Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection.
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ABSTRACT:
SUBMITTER: Fernandez J
PROVIDER: S-EPMC7493773 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Plasma Exchange: An Effective Rescue Therapy in Critically Ill Patients With Coronavirus Disease 2019 Infection.
Fernandez Javier J Gratacos-Ginès Jordi J Olivas Pol P Costa Montserrat M Nieto Susana S Mateo Dolors D Sánchez María Belén MB Aguilar Ferran F Bassegoda Octavi O Ruiz Pablo P Caballol Berta B Pocurull Anna A Llach Joan J Mustieles María Jesús MJ Cid Joan J Reverter Enric E Toapanta Nestor David ND Hernández-Tejero María M Martínez José Antonio JA Claria Joan J Fernández Carlos C Mensa José J Arroyo Vicente V Castro Pedro P Lozano Miquel M
Critical care medicine 20201201 12
<h4>Objectives</h4>Infection by severe acute respiratory syndrome coronavirus-2 can induce uncontrolled systemic inflammation and multiple organ failure. The aim of this study was to evaluate if plasma exchange, through the removal of circulating mediators, can be used as rescue therapy in these patients.<h4>Design</h4>Single center case series.<h4>Setting</h4>Local study.<h4>Subjects</h4>Four critically ill adults with coronavirus disease 19 pneumonia that failed conventional interventions.<h4> ...[more]
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Project description:ObjectivesCoronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.DesignDaily blood inflammation profiling with immunoassays.SettingTertiary care ICU and academic laboratory.SubjectsAll patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative), or until ICU day 7 if the patient was positive (coronavirus disease 2019 positive).InterventionsNone.Measurements and main resultsAge- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. We measured 57 inflammatory analytes and then analyzed with both conventional statistics and machine learning. Twenty inflammatory analytes were different between coronavirus disease 2019 positive patients and healthy controls (p < 0.01). Compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had 17 elevated inflammatory analytes on one or more of their ICU days 1-3 (p < 0.01), with feature classification identifying the top six analytes between cohorts as tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2. While tumor necrosis factor, granzyme B, heat shock protein 70, and interleukin-18 were elevated for all seven ICU days, interferon-gamma-inducible protein 10 transiently elevated on ICU days 2 and 3 and elastase 2 increased over ICU days 2-7. Inflammation profiling predicted coronavirus disease 2019 status with 98% accuracy, whereas elevated heat shock protein 70 was strongly associated with mortality.ConclusionsWhile many inflammatory analytes were elevated in coronavirus disease 2019 positive ICU patients, relative to healthy controls, the top six analytes distinguishing coronavirus disease 2019 positive ICU patients from coronavirus disease 2019 negative ICU patients were tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.
| S-EPMC7314329 | biostudies-literature
Project description:BackgroundAcute respiratory distress syndrome is an important clinical presentation of respiratory complications caused by severe acute respiratory syndrome coronavirus 2, a novel coronavirus responsible for the ongoing pandemic. The disease is poorly understood, and immunopathogenesis is constantly evolving. Cytokine release syndrome remains central to pathology of coronavirus disease 2019. Antivirals, anticytokine treatment, and other pharmacological approaches have failed to treat it. CytoSorb, an extracorporeal cytokine adsorber that reduces the cytokine storm and other inflammatory mediators in the blood, seems promising in treating severely ill patients with coronavirus disease 2019.Case presentationThis article presents three cases of Asian ethnicity of severely ill adult patients with coronavirus disease 2019 admitted to intensive care unit who were treated with CytoSorb therapy. All patients used single CytoSorb device. During their clinical course, all patients were prescribed tocilizumab (an interleukin-6 receptor blocker), antivirals, hydroxychloroquine, azithromycin, and other antibiotics and general antipyretic drugs. No vasopressor treatment was required. The patients' average duration of stay in intensive care unit was 30 days; the average duration of stay in hospital was 31 days. All three patients showed significant improvement in biochemical parameters and clinical outcomes post CytoSorb therapy. C-reactive protein levels decreased by 91.5%, 97.4%, and 55.75 %, and mean arterial pressure improved by 18%, 23%, and 17 % in patient 1, 2, and 3, respectively, on day 7 post-therapy.ConclusionsAll three patients improved clinically and survived.
| S-EPMC8448661 | biostudies-literature
Project description:Objectives:Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic mediators and to identify potential outcome markers. Design:Blood was collected at predetermined ICU days for proximity extension assays to determine the plasma concentrations of 1,161 proteins. Setting:Tertiary care ICU and academic laboratory. Subjects:All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until ICU day 10 if the patient positive (coronavirus disease 2019 positive). Interventions:None. Measurements and Main Results:Age- and sex-matched healthy control subjects and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients suffered bilateral pneumonia more frequently than coronavirus disease 2019 negative patients. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Feature selection identified the top performing proteins for identifying coronavirus disease 2019 positive ICU patients from both healthy control subjects and coronavirus disease 2019 negative ICU patients (classification accuracies 100%). The coronavirus disease 2019 proteome was dominated by interleukins and chemokines, as well as several membrane receptors linked to lymphocyte-associated microparticles and/or cell debris. Mortality was predicted for coronavirus disease 2019 positive patients based on plasma proteome profiling on both ICU day 1 (accuracy 92%) and ICU day 3 (accuracy 83%). Promising prognostic proteins were then narrowed down to six, each of which provided excellent classification performance for mortality when measured on ICU day 1 CMRF-35-like molecule, interleukin receptor-12 subunit B1, cluster of differentiation 83 [CD83], family with sequence similarity 3, insulin-like growth factor 1 receptor and opticin; area-under-the-curve =1.0; p = 0.007). Conclusions:Targeted proteomics with feature classification easily distinguished both healthy control subjects and coronavirus disease 2019 tested negative ICU patients from coronavirus disease 2019 tested positive ICU patients. Multiple proteins were identified that accurately predicted coronavirus disease 2019 tested positive patient mortality.
| S-EPMC7449255 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) has resulted in high hospitalization rates worldwide. Acute kidney injury (AKI) in patients hospitalized for COVID-19 is frequent and associated with disease severity and poor outcome. The aim of this study was to investigate the incidence of kidney replacement therapy (KRT) in critically ill patients with COVID-19 and its implication on outcome.MethodsWe retrospectively analyzed all COVID-19 patients admitted to the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf (Germany) between 1 March 2020 and 31 July 2021. Demographics, clinical parameters, type of organ support, length of intensive care unit (ICU) stay, mortality and severity scores were assessed.ResultsThree-hundred critically ill patients with COVID-19 were included. The median age of the study population was 61 (IQR 51-71) years and 66% (n = 198) were male. 73% (n = 219) of patients required invasive mechanical ventilation. Overall, 68% (n = 204) of patients suffered from acute respiratory distress syndrome and 30% (n = 91) required extracorporeal membrane oxygenation (ECMO). We found that 46% (n = 139) of patients required KRT. Septic shock (OR 11.818, 95% CI: 5.941-23.506, p < 0.001), higher simplified acute physiology scores (SAPS II) (OR 1.048, 95% CI: 1.014-1.084, p = 0.006) and vasopressor therapy (OR 5.475, 95% CI: 1.127-26.589, p = 0.035) were independently associated with the initiation of KRT. 61% (n = 85) of patients with and 18% (n = 29) without KRT died in the ICU (p < 0.001). Cox regression found that KRT was independently associated with mortality (HR 2.075, 95% CI: 1.342-3.208, p = 0.001) after adjusting for confounders.ConclusionCritically ill patients with COVID-19 are at high risk of acute kidney injury with about half of patients requiring KRT. The initiation of KRT was associated with high mortality.
| S-EPMC9630840 | biostudies-literature
Project description:BackgroundSevere acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation, and inflammatory reaction, leading to acute respiratory failure and multi-organ dysfunction. Ongoing clinical trials are evaluating targeted therapies to hinder this exaggerated inflammatory response. Critically ill coronavirus disease 2019 (COVID-19) patients have shown heterogeneous severity trajectories, suggesting that response to therapies is likely to vary across patients.Research questionAre critically ill COVID-19 patients biologically and immunologically dissociable based on profiling of currently evaluated therapeutic targets?Study design and methodsWe did a single-center, prospective study in an ICU department in France. Ninety-six critically ill adult patients admitted with a documented SARS-CoV-2 infection were enrolled. We conducted principal components analysis and hierarchical clustering on a vast array of immunologic variables measured on the day of ICU admission.ResultsWe found that patients were distributed in three clusters bearing distinct immunologic features and associated with different ICU outcomes. Cluster 1 had a "humoral immunodeficiency" phenotype with predominant B-lymphocyte defect, relative hypogammaglobulinemia, and moderate inflammation. Cluster 2 had a "hyperinflammatory" phenotype, with high cytokine levels (IL-6, IL-1β, IL-8, tumor necrosis factor-alpha [TNF⍺]) associated with CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a "complement-dependent" phenotype with terminal complement activation markers (elevated C3 and sC5b-9).InterpretationPatients with severe COVID-19 exhibiting cytokine release marks, complement activation, or B-lymphocyte defects are distinct from each other. Such immunologic variability argues in favor of targeting different mediators in different groups of patients and could serve as a basis for patient identification and clinical trial eligibility.
| S-EPMC7831685 | biostudies-literature
Project description:BackgroundRecently, convalescent plasma (CP) transfusion was employed for severe or critically ill patients with coronavirus disease-2019. However, the benefits of CP for patients with different conditions are still in debate. To contribute clinical evidence of CP on critically ill patients, we analyze the characteristics and outcomes of patients with or without CP transfusion.MethodsIn this cohort study, 14 patients received CP transfusion based on the standard treatments, whereas the other 10 patients received standard treatments as control. Clinical characteristics and outcomes were analyzed. The cumulative survival rate was calculated by Kaplan-Meier survival analysis.ResultsData analysis was performed on 24 patients (male/female: 15/9) with a median age of 64.0 (44.5-74.5) years. Transient fever was reported in one patient. The cumulative mortality was 21% (3/14) in patients receiving CP transfusion during a 28-day observation, whereas one dead case (1/10) was reported in the control group. No significant difference was detected between groups in 28-day mortality (P = 0.615) and radiological alleviation of lung lesions (P = 0.085).ConclusionIn our current study, CP transfusion was clinically safe based on the safety profile; however, the clinical benefit was not significant in critically ill patients with more comorbidities at the late stage of disease during a 28-day observation.
| S-EPMC8390032 | biostudies-literature
Project description:ImportanceIn bacterial sepsis, CD14 and its N-terminal fragment (soluble CD14 subtype, "Presepsin") have been characterized as markers of innate immune responses and emerging evidence has linked both to coronavirus disease 2019 pathophysiology.ObjectivesOur aim was to determine the relationship between the soluble form of CD14 and soluble CD14 subtype plasma levels, coronavirus disease 2019 status, and coronavirus disease 2019-related outcomes.DesignA prospective cohort study.SettingICUs in three tertiary hospitals in Seattle, WA.ParticipantsTwo-hundred four critically ill patients under investigation for coronavirus disease 2019.Main outcomes and measuresWe measured plasma soluble CD14 and soluble CD14 subtype levels in samples collected upon admission. We tested for associations between biomarker levels and coronavirus disease 2019 status. We stratified by coronavirus disease 2019 status and tested for associations between biomarker levels and outcomes.ResultsAmong 204 patients, 102 patients had coronavirus disease 2019 and 102 patients did not. In both groups, the most common ICU admission diagnosis was respiratory failure or pneumonia and proportions receiving respiratory support at admission were similar. In regression analyses adjusting for age, sex, race/ethnicity, steroid therapy, comorbidities, and severity of illness, soluble CD14 subtype was 54% lower in coronavirus disease 2019 than noncoronavirus disease 2019 patients (fold difference, 0.46; 95% CI, 0.28-0.77; p = 0.003). In contrast to soluble CD14 subtype, soluble CD14 levels did not differ between coronavirus disease 2019 and noncoronavirus disease 2019 patients. In both coronavirus disease 2019 and noncoronavirus disease 2019, in analyses adjusting for age, sex, race/ethnicity, steroid therapy, and comorbidities, higher soluble CD14 subtype levels were associated with death (coronavirus disease 2019: adjusted relative risk, 1.21; 95% CI, 1.06-1.39; p = 0.006 and noncoronavirus disease 2019: adjusted relative risk, 1.19; 95% CI, 1.03-1.38; p = 0.017), shock, and fewer ventilator-free days. In coronavirus disease 2019 only, an increase in soluble CD14 subtype was associated with severe acute kidney injury (adjusted relative risk, 1.23; 95% CI, 1.05-1.44; p = 0.013).ConclusionsHigher plasma soluble CD14 subtype is associated with worse clinical outcomes in critically ill patients irrespective of coronavirus disease 2019 status though soluble CD14 subtype levels were lower in coronavirus disease 2019 patients than noncoronavirus disease 2019 patients. Soluble CD14 subtype levels may have prognostic utility in coronavirus disease 2019.
| S-EPMC8663850 | biostudies-literature
Project description:In critically ill patients with coronavirus disease 2019, there has been considerable debate about when to intubate patients with acute respiratory failure. Early expert recommendations supported early intubation. However, as we learned more about this disease, the risks versus benefits of early intubation are less clear. We report our findings from an observational study aimed to compare the difference in outcomes of critically ill patients with coronavirus disease 2019 who were intubated early versus later in the disease course. Early need for intubation was defined as intubation either at admission or within 2 days of having a documented Fio2 greater than or equal to 0.5. In the final sample of 111 patients, 76 (68%) required early intubation. The mean age among those who received early intubation was significantly higher (69.79 ± 12.15 vs 65.03 ± 8.37 years; p = 0.038). Also, the patients who required early intubation had significantly higher Sequential Organ Failure Assessment scores at admission (6.51 vs 3.48; p ≤ 0.0001). The outcomes were equivocal among both groups. In conclusion, we suggest that the timing of intubation has no impact on clinical outcomes among patients with coronavirus disease 2019 pneumonia.
| S-EPMC7587415 | biostudies-literature
Project description:OBJECTIVES:To determine mortality rates among adults with critical illness from coronavirus disease 2019. DESIGN:Observational cohort study of patients admitted from March 6, 2020, to April 17, 2020. SETTING:Six coronavirus disease 2019 designated ICUs at three hospitals within an academic health center network in Atlanta, Georgia, United States. PATIENTS:Adults greater than or equal to 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease who were admitted to an ICU during the study period. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Among 217 critically ill patients, mortality for those who required mechanical ventilation was 35.7% (59/165), with 4.8% of patients (8/165) still on the ventilator at the time of this report. Overall mortality to date in this critically ill cohort is 30.9% (67/217) and 60.4% (131/217) patients have survived to hospital discharge. Mortality was significantly associated with older age, lower body mass index, chronic renal disease, higher Sequential Organ Failure Assessment score, lower PaO2/FIO2 ratio, higher D-dimer, higher C-reactive protein, and receipt of mechanical ventilation, vasopressors, renal replacement therapy, or vasodilator therapy. CONCLUSIONS:Despite multiple reports of mortality rates exceeding 50% among critically ill adults with coronavirus disease 2019, particularly among those requiring mechanical ventilation, our early experience indicates that many patients survive their critical illness.
| S-EPMC7255393 | biostudies-literature
Project description:ObjectivesHypercoagulability may be a key mechanism for acute organ injury and death in patients with severe coronavirus disease 2019, but the relationship between elevated plasma levels of d-dimer, a biomarker of coagulation activation, and mortality has not been rigorously studied. We examined the independent association between d-dimer and death in critically ill patients with coronavirus disease 2019.DesignMulticenter cohort study.SettingICUs at 68 hospitals across the United States.PatientsCritically ill adults with coronavirus disease 2019 admitted to ICUs between March 4, 2020, and May 25, 2020, with a measured d-dimer concentration on ICU day 1 or 2.InterventionsNone.Measurements and main resultsThe primary exposure was the highest normalized d-dimer level (assessed in four categories: < 2×, 2-3.9×, 4-7.9×, and ≥ 8× the upper limit of normal) on ICU day 1 or 2. The primary endpoint was 28-day mortality. Multivariable logistic regression was used to adjust for confounders. Among 3,418 patients (63.1% male; median age 62 yr [interquartile range, 52-71 yr]), 3,352 (93.6%) had a d-dimer concentration above the upper limit of normal. A total of 1,180 patients (34.5%) died within 28 days. Patients in the highest compared with lowest d-dimer category had a 3.11-fold higher odds of death (95% CI, 2.56-3.77) in univariate analyses, decreasing to a 1.81-fold increased odds of death (95% CI, 1.43-2.28) after multivariable adjustment for demographics, comorbidities, and illness severity. Further adjustment for therapeutic anticoagulation did not meaningfully attenuate this relationship (odds ratio, 1.73; 95% CI, 1.36-2.19).ConclusionsIn a large multicenter cohort study of critically ill patients with coronavirus disease 2019, higher d-dimer levels were independently associated with a greater risk of death.
| S-EPMC8275993 | biostudies-literature