Hemoperfusion with CytoSorb as Adjuvant Therapy in Critically Ill Patients with SARS-CoV2 Pneumonia

Background: Several pro- and anti-inflammatory cytokines involved in COVID-19 and it is reasonable to speculate that their removal from blood might limit organ damage. Hemoperfusion with CytoSorb is a technique developed to adsorb molecules in the middle molecular weight range (up to 55 kDa). Studies in vitro and in vivo have shown that HP is highly effective in clearing blood from a number of cytokines. Method(s): We report a case series of 9 consecutive COVID-patients admitted to our COVID Intensive Care Unit (ICU). Five of them were treated with HP using CytoSorb (T), due to the heavy emergency overload it was impossible to deliver blood purification in the other 4 patients (C), who were also considered as potential candidates by the attending medical team. All patients had pneumonia and respiratory failure requiring continuous positive airway pressure. Different antibacterial prophylaxes, antiviral, and anti-inflammatory therapies including steroids were delivered. Result(s): Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. CRP decreased in both groups, but to a greater extent after HP. Lymphocytopenia worsened in control patient but not in treated patient after HP. Procalcitonin increased in 2 of the not treated patients. In all survived patients (n = 4) HP reduced pro-inflammatory cytokines, as IL-6, TNF-alpha, and IL-8. Notably, a striking effect was observed on IL-6 levels that at the end of the second session were decreased by a 40% than before the first treatment. Serum levels of IL-8 and TNF-alpha were lowered within normal range. In all patients the treatment was safe and there were no complications. Conclusion(s): Our study suggests a potential efficacy of HP in an early phase of viral infection not only for improving survival in the treated patients but also by the remodeling treatment-associated cytokine levels.

A Successful Treatment of a Critically Patient with SARS-CoV2

Background: The role of inflammatory cytokines is known in the pathogenesis of organ damage and is also confirmed in the context of COVID-19 disease. The modulation of the cytokine storm seems to determine endothelial protection, which can translate into a reduction of the "capillary leak syndrome", and, consequently, in a better control of the formation of edema and pulmonary infiltrates. CytoSorb stands in this context as a cartridge capable of adsorbing cytokines and allowing a better clinical course. Case Report: A 69 years-old woman with a history of arterial hypertension, diabetes mellitus and CKD, was admitted to ICU for SARS Cov 2 related critical illness staged with chest CT, blood gas analysis and PCR. At the admission, the patient presented with ubiquitous interstitial pneumonia, PaO2 60 mmHg with 90% Airvo2 and PCR 36.67. Therefore, in order to remove inflammatory cytokines, the patient underwent hemoperfusion treatment with the CytoSorb adsorbent cartridge. Method(s): The protocol used is approved by the FDA for the treatment of covid patients and consists of the use of 4 cartridges 12h, 12h, 24h, 24h with measurement for each cycle of PCR, PaO2 and chest CT control. Result(s): During the hemoperfusion whit CytoSorb, respiratory failure improved until the patient was discharged from the ICU on the tenth day, with oxygen support via simple facial mask. Below the progressive values of the PCR, PaO2 and the chest CT control on the twelfth day. Conclusion(s): The hemoperfusion treatment with the CytoSorb adsorbent cartridge proved to be a valid adjuvant therapy in determining a better clinical course both in terms of the need for invasive mechanical ventilation and survival.

Evaluation of clinical features and laboratory findings in critical intensive care unit patients with severe coronavirus disease-19 who underwent extracorporeal cytokine adsorption.

AIM: To evaluate the inflammatory parameters and oxygenation in severe coronavirus disease-19 patients who underwent extracorporeal cytokine adsorption (CA). METHODS: Patients who underwent extracorporeal CA for cytokine storm were included in the study. The changes in oxygenation, laboratory parameters, and mortality rates were investigated. RESULTS: Thirty-six patients were included in the study. The hemoglobin, thrombocyte, and C-reactive protein (CRP) decreased, and PaO2 /FiO2 ratio increased (p < 0.001; p < 0.01; p < 0.001; p = 0.04, respectively). Twelve (33.3%) patients received a single session, 24 (66.6%) received 2 or more sessions. CRP and fibrinogen levels decreased, and PaO2 /FIO2 ratio increased in the single session group (p = 0.04; p = 0.04; p = 0.01, respectively). In the multi-session group, the hemoglobin, platelet, procalcitonin, and CRP levels decreased, and PaO2 /FIO2 ratio increased (p < 0.01; p = 0.02; p = 0.02; p < 0.01; p = 0.01, respectively). Day 15, 30, and 90 mortality rates were 61.1%, 83.3%, and 88.9%. CONCLUSION: CA with hemoperfusion reduced CRP and improved oxygenation; however, mortality rates were high.

EXTRACORPOREAL THERAPY IN CRITICALLY ILL PATIENTS WITH COVID-19: A SINGLE-CENTER EXPERIENCE.

Aim To assess the safety and efficacy of extracorporeal therapy in patients with COVID-19. The study included 27 patients aged 67+/-9.7 [min 38, max 87] years with a laboratory-confirmed SARS-CoV-2 and bilateral polysegmental pneumonia, various concomitant chronic diseases who were admitted to Intensive Care Unit and received extracorporeal therapies. All patients had the mean NEWS score of 6.9+/-2.7 [min 4, max 9] and the mean SOFA score of 8.1+/-3.1 [min 3, max 16] at admission Methods to the ICU. 19 patients (70.4%) had severe lung lesions over 75% according to the chest CT scans. 48 extracorporeal therapies were performed using the Multifiltrate (Fresenius Medical Care, Germany) and Aquarius (Nikkiso Aquarius RCA, Great Britain) medical devices. Indications for extracorporeal therapy initiation included cytokine storm associated with acute respiratory distress syndrome and septic shock. Generally, each patient received at least one extracorporeal therapy. 11 patients underwent 2 to 6 sessions. Isolated plasma separation and hemoperfusion helped to reduce vasopressor / cardiotonic support, slightly improved ventilation parameters, with a significant, but not long-term decrease in the levels of inflammation markers. Combining different modalities of extracorporeal therapy that provide rapid elimination of agents, controlled temperature response and hydration, maintaining Results homeostasis and detoxification, appeared to be most optimal. Extracorporeal therapy did not improve the volume of lung parenchyma or lung parenchyma damage. However, 19 (70.4%) patients who received extracorporeal therapy transitioned from mechanical ventilation to spontaneous breathing, whereas 8 (29.6%) patients had severe lung lesions (over 75%) according to the repeated chest CT scans. The mean length of stay in the ICU among survivors was 9+/-3.5 [min 4, max 22]. The 28-day mortality and in-hospital mortality rate was 25.9% (7). Prolonged extracorporeal therapy in patients with SARS-Cov-2 has demonstrated Conclusion efficacy in relieving organ dysfunctions and shock states, but did not significantly affect the remaining lung parenchyma damage.Copyright © 2022 University of Latvia. All Rights Reserved.

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.

Comparison of outcomes and costs of extracorporeal blood purification therapies in critically ill COVID-19 patients.

INTRODUCTION: Plasmapheresis and hemoperfusion are used against cytokine release syndrome in COVID-19. This study aims to compare their outcomes, costs, and side-effects. METHODS: Survival, costs and side-effects were compared in intensive care unit (ICU) patients receiving plasmapheresis (n = 49), hemoperfusion (n = 20), or none (n = 107), followed until death or discharge. RESULTS: Plasmapheresis survival time was higher than hemoperfusion or controls (HR = 0.764, p = 0.397 and HR = 0.483, p = 0.002, respectively), although the latter diminished after controlling for age and disease severity (p = 0.979). There was no significant difference in ICU costs for plasmapheresis and hemoperfusion (p = 0.738) while both costed more than controls (both p < 0.001). Hypocalcemia and thrombocytopenia incidence did not differ between two groups (p = 0.124 and p = 0.389, respectively) while being higher than controls in plasmapheresis (both p < 0.001) and hemoperfusion (p < 0.001 and p = 0.056, respectively). CONCLUSION: Plasmapheresis and hemoperfusion do not differ significantly in patient survival, ICU costs and side-effects with a higher incidence of hypocalcemia and thrombocytopenia compared witcontrols.

Predictors of Clinical Efficacy of Cytokine Hemoadsorption in COVID-19 (Clinical Trial).

Aim of the study. To evaluate the value of predictors of hemoadsorption clinical efficacy in patients with COVID-19. Materials and methods. This study analyzed the results of treatment of 62 patients with severe COVID-19 in the intensive care unit using selective hemoadsorption of cytokines. All patients with severe COVID-19 were admitted to the intensive care unit within 14 days from the disease onset were subdivided into two groups. Group 1 patients (n=32) received on a top of standard treatment the hemoperfusion (HP) procedure for 4 hours, for 2-3 days in a row, using a cytokine sorption column composed of mesoporous styrene-divinilbenzen copolymer matrix. Group 2 patients were not subjected to extracorporeal blood purification. All patients received IL-6 inhibitors at a baseline in accordance to the temporary guidelines. We evaluated factors of unfavorable outcomes by analyzing changes in biochemical markers of systemic inflammatory response and mortality rates in patients of both groups. Results. Initiation of HP later than 10 days from NCI onset (P < 0.001), length of stay in the ICU, extent of lung damage (P = 0.036) and the SOFA (Sequential Organ Failure Assessment) score (P = 0.009) were the most powerful predictors of unfavorable outcome. Levels of systemic inflammatory response markers (in-terleukin-6, CRP, D-dimer) in both groups did not significantly affect the survival rates and length of hospital stay (P > 0.05). HP group demonstrated better survival (P < 0.05). Mean hospital stay was 31 and 27 days, ICU stay - 11 and 8 days for Groups 1 and 2, respectively (P < 0.05). Conclusion. Treatment of severe COVID-19 patients with HP using novel domestic hemosorbent composed of styrene-divinilbenzen copolymer matrix resulted in decrease in CRP levels on the first day after application and, with early onset, contributed to a significant increase in survival and decreased hospital and ICU stay. Additional studies are warranted to clarify the optimal timing of the initiation of HP in severe COVID-19 patients.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

Predictors of Clinical Efficacy of Cytokine Hemoadsorption in COVID-19 (Clinical Trial).

Aim of the study. To evaluate the value of predictors of hemoadsorption clinical efficacy in patients with COVID-19. Materials and methods. This study analyzed the results of treatment of 62 patients with severe COVID-19 in the intensive care unit using selective hemoadsorption of cytokines. All patients with severe COVID-19 were admitted to the intensive care unit within 14 days from the disease onset were subdivided into two groups. Group 1 patients (n=32) received on a top of standard treatment the hemoperfusion (HP) procedure for 4 hours, for 2-3 days in a row, using a cytokine sorption column composed of mesoporous styrene-divinilbenzen copolymer matrix. Group 2 patients were not subjected to extracorporeal blood purification. All patients received IL-6 inhibitors at a baseline in accordance to the temporary guidelines. We evaluated factors of unfavorable outcomes by analyzing changes in biochemical markers of systemic inflammatory response and mortality rates in patients of both groups. Results. Initiation of HP later than 10 days from NCI onset (P < 0.001), length of stay in the ICU, extent of lung damage (P = 0.036) and the SOFA (Sequential Organ Failure Assessment) score (P = 0.009) were the most powerful predictors of unfavorable outcome. Levels of systemic inflammatory response markers (in-terleukin-6, CRP, D-dimer) in both groups did not significantly affect the survival rates and length of hospital stay (P > 0.05). HP group demonstrated better survival (P < 0.05). Mean hospital stay was 31 and 27 days, ICU stay - 11 and 8 days for Groups 1 and 2, respectively (P < 0.05). Conclusion. Treatment of severe COVID-19 patients with HP using novel domestic hemosorbent composed of styrene-divinilbenzen copolymer matrix resulted in decrease in CRP levels on the first day after application and, with early onset, contributed to a significant increase in survival and decreased hospital and ICU stay. Additional studies are warranted to clarify the optimal timing of the initiation of HP in severe COVID-19 patients.Copyright © 2023, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

The Relationship of Hyponatremia with Il-6 and Implications on Clinical Outcomes in Covid-19 Patients Admitted at University Santo Tomas Hospital, January to August 2021

Introduction: COVID-19 is a droplet-transmitted infection with clinical manifestation ranging from mild disease to cytokine storm. The cytokine storm is an exaggerated response of the human body in which excessive amounts of inflammatory markers are released leading to multiple organ failure. In COVID-19, the most common electrolyte disorder noted is hyponatremia. Hyponatremia results from an increase in cytokines including IL-6 can result in the release of anti-diuretic hormone causing a decrease in serum sodium. Hyponatremic patients were observed to have increased risk for ICU admission, mechanical ventilation and mortality as compared to normonatremia. The inflammatory markers including serum ferritin, procalcitonin, IL-6, HsCRP, LDH, and D-dimer have been imperative as prognostic markers to help guide healthcare workers in the classification of severity, thereby guiding management. This study aims to investigate the association between serum sodium and serum IL-6 and aims to establish the role of serum sodium as an alternative cost-effective prognostic marker for COVID-19. Method(s): This is a retrospective cohort study done at the University of Santo Tomas Hospital via chart review of all confirmed COVID-19 patients admitted from January to August 2021. Data gathered included patient's age, gender, pertinent co-morbidities, day of illness on arrival, serum Na, PF ratio, chest radiograph, IL-6 levels on admission. The outcome of each case was recorded: oxygen supplementation, need for hemoperfusion, need for tocilizumab, COVID classification, days until clinical recovery, discharged, or expired. Corrected serum was used to account for effect of serum glucose on serum sodium. Serum sodium and IL-6 levels were compared to check the relationship between the two. Hyponatremia was studied in line with the poor outcomes. COVID-19 patients admitted at the COVID ward of USTH, January to August 2021 was the target population of the study. Those excluded were patients with chronic kidney disease patients, chronic hyponatremia, malignancy, uncontrolled thyroid disease, liver cirrhosis, on diuretics, with gastrointestinal losses and incomplete records. [Formula presented] Results: Of the 322 admitted COVID-19 patients, 154 were included with 89 (58%) having poor outcomes. Hyponatremia was seen in 60 (38.9%) of the population while 48 (53.93%) had poor outcomes. Serum sodium and IL-6 have an inverse relationship is not statistically significant. Patients with hyponatremia were 4.46 times more likely to require high oxygen support, 4.16 times more likely to need hemoperfusion, and 60.71% times more likely to have ICU admission. Hyponatremia was shown to have a 94.12% likelihood need for tocilizumab, 3.87 times more likely to result in severe or critical COVID-19 and 3.78 times more likely to expire. Overall, hyponatremia was 5.17 times more likely to have poor clinical outcome in comparison to normonatremia. Conclusion(s): Serum sodium cannot replace serum IL-6 as an inflammatory marker, but could be considered as a potential prognostic marker for COVID-19 when inflammatory markers are not available. COVID-19 patients with hyponatremia have a higher predisposition to increased disease severity. Including serum sodium in scoring systems could help signal to the health care providers that a more aggressive treatment approach would be indicated, thus aiding physicians in managing patients more effectively. No conflict of interestCopyright © 2023

Clinical Outcome of Covid-19 Severe-Critical Patients after Hemoperfusion (Ha 330) at the Victoriano Luna Medical Center: A Retrospective Cohort Study

Introduction: In December 2019, a novel coronavirus, COVID-19, emerged in Wuhan, posing a severe threat to global health. Pro-inflammatory cytokines are frequently found in COVID-19 patients, which is believed to be a critical factor in the pathogenicity of the disease. Similar to other outbreaks caused by new viral agents, an approved treatment has not yet been introduced, and treatment protocols presented in scientific evidence are all symptomatic and supportive. Despite the use of various drugs, including antivirals, innovative treatment approaches are urgently needed to enhance the prognosis of these patients. One of the treatment approaches that can be taken to reduce these cytokines is hemoperfusion. The association of increased cytokines releases with the severity of COVID-19 disease and the effect of hemoperfusion in the removal of these cytokines prompted this study to determine the survival and hospitalization outcomes of COVID 19 Severe-Critical patients after hemoperfusion admitted at the Armed Forces of the Philippines Health Service, Victoriano Luna Medical Center. Method(s): This is a single-center retrospective cohort study conducted at Armed Forces of the Philippines Health Service Command, Victoriano Luna Medical Center among COVID-19 Severe-Critical from November 2020 to November 2021. Eligible patients were classified into hemoperfusion and non-hemoperfusion groups. Demographic characteristics and clinical outcomes were identified. Laboratory parameters were collected and compared before and after treatment between the two groups. Result(s): The total number of patients identified as COVID Severe - Critical admitted at Victoriano Luna Medical Center from November 2020 to November 2021 was 342. Due to the unavailability and incompleteness of several charts, there are only 68 patients who are included in the study who underwent hemoperfusion and 286 patients included under the standard regimen (non-hemoperfusion). The majority of the patients are males (55.9% for HP, 52.3% for non-HP) with an average age of 60-69 years old in both groups. The most common comorbidity noted was hypertension (70% for HP;62% for non-HP) in both groups. Among the inflammatory markers measured, Pao2, CRP, and LDH were noted to have improved after the fourth session of hemoperfusion. Regression of pneumonia on chest x-ray was also observed among the HP group. The average length of hospital stay for the HP group is 26.69 days which is greater than the non-HP group (19.12 days). Mortality is 45% higher in the HP group compared to the non-HP group (21.5%). However, there is no association noted between mortality and patient group. Conclusion(s): This study showed the clinical outcome of patients who underwent hemoperfusion versus the standard regimen. Most were hypertensive men in their 60s with severe to critical COVID-19 disease. Among the laboratory measures, there was noted improvement in the partial oxygen pressure (PaO2), C-reactive protein (CRP), lactate dehydrogenase (LDH), and pneumonia on chest x-ray among patients who underwent hemoperfusion. Even still, mortality rates are high, and hospital stays are lengthy. No conflict of interestCopyright © 2023

Clinical Outcomes of Hemoperfusion Using Ha330 Filter among Patients with Severe and Critical Covid-19 at the University of Santo Tomas Hospital: A One-Year Retrospective Study

Introduction: COVID-19 became a global pandemic in 2020 and currently, there is no definitive treatment. Severe and critically ill COVID-19 patients are admitted due to respiratory illness and failure leading to multiple-organ dysfunction syndrome. Cytokine release syndrome (CRS) is prevalent among these patients. Hemoperfusion is a form of extracorporeal therapy that effectively removes the inflammatory cytokines that lead to lung damage. This study was conducted to determine the clinical outcomes of patients diagnosed with Severe and Critical COVID-19 who underwent hemoperfusion at the University and Santo Tomas Hospital. Method(s): This retrospective study included 135 severe and critical COVID-19 patients who underwent hemoperfusion using an HA330 cartridge. Demographic, clinical data, and outcomes were described. APACHE II score, Hemoglobin, platelet count, leukocytes, neutrophils, lymphocytes, serum creatinine, inflammatory markers such as serum ferritin, hs-CRP, IL-6, LDH, procalcitonin, D-dimer, PaO2/FiO2 (PF) ratio were compared pre and post hemoperfusion (HP) among those survivors and non-survivors. The effects of the timing of hemoperfusion on different clinical parameters and outcomes were described. Result(s): The most common cause of death is respiratory (20%). There were 98 patients (73%) who survived. Mortality rates were elevated among chronic kidney disease and cancer patients. APACHE II score was lower post hemoperfusion compared to baseline levels among survivors. After 4 sessions of hemoperfusion, hemoglobin and platelet counts were lower among non-survivors. WBC levels were increased for all patients. Neutrophils increased compared to baseline among those who expired. Lymphocytes were decreased compared to baseline among non-survivors. There is no significant change in creatinine levels compared to baseline. Post HP ferritin, LDH, and D-dimer were elevated among non-survivors. Among survivors, hs-CRP and procalcitonin were lower compared to baseline. Post HP ferritin and D-dimer increased among survivors. IL-6 levels showed no significant difference post-HP from baseline but we reported higher levels among non-survivors versus survivors. PF ratio was higher post hemoperfusion among patients who survived compared to those who died. The effect of timing of hemoperfusion was divided into 14 days versus more than 14 days of illness. The APACHE II score for those who underwent hemoperfusion within 14 days showed a lower score. There was no significant difference in the baseline levels of hematologic counts, inflammatory markers, and PF ratio among those who underwent hemoperfusion beyond 14 days. For those who underwent hemoperfusion within 14 days, hemoglobin, hs-CRP, IL-6, and procalcitonin were lower compared to baseline while neutrophils, ferritin, d-dimer, and PF ration had increased levels. Most patients who underwent hemoperfusion within 14 days of illness required high flow O2 supplementation than an invasive mechanical ventilator. Conclusion(s): Hemoperfusion results in lower APACHE II score, hemoglobin, HsCRP, and procalcitonin levels. There was no significant difference from baseline clinical parameters among those who underwent hemoperfusion beyond 14 days of illness. Those who underwent hemoperfusion within 14 days of illness required less invasive mechanical O2 support. This was also submitted for the ISN Frontiers, New Delhi but was not presented. No conflict of interestCopyright © 2023

Association of Hemoperfusion Disease Progression among Patients with Severe-to-Critical Covid-19

Introduction: Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) which can lead to respiratory failure, acute respiratory distress syndrome (ARDS), pneumonia, and sepsis1. The symptoms of severe COVID-19 usually occur after a few days when viral replication is decreasing and excessive inflammation in the lung alveoli are present. Subsequently, excessive inflammation led to abnormalities in gas exchange, abnormalities in ventilation, and abnormalities in blood perfusion in the lungs2. Severe disease also has the characteristics present in Cytokine Release Syndrome (CRS) such as high fever, and elevated levels of ferritin and C-reactive protein2. Hemoperfusion has been offered to patients with severe COVID-19 who continue to have disease progression and increased inflammatory markers despite maximizing medical therapy. Our main objective is to determine the association of hemoperfusion with the development of disease progression among patients with at least severe COVID-19 in Asian Hospital and Medical Center from March 2020 to March 2021. Method(s): This is a retrospective cohort of patients aged-19 and older with a diagnosis of at least severe COVID-19 who were grouped according to whether they received hemoperfusion or not. These patients were monitored throughout their hospital course for the development of disease progression (i.e., mortality or need for mechanical ventilation). Multivariate analysis was used to determine the association of hemoperfusion with disease progression. Result(s): A total of 267 patients were included in the study, 128 (47.9%) underwent hemoperfusion, and 139 (52.1%) did not. Those who underwent hemoperfusion were older, had more co-morbidities (hypertension, diabetes, and chronic kidney disease), and had more severe disease. Disease progression occurred in 127 patients (47.5%), which was higher in those who underwent hemoperfusion (94 patients). On multivariate analysis, hemoperfusion was significantly associated with the need for intubation (RR 11.94, CI 5.3-26.8;p<0.0001), in-hospital mortality (RR 4.56, CI 2.2-9.4, p<0.0001), and the composite of disease progression (RR 7.44, CI 3.9-14.2, p<0.0001). Thrombocytopenia and hypocalcemia were also significantly more common among those who received hemoperfusion (p<0.0001). [Formula presented] [Formula presented] Conclusion(s): Our cohort showed that hemoperfusion was associated with the development of disease progression and more adverse events. However, those who received hemoperfusion had more co-morbidities and had more severe disease at the onset, which may explain our findings. Based on this study, hemoperfusion could not be recommended in the routine management of patients with at least severe COVID-19;however, a randomized controlled trial is highly recommended to verify our findings. No conflict of interestCopyright © 2023

Effect of Hemoperfusion on the Clinical Outcome of Severe and Critical Covid-19 Patients Admitted at the University of Santo Tomas Hospital: An Analytical Cohort Study

Introduction: Severe sepsis is a life-threatening end organ dysfunction resulting from dysregulated host response to infection and poses a significant burden to healthcare systems worldwide. Since the advent of CoVID-19, cytokine release syndrome has also been attributed to clinical deterioration presenting as acute respiratory distress syndrome and acute kidney injury of infected individuals. Objective(s): To determine the clinical outcome of Severe and Critical COVID-19 patients who underwent hemoperfusion compared with patients who did not undergo hemoperfusion. Method(s): This study entailed a retrospective cohort analysis of patients aged >= 18 and < 90 years old admitted at University of Santo Tomas Hospital who were diagnosed with Severe or Critical COVID-19. Subjects were grouped between those who underwent hemoperfusion (HP group) using HA 330 cartridge and those who did not undergo the procedure (non-HP). Demographic and clinical data collected for both groups included age, sex, comorbidities present, time to initiation of hemoperfusion, total hemoperfusion time, use of other medications specifically: immunomodulator and anti-viral drugs, antibiotics and steroid, length of hospital stay and in-hospital mortality. Mean arterial pressure, cardiac rate, oxygen saturation, arterial blood gas, complete blood count, oxygen requirement, inotropic score, serum creatinine, urine output, lactate dehydrogenase (LDH), ferritin, high sensitivity C-reactive protein (HsCRP), Interleukin-6 values and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were compared from baseline and after 4 sessions of hemoperfusion for the HP group. The clinical outcomes: length of hospital stay, in-hospital mortality and time to off high flow nasal cannula (HFNC) between two groups were also compared. Result(s): A total of 98 cases were included, 49 subjects underwent hemoperfusion using HA 330 and 49 patients did not undergo hemoperfusion. Demographic data is similar between both groups. Baseline clinical data between Hemoperfusion and non-Hemoperfusion group did not show statistical difference. However, Baseline LDH, HsCRP, Ferritin, IL-6, PF ratio and APACHE II score were statistically different between two groups. Effect on Disease Severity Length of hospital stay and time to off HFNC was shorter in the non-HP group vs the HP group, median of 13 days vs 18 days (p-value 0.003) and 107 hours vs 222 hours (p- value <0.001), respectively. There is also no significant difference in in-hospital mortality between two groups. [Formula presented] [Formula presented] [Formula presented] Conclusion(s): This retrospective study did not show survival benefit with the use of hemoperfusion. Undergoing hemoperfusion did not show a significant effect on changes in disease severity as represented by no significant difference seen in APACHE II score, PF ratio, acute kidney injury, length of hospital stay and in-hospital mortality. Hemoperfusion also has no significant effect in terms of decreasing the values of inflammatory markers LDH, ferritin, and IL-6. A large, multi-center, randomized clinical trial is warranted to truly determine the clinical benefit of hemoperfusion not only in severe to critical COVID-19 but also in severe sepsis and conditions that trigger systemic inflammatory response and cytokine storm. *This abstract was also submitted for the ISN Frontiers:Infections and the Kidneys congress. No conflict of interestCopyright © 2023

Comparative Study of Clinical Outcomes of Severe and Critical COVID-19 Patients With and Without Hemoperfusion Admitted in a Referral Hospital

Introduction: COVID-19 has been a global problem since 2020, and is challenging to manage, leading to countless deaths worldwide. Severe cases are due to cytokine release syndrome resulted in acute respiratory distress syndrome. Hemoperfusion has been proposed as a means of removing cytokines from the circulation, theoretically improving survival. Objective(s): This study compared the clinical outcomes of hemoperfusion among severe and critical COVID-19 patients admitted in a COVID-19 referral hospital. Method(s): This is a retrospective cohort study involving hospital records of severe and critical COVID-19 adult patients. Patients were grouped according to severity and hemoperfusion status. Statistical analysis was done using Chi-square and Kaplan Meier survival analysis, through SPSS ver 22. Result(s): There were 435 patients included in the study, of which 155 were patients without hemoperfusion, and 280 with hemoperfusion. There was significant reduction in inflammatory markers (CRP, LDH, Ferritin & D-dimer with pvalue <0.01) post-hemoperfusion for both severe critical groups. There was a higher survival probability of 45% and 20% on the 10th and 20th day of admission respectively among severe COVID-19 with hemoperfusion. Severe COVID-19 patient with hemoperfusion had higher extubation rate of 34.4% than those without (9.5%). Among patients on Day 1-6 illness with hemoperfusion, they had higher survival probability of 80% than those who had it later. Conclusion(s): Hemoperfusion was associated with higher survival outcome among severe COVID-19 patients than those without. Apt timing of initiation of hemoperfusion can improve survival.

Ultraefficiently Calming Cytokine Storm Using Ti3C2T x MXene.

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 Ti3C2T x 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.

Comparison of the Effects of Continuous Renal Replacement Therapy and Hemodialysis on Complications, Vital Signs, and Laboratory Parameters in Patients with COVID-19

Introduction: Evidence shows that continuous renal replacement therapy (CRRT) and hemodialysis may be effective in the treatment of Coronavirus disease-2019 (COVID-19). This study aimed to compare the effects of CRRT and hemodialysis on complications, vital signs, and laboratory parameters in patients with COVID-19. Material(s) and Method(s): This cross-sectional study was performed on 113 patients with COVID-19 who underwent hemoperfusion in Kosar Hospital of Semnan city (Iran) between 2020 and 2021. The patients were divided into two groups, the CRRT hemoperfusion group (n=49) and the hemodialysis group (n=64). A checklist was used for collecting data, which included demographic variables, history of underlying diseases, vital signs, laboratory parameters, complications, and various outcomes, which were extracted through interviews with patients or companions and in medical records. IBM Statistical Package for the Social Sciences Statistics for Windows version 26 was used for data analysis. Result(s): The time from hemoperfusion to hospital discharge (3.84+/-4.51 vs. 5.92+/-4.16 day), duration of intubation (0.33+/-0.94 vs. 1.84+/-3.42), death after hemoperfusion (64.06 vs. 26.5%), situational instability (21.9 vs. 8.2%), and death during hemoperfusion (14.1 vs. 0%) were significantly lower in the CRRT group than in the hemodialysis group (p<0.05). In the repeated-measures analysis of variance (ANOVA) test, the two groups demonstrated a statistically significant difference in lactate dehydrogenase, alkaline phosphatase, white blood cell count, and C-reactive protein at different time points;thus, the mean of these variables was significantly lower after hemoperfusion in the CRRT group than in the hemodialysis group (p<0.05). Conclusion(s): Continuous renal replacement therapy hemoperfusion can be effective in the recovery process of patients with COVID-19 because the length of hospital stay, intubation period, situational instability, and mortality during and after hemoperfusion are less than those of hemodialysis. © Copyright 2022 by the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey Mediterranean Journal of Infection, Microbes and Antimicrobials published by Galenos Yayinevi.

Hemoperfusion that was popular during the COVID-19 pandemic: A case series

The medical world has been seeking solutions in solving the Coronavirus disease 2019 (COVID-19) outbreak since 2019. Amongst several alter-natives, hemoperfusion therapy has been reported to be beneficial for alleviating symptoms and reducing mortality in severely ill COVID-19 patients. Hemoperfusion is a process of filtering blood to eliminate toxins and inflammatory factors from the body. This case series aims to high-light the unexpected adverse clinical and labora-tory outcomes in the majority of COVID-19 patients treated with hemoperfusion in our hospi-tal. We included fifteen patients admitted to the Intensive Care Unit (ICU) with moderate-to-se-vere COVID-19 between August and December 2020 and were all given two to four sessions of hemoperfusion using the MG150 cartridge. All ten men and five women showed no improve-ment in their neutrophil-lymphocyte ratio (NLR), ferritin, D-dimer, and C-reactive protein (CRP) values after the hemoperfusion regiments, both survivors and non-survivors. In addition, eleven out of twelve patients with respiratory failure who were then intubated resulted in death. Based on our findings and previous evi-dence, we recommended only performing hemoperfusion for investigational instead of therapeutic purposes due to its poorly under-stood pathophysiology in COVID-19. We also recommended further research regarding the us-age of hemoperfusion in COVID-19 patients, es-pecially in the matter of determining the best time to start the therapy.Copyright © 2023, The Indonesian Foundation of Critical Care Medicine. All rights reserved.

Effect of Hemadsorption Therapy in Critically Ill Patients with COVID-19 (CYTOCOV-19): A Prospective Randomized Controlled Pilot Trial.

INTRODUCTION: Immunomodulatory therapies have shown beneficial effects in patients with severe COVID-19. Patients with hypercytokinemia might benefit from the removal of inflammatory mediators via hemadsorption. METHODS: Single-center prospective randomized trial at the University Medical Center Hamburg-Eppendorf (Germany). Patients with confirmed COVID-19, refractory shock (norepinephrine ≥0.2 µg/kg/min to maintain a mean arterial pressure ≥65 mm Hg), interleukin-6 (IL-6) ≥500 ng/L, and an indication for renal replacement therapy or extracorporeal membrane oxygenation were included. Patients received either hemadsorption therapy (HT) or standard medical therapy (SMT). For HT, a CytoSorb® adsorber was used for up to 5 days and was replaced every 18-24 h. The primary endpoint was sustained hemodynamic improvement (norepinephrine ≤0.05 µg/kg/min ≥24 h). RESULTS: Of 242 screened patients, 24 were randomized and assigned to either HT (N = 12) or SMT (N = 12). Both groups had similar severity as assessed by SAPS II (median 75 points HT group vs. 79 SMT group, p = 0.590) and SOFA (17 vs. 16, p = 0.551). Median IL-6 levels were 2,269 (IQR 948-3,679) and 3,747 (1,301-5,415) ng/L in the HT and SMT groups at baseline, respectively (p = 0.378). Shock resolution (primary endpoint) was reached in 33% (4/12) versus 17% (2/12) in the HT and SMT groups, respectively (p = 0.640). Twenty-eight-day mortality was 58% (7/12) in the HT compared to 67% (8/12) in the SMT group (p = 1.0). During the treatment period of 5 days, 6/12 (50%) of the SMT patients died, in contrast to 1/12 (8%) in the HT group. CONCLUSION: HT was associated with a non-significant trend toward clinical improvement within the intervention period. In selected patients, HT might be an option for stabilization before transfer and further therapeutic decisions. This finding warrants further investigation in larger trials.

Microbead-based extracorporeal immuno-affinity virus capture: a feasibility study to address the SARS-CoV-2 pandemic.

In this paper, we report on the utilization of micro-technology based tools to fight viral infections. Inspired by various hemoperfusion and immune-affinity capture systems, a blood virus depletion device has been developed that offers highly efficient capture and removal of the targeted virus from the circulation, thus decreasing virus load. Single-domain antibodies against the Wuhan (VHH-72) virus strain produced by recombinant DNA technology were immobilized on the surface of glass micro-beads, which were then utilized as stationary phase. For feasibility testing, the virus suspension was flown through the prototype immune-affinity device that captured the viruses and the filtered media left the column. The feasibility test of the proposed technology was performed in a Biosafety Level 4 classified laboratory using the Wuhan SARS-CoV-2 strain. The laboratory scale device actually captured 120,000 virus particles from the culture media circulation proving the feasibility of the suggested technology. This performance has an estimated capture ability of 15 million virus particles by using the therapeutic size column design, representing three times over-engineering with the assumption of 5 million genomic virus copies in an average viremic patient. Our results suggested that this new therapeutic virus capture device could significantly lower virus load thus preventing the development of more severe COVID-19 cases and consequently reducing mortality rate.

Outcome and Complications of Hemoperfusion in Patients with COVID-19 in Intensive Care Unit: A Cross-Sectional Study.

BACKGROUND & OBJECTIVE: The use of the hemoperfusion method is recommended treating cytokine storms and reduce complications in patients with COVID-19. The side effects of this treatment are not known; therefore, this study was performed to determine the final outcome and complications of hemoperfusion in patients with COVID-19 hospitalized in ICU. METHODS: In this retrospective cross-sectional study, all patients with severe COVID-19 without any comorbidities or organ failure who underwent hemoperfusion treatment in ICU at Kosar Hospital in Semnan, Iran, during March - November 2021 were included. The clinical data and short-term complications up to 10 days after hemoperfusion and the final outcome were extracted from medical files. RESULTS: The mean age of 40 patients with severe COVID-19 undergoing hemoperfusion was 57.5±15.9 years. Most (24, 60%) patients were male. The time interval from hospitalization to hemoperfusion and the time interval between hemoperfusion and final outcome was 4.85 days and 8.30 days, respectively. Arrhythmia, bleeding, thrombocytopenia, and coagulation disorders were the most common short-term complications of hemoperfusion in patients with COVID-19, respectively. Most complications occurred on the second and third days after hemoperfusion. Mortality occurred in 20 (50 %) patients with severe COVID-19 undergoing hemoperfusion in ICU. CONCLUSION: It seems that the short-term complications and deaths due to hemoperfusion are relatively high in patients with COVID-19 admitted to the ICU. Further studies are recommended.