scholarly journals Glutamine and glutathione at ICU admission in relation to outcome

2012 ◽  
Vol 122 (12) ◽  
pp. 591-597 ◽  
Author(s):  
Paul Castillo Rodas ◽  
Olav Rooyackers ◽  
Christina Hebert ◽  
Åke Norberg ◽  
Jan Wernerman
Keyword(s):  
Risk Factor ◽  
Organ Failure ◽  
Independent Predictor ◽  
Apache Ii ◽  
University Hospital ◽  
Glutathione Depletion ◽  
Glutamine Supplementation ◽  
Limiting Factor ◽  
Icu Patients ◽  
Icu Admission

Glutamine depletion is demonstrated to be an independent predictor of hospital mortality in ICU (intensive care unit) patients. Today glutamine supplementation is recommended to ICU patients on parenteral nutrition. In addition to glutamine, glutathione may be a limiting factor in ICU patients with MOF (multiple organ failure). To study the prevalence of glutamine and glutathione depletion an observational study was performed. The results were analysed in relation to mortality and the conventional predictors of mortality outcome, APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment). Consecutive patients admitted to the ICU at Karolinska University Hospital Huddinge were studied. Patient admission scoring of APACHE II and SOFA were registered as well as mortality up to 6 months. Plasma glutamine concentration and whole blood glutathione status at admittance were analysed. The admission plasma glutamine concentrations were totally independent of the conventional risk scoring at admittance, and a subnormal concentration was an independent predictor of mortality. In addition, glutathione redox status was also an independent mortality predictor, but here a normal ratio was the risk factor. In both cases the mortality risk was mainly confined to the post-ICU period. A low plasma concentration of glutamine at ICU admission is an independent risk factor for post-ICU mortality. The possible benefit of extending glutamine supplementation post-ICU should be evaluated prospectively.

scholarly journals The impact of viremia on organ failure, biomarkers and mortality in a Swedish cohort of critically ill COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Josef D. Järhult ◽  
Michael Hultström ◽  
Anders Bergqvist ◽  
Robert Frithiof ◽  
Miklos Lipcsey
Keyword(s):  
Organ Failure ◽  
Critically Ill ◽  
Independent Predictor ◽  
Corticosteroid Treatment ◽  
Blood Stream ◽  
Common Finding ◽  
Icu Patients ◽  
Extra Pulmonary ◽  
The Impact ◽  
Swedish Cohort

AbstractThe spread of virus via the blood stream has been suggested to contribute to extra-pulmonary organ failure in Coronavirus disease 2019 (COVID-19). We assessed SARS-CoV-2 RNAemia (RNAemia) and the association between RNAemia and inflammation, organ failure and mortality in critically ill COVID-19 patients. We included all patients with PCR verified COVID-19 and consent admitted to ICU. SARS-CoV-2 RNA copies above 1000/ml measured by PCR in plasma was defined as RNAemia and used as surrogate for viremia. In this cohort of 92 patients 59 (64%) were invasively ventilated. RNAemia was found in 31 patients (34%). Hypertension and corticosteroid treatment was more common in patients with RNAemia. Extra-pulmonary organ failure biomarkers and the extent of organ failure were similar in patients with and without RNAemia, but the former group had more renal replacement therapy and higher mortality (26 vs 16%; 35 vs 16%, respectively, p = 0.04). RNAemia was not an independent predictor of death at 30 days after adjustment for age. SARS-CoV2 RNA copies in plasma is a common finding in ICU patients with COVID-19. Although viremia was not associated with extra pulmonary organ failure it was more common in patients who did not survive to 30 days after ICU admission.Trial registration: ClinicalTrials NCT04316884.

scholarly journals Association of Serum Calprotectin Concentrations with Mortality in Critically Ill and Septic Patients

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 990
Author(s):  
Theresa H. Wirtz ◽  
Lukas Buendgens ◽  
Ralf Weiskirchen ◽  
Sven H. Loosen ◽  
Nina Haehnsen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
University Hospital ◽  
Therapeutic Interventions ◽  
Neutrophil Granulocytes ◽  
Icu Patients ◽  
Long Term Outcome ◽  
Icu Admission

Background: Calprotectin is present in the cytosol of neutrophil granulocytes and released upon activation. Fecal calprotectin is applied in the clinical management of inflammatory bowel disease whereas serum calprotectin has been discussed as a biomarker in inflammatory disorders. However, its long-term prognostic relevance in critical illness remains unclear. Our aim was to investigate serum calprotectin concentrations as a prognostic biomarker in critically ill and septic patients. Methods: Serum calprotectin concentrations were analyzed in 165 critically ill patients (108 with sepsis, 57 without sepsis) included in our observational study. Patients were enrolled upon admission to the medical intensive care unit (ICU) of the RWTH Aachen University Hospital. Calprotectin concentrations were compared to 24 healthy controls and correlated with clinical parameters, therapeutic interventions, and survival. Results: Serum calprotectin concentrations were significantly increased in ICU patients as well as in septic patients compared to respective controls (p < 0.001 for ICU patients and p = 0.001 for septic patients). Lower calprotectin concentrations were measured in patients with comorbidities i.e., coronary artery disease. Calprotectin concentrations strongly correlated with the C-reactive protein (p < 0.001) and were closely associated to parameters of mechanical ventilation (i.a. inspiratory oxygen fraction, FiO2; p < 0.001). The overall survival was significantly impaired in septic patients with high baseline calprotectin concentrations (p = 0.036). However, patients with increasing calprotectin serum concentrations within the first week of ICU admission showed an improved overall survival (p = 0.009). Conclusions: In summary, serum calprotectin concentrations are significantly increased in critically ill patients with sepsis. High calprotectin concentrations at ICU admission predict long-term mortality risk, whereas increasing calprotectin concentrations are associated with a favorable long-term outcome.

scholarly journals Alcohol withdrawal syndrome in ICU patients: Clinical features, management, and outcome predictors

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261443
Author(s):  
Aliénor Vigouroux ◽  
Charlotte Garret ◽  
Jean-Baptiste Lascarrou ◽  
Maëlle Martin ◽  
Arnaud-Félix Miailhe ◽  
...  
Keyword(s):  
Hospital Stay ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Delirium Tremens ◽  
Multivariable Analysis ◽  
Alcohol Withdrawal Syndrome ◽  
University Hospital ◽  
Icu Patients ◽  
Icu Admission ◽  
Organ Dysfunctions

Background Alcohol withdrawal syndrome (AWS) is a common condition in hospitalized patients, yet its epidemiology in the ICU remains poorly characterized. Methods Retrospective cohort of patients admitted to the Nantes University Hospital ICU between January 1, 2017, and December 31, 2019, and coded for AWS using ICD-10 criteria. The objective of the study was to identify factors associated with complicated hospital stay defined as ICU length of stay ≥7 days or hospital mortality. Results Among 5,641 patients admitted to the ICU during the study period, 246 (4.4%) were coded as having AWS. Among them, 42 had exclusion criteria and 204 were included in the study. The three main reasons for ICU admission were sepsis (29.9%), altered consciousness (29.4%), and seizures (24%). At ICU admission, median Cushman’s score was 6 [4–9] and median SOFA score was 3 [2–6]. Delirium tremens occurred in half the patients, seizures in one fifth and pneumonia in one third. Overall, 48% of patients developed complicated hospital stay, of whom 92.8% stayed in the ICU for ≥7 days, 36.7% received MV for ≥7 days, and 16.3% died during hospital stay. By multivariable analysis, two factors were associated with complicated hospital stay: a higher number of organ dysfunctions at ICU admission was associated with a higher risk of complicated hospital stay (OR, 1.18; 95CI, 1.05–1.32, P = 0.005), whereas ICU admission for seizures was associated with a lower risk of complicated hospital stay (OR, 0.14; 95%CI, 0.026–0.80; P = 0.026). Conclusions AWS in ICU patients chiefly affects young adults and is often associated with additional factors such as sepsis, trauma, or surgery. Half the patients experienced an extended ICU stay or death during the hospital stay. The likelihood of developing complicated hospital stay relied on the reason for ICU admission and the number of organ dysfunctions at ICU admission.

Predictors of Mortality in Patients Undergoing Autologous Stem Cell Transplant (ASCT) Admitted to the Intensive Care Unit: An Institutional Review of 1013 Transplant Patients over Five Years.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2876-2876
Author(s):  
Martina A. Trinkaus ◽  
Stephen E. Lapinsky ◽  
David C. Hallett ◽  
Norman Franke ◽  
Andrew Winter ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Multiple Myeloma ◽  
Mechanical Ventilation ◽  
Intensive Care ◽  
Febrile Neutropenia ◽  
Organ Failure ◽  
Admission Rate ◽  
Apache Ii ◽  
Gram Negative ◽  
Icu Admission

Abstract Study Objective: To describe the outcomes of ASCT recipients transferred to the Intensive Care Unit (ICU), and identify predictors for mortality. Methods: Retrospective review of all ASCT recipients from Jan 2001-July 2006 who required ICU transfer up to 100 days post ASCT. Measurements and main Results: Thirty-four of 1013 patients (3.3%) who underwent ASCT, were admitted to the ICU. The mean age at admission was 54.9 +/− 11.1 (range 28–71), 53% being female. Indications for ASCT included multiple myeloma (50%), amyloidosis (32%), or other malignancies (18%). Table 1 highlights the admission rate to the ICU by diagnosis. The primary admitting diagnosis in the ICU included sepsis (32%), cardiac related events (26%), or respiratory compromise (29%). Median days post ASCT was 10.0 days with a median in ICU stay of 4.0 days (range 1–37 days). Twenty patients (including all non-survivors) required mechanical ventilation for > 24 hours with a median duration of 3.0 days. Thirteen patients died (38%) in the ICU, with 11 dying of multi-system organ failure and 2 from cardiac arrest. Retrospectively collected parameters restricted to the first 24 hours of admission revealed that Sequential Organ Failure Assessment (SOFA) score (OR 1.30; CI95 1.09–1.64, P=0.003) and Acute Physiology and Chronic Health Evaluation (APACHE II) score (OR 1.43; CI95 1.14–2.16; P=0.0002) were statistically associated with mortality in univariate analysis. The variables predictive of mortality at 24 hours after admission are displayed in Table 2. Conclusion: ICU admission is uncommon, occuring in 3% of patients undergoing ASCT, of which 38% die (1% of total ASCTs). Admission is influenced by underlying diagnosis, with amyloid patients portending the highest risk. Mortality in ASCT patients admitted to the ICU can be predicted in the first 24 hours by specific assessment scores (SOFA and APACHE II); specific supportive care requirements: inotropic dependence, hemodialysis, and need for ventilation; and clinical findings of gram negative sepsis or > 2 organ failure. Patients with febrile neutropenia had a low risk of mortality (possibly due to aggressive antibiotic use, growth factors, and rapid engraftment post ASCT). These results may assist clinical decision making regarding the continuation of intensive care delivered 24 hours after admission. Percentage Admission Rate by Diagnosis (n = 1013) Diagnosis ASCT (#) ICU Admission (#)/ (%) Non-survivors (#) Multiple Myeloma 615 17 / (2.8%) 6 Non-Hodgkin’s Lymphoma 199 2/ (1.0%) 1 Hodgkin’s Lymphoma 112 1 / (0.9%) 0 Amyloidosis 39 11/ (28.2%) 6 Acute Myeloid Leukemia 17 1/ (5.9%) 0 Other (Germ Cell Tumour, Waldenstrom’s Macroglobuliemia, POEMS) 31 2/ (6.4%) 0 Variables Predictive of Mortality at 24 hours after Admission Variable Predictors Number of Patients Survivors (n = 21) Non-survivors (n = 13) P-value Febrile Neutropenia 15 13 (62%) 2 (15%) 0.013 Failure of > 2 organs 20 9 (43%) 11 (85%) 0.030 Mechanical Ventilation 20 9 (43%) 11 (85%) 0.030 Inotropic Support > 4 hours 10 3 (14%) 7 (54%) 0.022 Hemodialysis 12 4 (19%) 8 (62%) 0.025 Gram Negative Infection 6 1 (5%) 5 (42%) 0.016

Factors Predicting the Outcome of the Blood and Marrow Transplant Patients Admitted to Intensive Care Unit.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3340-3340
Author(s):  
Nalini K Pati ◽  
Biju George ◽  
Ian Kerridge ◽  
Nicole Gilroy ◽  
Vineet Nayyar ◽  
...  
Keyword(s):  
Intensive Care ◽  
Organ Failure ◽  
Apache Ii ◽  
Haematopoietic Stem Cell ◽  
Apache Ii Score ◽  
Allogeneic Hsct ◽  
Icu Admission ◽  
Poor Outcome ◽  
Organ Failures ◽  
Steroid Refractory

Abstract Abstract 3340 Poster Board III-228 Aim: To identify factors predicting outcome of patients admitted to intensive care (ICU) following allogeneic haematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective audit of all allo-HSCT patients requiring ICU admission. Results: Between 2000 and 2009, 392 patients underwent allo-HSCT. Of these, 106 (27%) had 129 ICU admissions. The median age was 47 (range 16-65) with myeloablative transplant in 89 and reduced intensity in 40 patients. Respiratory failure was the main reason for admission (54.6%) followed by sepsis (41.5%). During the period of ICU admission, 29.2% demonstrated improvement in organ failures, 39.2% remained stable and 28.4% deteriorated. Sixty-seven patients (51.9%) were discharged from ICU but only 48 (37%) were subsequently discharged from the hospital (ICU). Univariate analysis identified ICU admission within 30 days post HSCT, number of organ failures at admission, progression of organ failure during ICU admission, APACHE II score at admission, steroid refractory GVHD, and requirement for inotropic support or dialysis as significant predictors for survival in ICU. Patients requiring intubation and mechanical ventilation had a poorer outcome than the group who did not (84.4% Vs 20.0%, p=0.001). Those who required only non-invasive ventilation generally had a good outcome with 84.4% surviving til ICU discharge. While bacterial infection prior to ICU admission did not alter the outcome (p=0.221), the onset of a new infection in ICU was associated with a poor outcome (p=0.0001). Logistic regression analysis identified steroid refractory GvHD (P=0.027; 95% CI of 1.17-14.8), APACHE II score > 30 (p=0.003; 95% CI 1.5-10.5), admission <30 days post HSCT (p = 0.015; 95% CI 0.12-0.8), requirement of invasive ventilatory support (p = 0.005, 95% CI 2.58 – 223.83) and dialysis (p = 0.011; 95%CI 1.401 – 13.20) as significant factors for a poor outcome. Conclusion: More than 50% of patients admitted to ICU following allogeneic HSCT survive. A high APACHE II score, steroid refractory GVHD, admission into ICU within 30 days of HSCT, multiorgan failure, progression of organ failure during ICU stay, and the need for ventilation or dialysis, carries a dismal prognosis. Identification of risk factors associated with a poor outcome will assist in clinical management and may ultimately improve the outcome of patients requiring ICU admission following allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Lactate Kinetics Reflect Organ Dysfunction and Are Associated with Adverse Outcomes in Intensive Care Unit Patients with COVID-19 Pneumonia: Preliminary Results from a GREEK Single-Centre Study

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 386
Author(s):  
Alice G. Vassiliou ◽  
Edison Jahaj ◽  
Ioannis Ilias ◽  
Vassiliki Markaki ◽  
Sotirios Malachias ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Blood Lactate ◽  
Organ Dysfunction ◽  
Apache Ii ◽  
Icu Mortality ◽  
Icu Patients ◽  
Time Pattern ◽  
Cox Regression Analysis ◽  
Icu Admission

Coronavirus disease-19 (COVID-19) continues to be a health threat worldwide. Increased blood lactate is common in intensive care unit (ICU) patients; however, its association with outcomes in ICU COVID-19 patients remains currently unexplored. In this retrospective, observational study we assessed whether lactate is associated with outcomes in COVID-19 patients. Blood lactate was measured on ICU admission and thereafter daily up to day 14 in 45 patients with confirmed COVID-19 pneumonia. Acute physiology and chronic health evaluation (APACHE II) was calculated on ICU admission, and sequential organ failure assessment (SOFA) score was assessed on admission and every second day. The cohort was divided into survivors and non-survivors based on 28-day ICU mortality (24.4%). Cox regression analysis revealed that maximum lactate on admission was independently related to 28-day ICU mortality with time in the presence of APACHE II (RR = 2.45, p = 0.008). Lactate’s area under the curve for detecting 28-day ICU mortality was 0.77 (p = 0.008). Mixed model analysis showed that mean daily lactate levels were higher in non-survivors (p < 0.0001); the model applied on SOFA scores showed a similar time pattern. Thus, initial blood lactate was an independent outcome predictor in COVID-19 ICU patients. The time course of lactate mirrors organ dysfunction and is associated with poor clinical outcomes.

scholarly journals Body Mass Index is not an Independent Predictor for Missed Injury on Chest X-ray compared with Chest Computed Tomography

2013 ◽  
Vol 2 (1) ◽  
pp. 45-48
Author(s):  
Rahul Anand ◽  
Michel Aboutanos ◽  
Rao Ivatury ◽  
Poornima Vanguri
Keyword(s):  
Computed Tomography ◽  
Body Mass Index ◽  
Risk Factor ◽  
Hospital Stay ◽  
Independent Predictor ◽  
Chest Computed Tomography ◽  
X Ray ◽  
Icu Admission ◽  
Missed Injury ◽  
Chest X Ray

ABSTRACT Objective Obesity is a risk factor for morbidity and mortality in the polytraumatized patient. The aim of this study is to determine if obesity is an independent risk factor for missed injury in chest X-ray after trauma. Materials and methods Institutional Review Board approval was obtained. We performed a retrospective review of patients who presented to a level one trauma center as the higher acuity alerts from September 2010 to July 2011. We compared the chest X-ray with the chest computed tomography (CT) findings. Variables, such as age, BMI, mechanism, admission to the ICU and mortality during the same hospital stay, were evaluated. Results A total of 224 patients met these criteria. The majority of patients were of male gender (79%). Average age was 40 years. Average ISS was 19.7. Mean BMI was 26.7 with 103 patients with BMI < 25 and with 123 patients with BMI >25. Mechanisms included blunt (n = 167), penetrating (n = 50) and burns (n = 7). A total of 123 patients (54.4%) had undiagnosed thoracic injuries by chest X-ray that were found on chest CT scan. Eighty-five percent of patients with missed injuries on chest X-ray required ICU admission as a result of the thoracic trauma. Missed injuries were as follows; rib fractures with or without flail chest (n = 62), pneumothorax (n = 40), hemothorax (n = 42), sternal fracture (n = 15), pulmonary lacerations/contusion (n = 60), great vessel injuries (n = 6), and blunt ventricular rupture (n = 1). Strikingly, there was no significant difference in missed injury, ICU admission or mortality when obese patients were compared to nonobese patients. Conclusion Chest X-ray undermines the degree of injury in blunt trauma patients. BMI is not an independent predictor of missed injury, ICU admission or mortality during the same hospital stay. How to cite this article Vanguri P, Anand R, Aboutanos M, Ivatury R, Ferrada P. Body Mass Index is not an Independent Predictor for Missed Injury on Chest X-ray compared with Chest Computed Tomography. Panam J Trauma Critical Care Emerg Surg 2013;2(1):45-48.

scholarly journals A Novel Assay of Neutrophil Extracellular Traps (NETs) Formation Independently Predicts DIC and Identifies the Rationale for Anti-IL-8 Therapies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 440-440
Author(s):  
Simon Timothy Abrams ◽  
Ben Morton ◽  
Yasir Alhamdi ◽  
Mohmad Alsabani ◽  
Zhenxing Cheng ◽  
...  
Keyword(s):  
Organ Failure ◽  
Conflicts Of Interest ◽  
Clinical Care ◽  
Neutrophil Extracellular Traps ◽  
Protective Mechanism ◽  
Positive Staining ◽  
Icu Patients ◽  
Intravascular Coagulation ◽  
Icu Admission ◽  
Extracellular Traps

Background Neutrophils are the first line of defence against bacterial infection and formation of neutrophil extracellular traps (NETs) is an important protective mechanism. However, NETs can also cause harm by promoting intravascular coagulation and multi-organ failure (MOF) in animal models. Although increasingly considered as important therapeutic targets, there is currently no robust and specific measure of NETs formation to inform clinical care and enable precision medicine in patients on the intensive care unit (ICU). The aim of this study is to establish a novel assay for measuring NETs and assess its clinical significance. Methods A prospective cohort of 341 consecutive adult ICU patients was recruited, following written informed consent. The NETs-forming capacity of ICU admission blood samples was semi-quantified by directly incubating patient plasma with isolated healthy neutrophils ex vivo. The association of NETs-forming capacity with sequential organ failure assessment (SOFA) scores, disseminated intravascular coagulation (DIC) and 28-day mortality were analysed and compared with available NETs assays. Cytokine analysis together with inhibitor studies was performed to determine the driving factors of NETs patients. To determine the pathological relevance of NETs, complementary in vivo studies were performed in mice models of sepsis (caecal ligation and puncture (CLP) or intraperitoneal injection of Escherichia coli), without or with anti-NETs therapy. Results We observed that NETs were directly induced by heterologous healthy neutrophils incubated with plasma taken from ICU patients, but not from healthy donors (unless incubated with 100 nM PMA). Using the novel assay, we could stratify ICU patients into 4 groups, those with absent (22.0%), mild (49.9%), moderate (14.4%) and strong (13.8%) NETs formation, respectively. Strong NETs formation was predominantly found in sepsis (P &lt;0.0001) and was associated with higher SOFA scores on admission and throughout the study duration (72 hours post-admission). Adjusted by APACHE II, multivariate regression showed that measuring the degree of NETs formation in ICU admission could independently predict DIC and mortality whereas other NETs assays, e.g. cell-free DNA, myeloperoxidase and myeloperoxidase-DNA complexes, could not. Interleukin (IL)-8 levels were found to be strongly associated with NETs formation and inhibiting IL-8 significantly attenuated NETosis. MAPK activation by IL-8 has been identified as a major pathway of NETs formation in patients. Using mice models of sepsis, we specifically observed NETs positive staining (cit-H3) in the lung tissue. This was associated with increases in lung injury scores, along with circulating markers of liver (BUN [CLP: P=0.005, E.coli: P&lt;0.001]), kidney (ALT [CLP: P=0.01, E.coli: P=0.002]) and cardiac injury (cTnI [(CLP: P&lt;0.001, E.coli: P&lt;0.001]). By targeting IL-8 we were able to significantly inhibit NETs formation, organ injury and also improved survival times in septic mice (P=0.004). Conclusions Our new NETs assay directly measures the NETs-forming capacity in patient plasma. This could guide clinical management and enable identification of NETs-inducing factors in individual patients for targeted treatment and personalised ICU medicine. We identify IL-8 as a major driving factor in sepsis, with anti-IL-8 therapy in septic mice significantly reducing NETs-induced organ damage and mortality. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Pavan K. Bhatraju ◽  
Eric D. Morrell ◽  
Leila Zelnick ◽  
Neha A. Sathe ◽  
Xin-Ya Chai ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Epithelial Cell ◽  
Acute Phase ◽  
Cell Injury ◽  
Acute Phase Proteins ◽  
Invasive Mechanical Ventilation ◽  
Icu Patients ◽  
Icu Admission ◽  
Amyloid A ◽  
Epithelial Cell Injury

Abstract Background Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. Methods We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. Results In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. Conclusions These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.

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