2 proteins to prevent hyperactivated platelets appears to be a sensible approach. All reported deaths were associated with serious preexisting comorbidities, immunosuppression, dialysis dependent renal failure, or a combination of these factors. Hence, Seraph® 100 treatment may be most beneficial in COVID-19 courses of patients without multi organ failure. More clinical data is needed to describe possible benefits of the Seraph®100 in the treatment of COVID-19 patients.
| S-EPMC8194996 | biostudies-literature
Project description:IntroductionExtracorporeal blood purification systems represent a promising alternative for treatment of blood stream infections with multiresistant bacteria.ObjectivesThe aim of this study was to analyse the binding activity of S. aureus to Seraph affinity filters based on heparin coated beads and to identify effectors influencing this binding activity.ResultsTo test the binding activity, we used gfp-expressing S. aureus Newman strains inoculated either in 0.9% NaCl or in blood plasma and determined the number of unbound bacteria by FACS analyses after passing through Seraph affinity filters. The binding activity of S. aureus was clearly impaired in human plasma: while a percent removal of 42% was observed in 0.9% NaCl (p-value 0.0472) using Seraph mini columns, a percent removal of only 10% was achieved in human plasma (p-value 0.0934). The different composition of surface proteins in S. aureus caused by the loss of SarA, SigB, Lgt, and SaeS had no significant influence on its binding activity. In a clinically relevant approach using the Seraph® 100 Microbind® Affinity Filter and 1000 ml of human blood plasma from four different donors, the duration of treatment was shown to have a critical effect on the rate of bacterial reduction. Within the first four hours, the number of bacteria decreased continuously and the reduction in bacteria reached statistical significance after two hours of treatment (percentage reduction 64%, p-value 0.01165). The final reduction after four hours of treatment was close to 90% and is dependent on donor. The capacity of Seraph® 100 for S. aureus in human plasma was approximately 5 x 108 cells.ConclusionsThe Seraph affinity filter, based on heparin-coated beads, is a highly efficient method for reducing S. aureus in human blood plasma, with efficiency dependent on blood plasma composition and treatment duration.
| S-EPMC10022791 | biostudies-literature
Project description:BackgroundThe 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.MethodsTwelve 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.ResultsOverall, 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%.ConclusionsThe 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.
| S-EPMC8689741 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) pandemic has a serious impact on health and economics worldwide. Even though the majority of patients present with moderate and mild symptoms, yet a considerable portion of patients need to be treated in the intensive care unit. Aside from dexamethasone, there is no established pharmacological therapy. Moreover, some of the currently tested drugs are contraindicated for special patient populations like remdesivir for patients with severely impaired renal function. On this background, several extracorporeal treatments are currently explored concerning their potential to improve the clinical course and outcome of critically ill patients with COVID-19. Here, we report the use of the Seraph 100 Microbind Affinity filter, which is licensed in the European Union for the removal of pathogens. Authorization for emergency use in patients with COVID-19 admitted to the intensive care unit with confirmed or imminent respiratory failure was granted by the U.S. Food and Drug Administration on April 17, 2020. A 53-year-old Caucasian male with a severe COVID-19 infection was treated with a Seraph Microbind Affinity filter hemoperfusion after clinical deterioration and commencement of mechanical ventilation. The 70-minute treatment at a blood flow of 200 mL/minute was well tolerated, and the patient was hemodynamically stable. The hemoperfusion reduced D-dimers dramatically. This case report suggests that the use of Seraph 100 Microbind Affinity filter hemoperfusion might have positive effects on the clinical course of critically ill patients with COVID-19. However, future prospective collection of data ideally in randomized trials will have to confirm whether the use of Seraph 100 Microbind Affinity filter hemoperfusion is an option of the treatment for COVID-19.
| S-EPMC8046512 | biostudies-literature
Project description:The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19.DesignRetrospective cohort study.SettingNine participating ICUs.PatientsCOVID-19 patients treated with Seraph 100 (n = 53) and control patients matched by study site (n = 53).InterventionTreatment with Seraph 100.Measurements and main resultsAt baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41-65) compared with controls (median age, 64 yr; IQR, 56-69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0-3) compared with the control group (3; IQR, 2-4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9-17) compared with controls (16; IQR, 12-21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded.ConclusionsAlthough this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines.
| S-EPMC9049035 | biostudies-literature
Project description:BackgroundBacterial burden as well as duration of bacteremia influence the outcome of patients with bloodstream infections. Promptly decreasing bacterial load in the blood by using extracorporeal devices in addition to anti-infective therapy has recently been explored. Preclinical studies with the Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100), which consists of heparin that is covalently bound to polymer beads, have demonstrated an effective binding of bacteria and viruses. Pathogens adhere to the heparin coated polymer beads in the adsorber as they would normally do to heparan sulfate on cell surfaces. Using this biomimetic principle, the Seraph® 100 could help to decrease bacterial burden in vivo.MethodsThis first in human, prospective, multicenter, non-randomized interventional study included patients with blood culture positive bloodstream infection and the need for kidney replacement therapy as an adjunctive treatment for bloodstream infections. We performed a single four-hour hemoperfusion treatment with the Seraph® 100 in conjunction with a dialysis procedure. Post procedure follow up was 14 days.ResultsFifteen hemodialysis patients (3F/12 M, age 74.0 [68.0-78.5] years, dialysis vintage 28.0 [11.0-45.0] months) were enrolled. Seraph® 100 treatment started 66.4 [45.7-80.6] hours after the initial positive blood culture was drawn. During the treatment with the Seraph® 100 with a median blood flow of 285 [225-300] ml/min no device or treatment related adverse events were reported. Blood pressure and heart rate remained stable while peripheral oxygen saturation improved during the treatment from 98.0 [92.5-98.0] to 99.0 [98.0-99.5] %; p = 0.0184. Four patients still had positive blood culture at the start of Seraph® 100 treatment. In one patient blood cultures turned negative during treatment. The time to positivity (TTP) was increased between inflow and outflow blood cultures by 36 [- 7.2 to 96.3] minutes. However, overall TTP increase was not statistical significant.ConclusionsSeraph® 100 treatment was well tolerated. Adding Seraph® 100 to antibiotics early in the course of bacteremia might result in a faster resolution of bloodstream infections, which has to be evaluated in further studies.Trail registrationClinicalTrials.gov Identifier: NCT02914132 , first posted September 26, 2016.
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Project description:IMGT®, the international ImMunoGeneTics® information system founded in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS), marked the advent of immunoinformatics, a new science at the interface between immunogenetics and bioinformatics. For the first time, the immunoglobulin (IG) or antibody and T cell receptor (TR) genes were officially recognized as 'genes' as well as were conventional genes. This major breakthrough has allowed the entry, in genomic databases, of the IG and TR variable (V), diversity (D) and joining (J) genes and alleles of Homo sapiens and of other jawed vertebrate species, based on the CLASSIFICATION axiom. The second major breakthrough has been the IMGT unique numbering and the IMGT Collier de Perles for the V and constant (C) domains of the IG and TR and other proteins of the IG superfamily (IgSF), based on the NUMEROTATION axiom. IMGT-ONTOLOGY axioms and concepts bridge genes, sequences, structures and functions, between biological and computational spheres in the IMGT® system (Web resources, databases and tools). They provide the IMGT Scientific chart rules to identify, to describe and to analyse the IG complex molecular data, the huge diversity of repertoires, the genetic (alleles, allotypes, CNV) polymorphisms, the IG dual function (paratope/epitope, effector properties), the antibody humanization and engineering.
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Project description:Fenofibrate (FE) has been shown to markedly reduce the progression of diabetic retinopathy and age-related macular degeneration in clinical trials and animal models. Owing to the limited aqueous solubility of FE, it may hamper ocular bioavailability and result in low efficiency to treat such diseases. To enhance the solubility of FE, water-soluble FE/cyclodextrin (CD) complex formation was determined by a phase-solubility technique. Randomly methylated-β-CD (RMβCD) exhibited the best solubility and the highest complexation efficiency (CE) for FE. Additionally, water-soluble polymers (i.e., hydroxypropyl methyl cellulose and polyvinyl alcohol [PVA]) enhanced the solubility of FE/RMβCD complexes. Solid- and solution-state characterizations were performed to elucidate and confirm the formation of inclusion FE/RMβCD complex. FE-loaded Eudragit® nanoparticle (EuNP) dispersions and suspensions were developed. The physicochemical properties (i.e., pH, osmolality, viscosity, particle size, size distribution, and zeta potential) were within acceptable ranges. Moreover, in vitro mucoadhesion, in vitro release, and in vitro permeation studies revealed that the FE-loaded EuNP eye drop suspensions had excellent mucoadhesive properties and sustained FE release. The hemolytic activity, hen's egg test on chorioallantoic membrane assay, and in vitro cytotoxicity test showed that the FE formulations had low hemolytic activity, were cytocompatible, and were moderately irritable to the eyes. In conclusion, PVA-stabilized FE/RMβCD-loaded EuNP eye drop suspensions were successfully developed, warranting further in vivo testing.
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