Severe forms of the coronavirus disease 2019 (COVID-19) can progress to sepsis-like complications accompanied by "cytokine storm" for which the most effective treatment has not yet been established. Our study describes the results of CytoSorb hemoadsorption in COVID-19 patients treated on the intensive care unit (ICU). In this retrospective study, 26 patients with COVID-19 and acute respiratory distress syndrome (ARDS) were treated with hemoadsorption therapy. Pre-, and post-treatment values (clinical and laboratory) were compared. Data are expressed as mean (confidence intervals, CI), or median [interquartile ranges, IQR], as appropriate. Patients received 2 hemoadsorption treatments. This resulted in a significant decrease in norepinephrine requirements, and inflammatory marker plasma concentrations (procalcitonin, C-reactive protein, ferritin) when comparing pre versus post treatment levels. The PaO2 /FiO2 and overall organ function (ie, Sequential Organ Failure Assessment-SOFA score) also improved significantly. Patients stayed on the ICU for 9 days and 21 of them survived. To the best of our knowledge, this is one of the largest case series to date reporting early experiences on extracorporeal hemoadsorption therapy in SARS-CoV-2 positive patients with hyperinflammation and moderate ARDS. Treatment proved to be effective, technically feasible and well-tolerated.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/aor.14024

Blood purification with CytoSorb in critically ill COVID-19 patients: A case series of 26 patients.


 Background : A dysregulated inflammatory response, known as “cytokine storm”, plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). There is a subgroup of patients who develop a hyperinflammatory response with severe respiratory failure and organ dysfunction with high mortality. Identifying these patients is outstanding as they could benefit from specific therapies, such as cytokine removal by hemoadsorption. Methods: Single-center, observational and prospective study of critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure and hypercytokinemia. All patients received cytokine hemoadsorption using Cytosorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate prone response, and hypercytokinemia. Results : A total of 343 patients were admitted to the ICU due to SARS-Cov-2 infection between March 3, 2020, to June 22, 2020. Of these, six patients [5 (83.3%) men; mean age 57 (10.5) years; SOFA 5 (1.4); mean Acute Physiology And Chronic Health Evaluation (APACHE) II score 19.5 (6)] underwent hemoadsorption with Cytosorb®. All patients fulfilled the Berlin criteria for severe acute respiratory distress syndrome (ARDS), underwent prone positioning, and were on mechanical ventilation for 15.2 (7.2) days. One session of 16 (9.0) hours duration was performed. IL-6 levels were significantly reduced [(pre- hemoadsorption levels 17.367 (4.539– 22.532) pg/ml; post-hemoadsorption levels 2.403 (917 – 3.724) pg/ml, p = 0.043], and improvements in oxygenation were observed [pre-hemoadsorption PaO 2 /FiO 2 ratio was 103 (18.4), post- hemoadsorption PaO2/FiO2 ratio was 222 (20.9), p = 0.029]. We documented the clinical improvement and rapid reversal of organ dysfunction [pre-hemoadsorption Sequential Organ Failure Assessment (SOFA) score 9 (4.7); post- hemoadsorption SOFA score 7.7 (5.4), p = 0.046]. Inflammatory markers (C-reactive protein, D-dimer, and ferritin) also improved significantly. Mean ICU stay was 17.2 (8.0) days. ICU and in-hospital mortality was 33.7%. Conclusions : In our cohort, patients with SARS-CoV-2 pneumonia and severe acute respiratory failure and hypercytokinemia who received cytokine hemoadsorption, an important reduction in IL-6 levels and improvements in oxygenation and SOFA score were observed.

/pdf/cytokine-hemoadsorption-as-rescue-therapy-for-critically-ill-m6zggt78qs.pdf

Cytokine Hemoadsorption As Rescue Therapy for Critically Ill Patients with SARS-CoV-2 Pneumonia with Severe Respiratory Failure and Hypercytokinemia

On March 11, 2020, the World Health Organization (WHO) officially declared the outbreak caused by the new coronavirus (SARS-CoV-2) a pandemic. The rapid spread of the disease surprised the scientific and medical community. Based on the latest reports, news, and scientific articles published, there is no doubt that the coronavirus has overloaded health systems globally. Practical actions against the recent emergence and rapid expansion of the SARS-CoV-2 require the development and use of tools for discovering new molecular anti-SARS-CoV-2 targets. Thus, this review presents bioinformatics and molecular modeling strategies that aim to assist in the discovery of potential anti-SARS-CoV-2 agents. Besides, we reviewed the relationship between SARS-CoV-2 and innate immunity, since understanding the structures involved in this infection can contribute to the development of new therapeutic targets. Bioinformatics is a technology that assists researchers in coping with diseases by investigating genetic sequencing and seeking structural models of potential molecular targets present in SARS-CoV2. The details provided in this review provide future points of consideration in the field of virology and medical sciences that will contribute to clarifying potential therapeutic targets for anti-SARS-CoV-2 and for understanding the molecular mechanisms responsible for the pathogenesis and virulence of SARS-CoV-2.

The New Coronavirus (SARS-CoV-2): A Comprehensive Review on Immunity and the Application of Bioinformatics and Molecular Modeling to the Discovery of Potential Anti-SARS-CoV-2 Agents.

The current pandemic of coronavirus disease 2019 (COVID-19) spotlighted the vulnerability of patients with chronic kidney disease stage 5 on maintenance hemodialysis (HD) to the viral infection. Social distancing is the most effective preventive measure to reduce the risk of infection. Nonetheless, the necessity to frequently reach the dialysis center and the inherent social gathering both impede social distancing and also self-quarantine for infected individuals. A baseline hyperinflammatory state driven by factors such as the retention of uremic toxins afflicts these patients. Concomitantly, a condition of relative immunosuppression is also attributed to similar factors. The use of high-flux (HF) dialyzers for HD is the standard of care. However, with HF membranes, the removal of large middle molecules is scant. Medium cutoff (MCO) dialyzers are a new class of membranes that allow substantial removal of large middle molecules with negligible albumin losses. Recent trials confirmed long-term safety and long-term sustained reduction in the concentration of large uremic toxins with MCO dialyzers. Herein, we discuss the rationale for applying MCO membranes in COVID-19 patients and its possible immunoadjuvant effects that could mitigate the burden of COVID-19 infection in dialysis patients. We also discuss the direct cytopathic effect of the virus on renal tissue and extracorporeal blood purification techniques that can prevent kidney damage or reduce acute kidney injury progression.

/pdf/rationale-for-medium-cutoff-membranes-in-covid-19-patients-358h2a5baj.pdf

Rationale for Medium Cutoff Membranes in COVID-19 Patients Requiring Renal Replacement Therapy.

In late 2019, a novel betacoronavirus, later termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in patients with an unknown respiratory illness in Wuhan, China. SARS-CoV-2 and the disease caused by the novel coronavirus, coronavirus disease 2019 (COVID-19), spread rapidly and resulted in the World Health Organization declaring a pandemic in March 2020. In a minority of patients infected with SARS-CoV-2, severe illness develops characterized by a dysregulated immune response, acute respiratory distress syndrome, and multisystem organ failure. Despite the development of antiviral and multiple immunomodulatory therapies, outcomes of severe illness remain poor. In response, the Food and Drug Administration in the United States authorized the emergency use of several extracorporeal blood purification (EBP) devices for critically ill patients with COVID-19. Extracorporeal blood purification devices target various aspects of the host response to infection to reduce immune dysregulation. This review highlights the underlying technology, currently available literature on use in critically ill COVID-19 patients, and future studies involving four EBP platforms: 1) oXiris filter, 2) CytoSorb filter, 3) Seraph 100 Microbind blood affinity filter, and 4) the Spectra Optia Apheresis System with the Depuro D2000 Adsorption Cartridge. 

A Review of Extracorporeal Blood Purification Techniques for the Treatment of Critically Ill Coronavirus Disease 2019 Patients

The SARS-COV-2-19-associated respiratory involvement is caused by the massive release of inflammatory cytokines ultimately leading to interstitial pneumonia and acute respiratory distress syndrome (ARDS). In the absence of an effective antiviral treatment, a reasonable causal approach could be constituted by the neutralization of these substances. The authors describe the clinical course of a patient with SARS-COV-2-19 interstitial pneumonia treated with the combination of an anti-interleukin 6 (IL-6) agent (tocilizumab) and hemoadsorption (HA). This combination was used to abate the surge of inflammatory mediators leading to the lung damage. Blood levels of IL-6 and C-reactive protein (CRP) were measured before the initiation of the treatment and in the following 3 days. At the end of the treatment, the values of IL-6 and CRP decreased from 1,040 to 415 pg/mL and from 229 to 59 mg/L, respectively. The gas exchanges and the chest imaging rapidly improved, and the patient was extubated 10 days later. The combination of tocilizumab and HA could be valuable in the treatment of SARS-COV-2-19-associated pneumonia and ARDS that are caused by the release of inflammatory mediators.

/pdf/the-combined-use-of-tocilizumab-and-hemoadsorption-in-a-573jnig220.pdf

The Combined Use of Tocilizumab and Hemoadsorption in a Patient with SARS-COV-2-19-Associated Pneumonia: A Case Report.

The mismanagement of plastics is associated with high levels of waste and release into the environment, where they can persist for long times due to the low degradation rate. Photocatalytic methods, based on the action of Reactive Oxygen Species (ROS) generated by semiconductor materials, are promising eco-friendly and low-cost process for the plastics degradation. Here, eco-designed Humic Acids-doped/ZnO nanoparticles were synthesized via solvothermal route and tested as photocatalysts for the degradation of linear low-density polyethylene (LLDPE) and polylactic acid (PLA) thin films, under UVA/light irradiation. LLDPE is one of the most common commercial polymers widely used in packaging field wherein PLA is also broadly used to replace conventional plastics. The combination of diagnostic techniques (TEM/SEM, XRD, TGA/DSC, ATR/FTIR, EPR and DRUV) allowed to define the structure-property-function relationships of the hybrid nanomaterials and to monitor the chemical, structural and morphological changes occurring on the polymeric films as a consequence of the photodegradation. Experimental results demonstrated the validity of this eco-sustainable approach to realize hybrid photocatalysts with enhanced ROS-generating ability suitable for an improved photo-oxidation of plastics in aqueous environment. • A bottom-up solvothermal synthesis leads to humic acid-doped ZnO nanoparticles. • The supramolecular design of nanohybrids valorizes the biowaste-derived molecules. • An improved ROS-generating ability occurs in aqueous medium under UVA irradiation. • Humic acid-doped ZnO nanoparticles enhance the photo-oxidation of LLDPE and PLA films. • Photodegradation results in deep furrows on the surface of plastic films. 

Paola Amato

Papers

The Combined Use of Tocilizumab and Hemoadsorption in a Patient with SARS-COV-2-19-Associated Pneumonia: A Case Report.

Eco-sustainable design of Humic Acids-doped ZnO nanoparticles for UVA/light photocatalytic degradation of LLDPE and PLA plastics.

Copper indium sulfide quantum dots in photocatalysis.