Cytokine adsorption during ECMO for COVID-19-related ARDS.
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ABSTRACT:
SUBMITTER: Shekar K
PROVIDER: S-EPMC8121532 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Systemic inflammation is a key characteristic of sepsis but also also in non-infectious conditions such as post-cardiac arrest syndrome. Cytokine adsorption and extracorporeal membrane oxygenation are emerging therapies applied in these critically ill patients, but the experience with their concurrent use is limited. We evaluated cytokine adsorption in critically ill patients requiring support with either veno-venous (vv) or veno-arterial (va) extracorporeal membrane oxygenation (ECMO) support and hypothesized that adsorber incorporation into the ECMO circuit was technically feasible and not associated with imminent risk. We analyzed data from the first six cases of a prospective single-center registry of patients undergoing veno-venous (vv) or veno-arterial (va) ECMO therapy. While in most published cases cytokine adsorbers were inserted into a hemofiltration circuit, we directly incorporated the adsorber into the ECMO circuit without interruption of continuous ECMO support. We observed no relevant side effects attributable to cytokine adsorption. Thirty-day mortality was 83% (predicted mortality 87%), indicating that the decision for adding cytokine adsorption may have been considered as an ultima ratio decision in severe cases with poor prognosis. Vasopressor or inotrope use, lactate level, and fluid balance did not change significantly when comparing pre- vs. post-cytokine adsorption values. Interestingly, the real-time course of the mentioned three surrogate parameters remained unaltered in all but two cases, regardless of cytokine removal. Beneficial effects of cytokine adsorption are plausible in two va-ECMO-treated patient, where increasing lactate began to drop after initiation of cytokine adsorption. Taken together, these data suggest that incorporation of cytokine adsorption into the management of critically ill patients requiring continued ECMO support is feasible and easy to handle. Whether cytokine removal improves clinical outcome in ECMO-treated patients should now be investigated in randomized controlled trials.
| S-EPMC6593298 | biostudies-literature
Project description:Many coronavirus disease 2019 (COVID-19) patients demonstrate lethal respiratory complications caused by cytokine release syndrome (CRS). Multiple cytokines have been implicated in CRS, but levels of tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) have not been previously measured in this setting. In this study, we observed significantly elevated serum LIGHT levels in hospitalized COVID-19 patients compared to healthy age- and gender-matched control patients. The assay detected bioavailable LIGHT unbound to the inhibitor Decoy receptor-3 (DcR3). Bioavailable LIGHT levels were elevated in patients both on and off ventilatory support, with a trend toward higher levels in patients requiring mechanical ventilation. In hospitalized patients over the age of 60, who exhibited a mortality rate of 82%, LIGHT levels were significantly higher (P = 0.0209) in those who died than in survivors. As previously reported, interleukin 6 (IL-6) levels were also elevated in these patients, with significantly (P = 0.0076) higher levels observed in patients who died than in survivors, paralleling the LIGHT levels. Although attempts to block IL-6 binding to its receptor have shown limited success in COVID-19 CRS, neutralization of LIGHT may prove to be more effective owing to its more central role in regulating antiviral immune responses. The findings presented here demonstrate that LIGHT is a cytokine which may play an important role in COVID-19 patients presenting with acute respiratory distress syndrome (ARDS) and CRS and suggest that LIGHT neutralization may be beneficial to COVID-19 patients.
| S-EPMC7426176 | biostudies-literature
Project description: Not available
| S-EPMC8209893 | biostudies-literature
Project description:BackgroundECMO is a particularly scarce resource during the COVID-19 pandemic. Its allocation involves ethical considerations that may be different to usual times. There is limited pre-pandemic literature on the ethical factors that ECMO physicians consider during ECMO allocation. During the pandemic, there has been relatively little professional guidance specifically relating to ethics and ECMO allocation; although there has been active ethical debate about allocation of other critical care resources. We report the results of a small international exploratory survey of ECMO clinicians' views on different patient factors in ECMO decision-making prior to and during the COVID-19 pandemic. We then outline current ethical decision procedures and recommendations for rationing life-sustaining treatment during the COVID-19 pandemic, and examine the extent to which current guidelines for ECMO allocation (and reported practice) adhere to these ethical guidelines and recommendations.MethodsAn online survey was performed with responses recorded between mid May and mid August 2020. Participants (n = 48) were sourced from the ECMOCard study group-an international group of experts (n = 120) taking part in a prospective international study of ECMO and intensive care for patients during the COVID-19 pandemic. The survey compared the extent to which certain ethical factors involved in ECMO resource allocation were considered prior to and during the pandemic.ResultsWhen initiating ECMO during the pandemic, compared to usual times, participants reported giving more ethical weight to the benefit of ECMO to other patients not yet admitted as opposed to those already receiving ECMO, (p < 0.001). If a full unit were referred a good candidate for ECMO, participants were more likely during the pandemic to consider discontinuing ECMO from a current patient with low chance of survival (53% during pandemic vs. 33% prior p = 0.002). If the clinical team recommends that ECMO should cease, but family do not agree, the majority of participants indicated that they would continue treatment, both in usual circumstances (67%) and during the pandemic (56%).ConclusionsWe found differences during the COVID-19 pandemic in prioritisation of several ethical factors in the context of ECMO allocation. The ethical principles prioritised by survey participants were largely consistent with ECMO allocation guidelines, current ethical decision procedures and recommendations for allocation of life-sustaining treatment during the COVID-19 pandemic.
| S-EPMC8169422 | biostudies-literature
Project description:BackgroundSince March 2020, health care systems were importantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, with some patients presenting severe acute respiratory distress syndrome (ARDS), requiring extra-corporeal membrane oxygenation (ECMO). We designed an ambispective observational cohort study including all consecutive adult patients admitted to 5 different ICUs from a university hospital. The main objective was to identify the risk factors of severe COVID-19 ARDS patients supported by ECMO associated with 90-day survival.ResultsBetween March 1st and November 30th 2020, 76 patients with severe COVID-19 ARDS were supported by ECMO. Median (interquartile range IQR) duration of mechanical ventilation (MV) prior to ECMO was of 6 (3-10) days. At ECMO initiation, patients had a median PaO2:FiO2 of 71 mmHg (IQR 62-81), median PaCO2 of 58 mmHg (IQR 51-66) and a median arterial pH of 7.33 (IQR 7.25-7.38). Forty-five patients (59%) were weaned from ECMO. Twenty-eight day, 60-day and 90-day survival rates were, respectively, 92, 62 and 51%. In multivariate logistic regression analysis, with 2 models, one with the RESP score and one with the PRESERVE score, we found that higher BMI was associated with higher 90-day survival [odds ratio (OR): 0.775 (0.644-0.934), p = 0.007) and 0.631 (0.462-0.862), respectively]. Younger age was also associated with 90-day survival in both models [OR: 1.1354 (1.004-1.285), p = 0.044 and 1.187 (1.035-1.362), p = 0.014 respectively]. Obese patients were ventilated with higher PEEP than non-obese patients and presented slightly higher respiratory system compliance.ConclusionIn this ambispective observational cohort of COVID-19 severe ARDS supported by ECMO, obesity was an independent factor associated with improved survival at 90-day.
| S-EPMC8591429 | biostudies-literature
Project description:The novel coronavirus (COVID-19) has become a global pandemic outbreak. Patients with COVID-19 are prone to progress to acute respiratory distress syndrome (ARDS), and even severe ARDS with ineffective mechanical ventilation, and an extremely high mortality. Extracorporeal membrane oxygenation (ECMO) provides effective respiratory support and saves time for the treatment of severe COVID-19. The present study reports that a 31-year-old pregnant female infected by COVID-19, who suffered from fever, dyspnea, and rapid ARDS. The patient's pulmonary function gradually recovered by combining early mechanical ventilation and ECMO, and finally, this patient was successfully weaned from ECMO and the ventilator. No fibrosis lesions were found in the chest CT, and the patient recovered very well after leaving from the hospital for one month.
| S-EPMC7441876 | biostudies-literature
Project description: Not available
| S-EPMC7154570 | biostudies-literature
Project description:SARS-CoV-2 is a novel coronavirus that causes acute respiratory distress syndrome (ARDS), death and long-term sequelae. Innate immune cells are critical for host defense but are also the primary drivers of ARDS. The relationships between innate cellular responses in ARDS resulting from COVID-19 compared to other causes of ARDS, such as bacterial sepsis is unclear. Moreover, the beneficial effects of dexamethasone therapy during severe COVID-19 remain speculative, but understanding the mechanistic effects could improve evidence-based therapeutic interventions. To interrogate these relationships, we developed an scRNAseq atlas that is freely accessible (biernaskielab.ca/COVID_neutrophil). We discovered that compared to bacterial ARDS, COVID-19 was associated with distinct neutrophil polarization characterized by either interferon (IFN) or prostaglandin (PG) active states. Neutrophils from bacterial ARDS had higher expression of antibacterial molecules such as PLAC8 and CD83. Dexamethasone therapy in COVID patients rapidly altered the IFNactive state, downregulated interferon responsive genes, and activated IL1R2+ve neutrophils. Dexamethasone also induced the emergence of immature neutrophils expressing immunosuppressive molecules ARG1 and ANXA1, which were not present in healthy controls. Moreover, dexamethasone remodeled global cellular interactions by changing neutrophils from information receivers into information providers. Importantly, male patients had higher proportions of IFNactive neutrophils and a greater degree of steroid-induced immature neutrophil expansion. Indeed, the highest proportion of IFNactive neutrophils was associated with mortality. These results define neutrophil states unique to COVID-19 when contextualized to other life-threatening infections, thereby enhancing the relevance of our findings at the bedside. Furthermore, the molecular benefits of dexamethasone therapy are also defined. The identified molecular pathways can now be targeted to develop improved therapeutics.
2021-10-05 | PXD028429 | Pride
Project description:BACKGROUNDElevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes.METHODSWe used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTSFifteen hospitalized COVID-19 patients, 9 of whom were critically ill, were compared with critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONLevels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDINGFunding was received from NHLBI K23 HL125663 (AJR); The Bill and Melinda Gates Foundation OPP1113682 (AJR and CAB); Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687 NIH/NIAID U19AI057229-16; Stanford Maternal Child Health Research Institute; and Chan Zuckerberg Biohub (CAB).
| S-EPMC7526438 | biostudies-literature
Project description:Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14-68) years with COVID-19-induced ARDS. DSCs were administered 1-2 times at a dose of 1 × 106 /kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69-88) to 95% (range 78-99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0-253.4) to 11 (range 4.0-38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5-169) to 6 (range 2-31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3-12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19.
| S-EPMC8581334 | biostudies-literature