Dataset Information

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

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.

SUBMITTER: Bhatraju PK

PROVIDER: S-EPMC8054255 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:ICU patients undergoing invasive mechanical ventilation experience cognitive decline associated with their critical illness and its management. The early detection of different cognitive phenotypes might reveal the involvement of diverse pathophysiological mechanisms and help to clarify the role of the precipitating and predisposing factors. Our main objective is to identify cognitive phenotypes in critically ill survivors 1 month after ICU discharge using an unsupervised machine learning method, and to contrast them with the classical approach of cognitive impairment assessment. For descriptive purposes, precipitating and predisposing factors for cognitive impairment were explored. METHODS:A total of 156 mechanically ventilated critically ill patients from two medical/surgical ICUs were prospectively studied. Patients with previous cognitive impairment, neurological or psychiatric diagnosis were excluded. Clinical variables were registered during ICU stay, and 100 patients were cognitively assessed 1 month after ICU discharge. The unsupervised machine learning K-means clustering algorithm was applied to detect cognitive phenotypes. Exploratory analyses were used to study precipitating and predisposing factors for cognitive impairment. RESULTS:K-means testing identified three clusters (K) of patients with different cognitive phenotypes: K1 (n?=?13), severe cognitive impairment in speed of processing (92%) and executive function (85%); K2 (n?=?33), moderate-to-severe deficits in learning-memory (55%), memory retrieval (67%), speed of processing (36.4%) and executive function (33.3%); and K3 (n?=?46), normal cognitive profile in 89% of patients. Using the classical approach, moderate-to-severe cognitive decline was recorded in 47% of patients, while the K-means method accurately classified 85.9%. The descriptive analysis showed significant differences in days (p?=?0.016) and doses (p?=?0.039) with opioid treatment in K1 vs. K2 and K3. In K2, there were more women, patients were older and had more comorbidities (p?=?0.001) than in K1 or K3. Cognitive reserve was significantly (p?=?0.001) higher in K3 than in K1 or K2. CONCLUSION:One month after ICU discharge, three groups of patients with different cognitive phenotypes were identified through an unsupervised machine learning method. This novel approach improved the classical classification of cognitive impairment in ICU survivors. In the exploratory analysis, gender, age and the level of cognitive reserve emerged as relevant predisposing factors for cognitive impairment in ICU patients. TRIAL REGISTRATION:ClinicalTrials.gov Identifier:NCT02390024; March 17,2015.

Project description:BackgroundVaccines against COVID-19 show high efficacy, yet, infection is still being detected among immunized patients, although with blunted severity. The purpose of this study was to assess the severity of COVID-19 infection among immunized versus non-immunized COVID-19 patients admitted to ICU.MethodA prospective observational cohort study, including all COVID-19 patients admitted to intensive care unit between January 1st, 2021 and June 30th, 2021 were eligible for inclusion. A comparison of severity upon hospitalization of immunized versus non-immunized patients on a 7-level ordinal scale was conducted, using ordinal logistic regression.Results592 patients were enrolled, 524 (88.5%) non-immunized, 63 (10.6%) partially immunized, and 5 (0.9%) fully immunized, partially and fully immunized patients were grouped together. Majority of immunized patients (86.7%) were symptomatic before 21 days of immunization. Non-immunized group had fewer patients in the lower severity categories, while more patients in the higher severity categories compared to immunized group. At least one dose of immunization was associated with reduction of odds of moving up severity scale (OR = 0.2 [95% CI: 0.15-0.4]; p < 0.001) in a well fitted ordinal logistic regression model. At least one dose of immunization was associated with lower adjusted odds of 30 day all-cause mortality (OR = 0.45 [95% CI: 0.23-0.89]; p = 0.02). Non-immunized group had higher mortality rate (43.9% versus 29.4% [95% CI: 1.5 to 25.8]; p = 0.02).ConclusionMost COVID-19 patients admitted to ICU were non-immunized, most of the partially immunized patients got infected before immunity could develop, and fully immunized patients were likely non-responders. At least one dose of immunization significantly decreases severity of the disease across all ordinal severity categories, and is significantly associated with lower 30 day all-cause mortality. Accordingly, immunization status may have to be considered when deciding on disposition of COVID-19 patients at the point of triage.

Project description:IntroductionIntracranial pressure (ICP) monitoring is commonly used in neurocritical care patients with acute brain injury (ABI). Practice about indications and use of ICP monitoring in patients with ABI remains, however, highly variable in high-income countries, while data on ICP monitoring in low and middle-income countries are scarce or inconsistent. The aim of the SYNAPSE-ICU study is to describe current practices of ICP monitoring using a worldwide sample and to quantify practice variations in ICP monitoring and management in neurocritical care ABI patients.Methods and analysisThe SYNAPSE-ICU study is a large international, prospective, observational cohort study. From March 2018 to March 2019, all patients fulfilling the following inclusion criteria will be recruited: age >18 years; diagnosis of ABI due to primary haemorrhagic stroke (subarachnoid haemorrhage or intracranial haemorrhage) or traumatic brain injury; Glasgow Coma Score (GCS) with no eye opening (Eyes response=1) and Motor score ≤5 (not following commands) at ICU admission, or neuro-worsening within the first 48 hours with no eye opening and a Motor score decreased to ≤5. Data related to clinical examination (GCS, pupil size and reactivity, Richmond Agitation-Sedation Scale score, neuroimaging) and to ICP interventions (Therapy Intensity Levels) will be recorded on admission, and at day 1, 3 and 7. The Glasgow Outcome Scale Extended (GOSE) will be collected at discharge from ICU and from hospital and at 6-month follow-up. The impact of ICP monitoring and ICP-driven therapy on GOSE will be analysed at both patient and ICU level.Ethics and disseminationThe study has been approved by the Ethics Committee 'Brianza' at the Azienda Socio Sanitaria Territoriale (ASST)-Monza (approval date: 21 November 2017). Each National Coordinator will notify the relevant ethics committee, in compliance with the local legislation and rules. Data will be made available to the scientific community by means of abstracts submitted to the European Society of Intensive Care Medicine annual conference and by scientific reports and original articles submitted to peer-reviewed journals.Trial registration numberNCT03257904.

Project description:Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid). Plasma was collected at enrolment, 48 hours later and hospital discharge. We measured biomarkers of inflammation (IL-6, ferritin), endothelial activation (Ang-1, Ang-2, sTie-2, VCAM-1) and endothelial glycocalyx breakdown (hyaluronan, heparan sulfate, endocan, syndecan-1). We enrolled 135 patients with DS (median age 26, median SOFA score 7, 34 required ICU admission, 5 deaths), together with 37 patients with SS and 25 healthy controls. Within the DS group, IL-6 and ferritin were associated with admission SOFA score (IL-6: βeta0.70, p<0.001 & ferritin: βeta0.45, p<0.001), ICU admission (IL-6: OR 2.6, p<0.001 & ferritin: OR 1.55, p<0.001) and mortality (IL-6: OR 4.49, p = 0.005 & ferritin: OR 13.8, p = 0.02); both biomarkers discriminated survivors and non-survivors at 48 hours and all patients who died from DS had pre-mortem ferritin ≥100,000ng/ml. IL-6 most strongly correlated with severity of pulmonary vascular leakage (R = 0.41, p<0.001). Ang-2 correlated with pulmonary vascular leak (R = 0.33, p<0.001) and associated with SOFA score (β 0.81, p<0.001) and mortality (OR 8.06, p = 0.002). Ang-1 was associated with ICU admission (OR 1.6, p = 0.005) and mortality (OR 3.62, p = 0.006). All 4 glycocalyx biomarkers were positively associated with SOFA score, but only syndecan-1 was associated with ICU admission (OR 2.02, p<0.001) and mortality (OR 6.51, p<0.001). This study highlights the central role of hyperinflammation in determining outcomes from DS; the data suggest that anti-IL-1 and anti-IL-6 immune modulators and Tie2 agonists may be considered as candidates for therapeutic trials in severe dengue.

Project description:IntroductionCancer patients are at high risk of developing septic shock (SSh) and are increasingly admitted to ICU given their improved long-term prognosis. We, therefore, compared the prognosis of cancer and non-cancer patients with SSh.MethodsWe conducted a monocentric, retrospective cohort study (2013-2019) on patients admitted to ICU for SSh. We compared the clinical characteristics and management and studied short- and long-term mortality with ICU and in-hospital mortality and 1-year survival according to cancer status.ResultsWe analyzed 239 ICU stays in 210 patients, 59.5% of whom were men (n = 125), with a median age of 66.5 (IQR 56.3-77.0). Of the 121 cancer patients (57.6% of all patients), 70 had solid tumors (33.3%), and 51 had hematological malignancies (24.3%). When comparing ICU stays of patients with versus without cancer (n = 148 vs. n = 91 stays, respectively), mortality reached 30.4% (n = 45) vs. 30.0% (n = 27) in the ICU (p = 0.95), and 41.6% (n = 59) vs. 35.6% (n = 32) in hospital (p = 0.36), respectively. ICU length of stay (LOS) was 5.0 (2.0-11.3) vs. 6.0 (3.0-15.0) days (p = 0.27), whereas in-hospital LOS was 25.5 (13.8-42.0) vs. 19.5 (10.8-41.0) days (p = 0.33). Upon multivariate analysis, renal replacement therapy (OR = 2.29, CI95%: 1.06-4.93, p = 0.03), disseminated intravascular coagulation (OR = 5.89, CI95%: 2.49-13.92, p < 0.01), and mechanical ventilation (OR = 7.85, CI95%: 2.90-21.20, p < 0.01) were associated with ICU mortality, whereas malignancy, hematological, or solid tumors were not (OR = 1.41, CI95%: 0.65-3.04; p = 0.38). Similarly, overall cancer status was not associated with in-hospital mortality (OR = 1.99, CI95%: 0.98-4.03, p = 0.06); however, solid cancers were associated with increased in-hospital mortality (OR = 2.52, CI95%: 1.12-5.67, p = 0.03). Lastly, mortality was not significantly different at 365-day follow-up between patients with and without cancer.ConclusionsIn-hospital and ICU mortality, as well as LOS, were not different in SSh patients with and without cancer, suggesting that malignancies should no longer be considered a barrier to ICU admission.