Association of Altered Plasma Lipidome with Disease Severity in COVID-19 Patients

The severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). This is the third publication in a series, and it reports the results of comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, and sphingolipids, among which 531 lipid features were dramatically changed in the plasma of intensive care unit (ICU) patients compared to patients in the ward. Patients in the ICU showed 1.3-57-fold increases in ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, and plasmagen phosphoethanolamines, and 1.3-2-fold lower levels of a cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, and cholesterol esters compared to patients in the ward. Specifically, phosphatidylinositols (PIs) showed strong fatty acid saturation-dependent behavior, with saturated fatty acid (SFA)- and monosaturated fatty acid (MUFA)-derived PI decreasing and polystaturated (PUFA)-derived PI increasing. We also found ~4000 significant Spearman correlations between lipids and multiple clinical markers of immune response with |R| ≥ 0.35 and FDR corrected Q < 0.05. Except for lysophosphatidic acid, lysophospholipids were positively associated with the CD4 fraction of T cells, and the cytokines IL-8 and IL-18. In contrast, sphingosine-1-phosphates were negatively correlated with innate immune markers such as CRP and IL-6. Further indications of metabolic changes in moderate COVID-19 disease were demonstrated in recovering ward patients compared to those at the start of hospitalization, where 99 lipid species were altered (6 increased by 30-62%; 93 decreased by 1.3-2.8-fold). Overall, these findings support and expand on early reports that dysregulated lipid metabolism is involved in COVID-19

A novel haemocytometric covid-19 prognostic score developed and validated in an observational multicentre european hospital-based study

COVID-19 induces haemocytometric changes. Complete blood count changes, including new cell activation parameters, from 982 confirmed COVID-19 adult patients from 11 European hospitals were retrospectively analysed for distinctive patterns based on age, gender, clinical severity, symptom duration and hospital days. The observed haemocytometric patterns formed the basis to develop a multi-haemocytometric-parameter prognostic score to predict, during the first three days after presentation, which patients will recover without ventilation or deteriorate within a two-week timeframe, needing intensive care or with fatal outcome. The prognostic score, with ROC curve AUC at baseline of 0.753 (95% CI 0.723-0.781) increasing to 0.875 (95% CI 0.806-0.926) on day 3, was superior to any individual parameter at distinguishing between clinical severity. Findings were confirmed in a validation cohort. Aim is that the score and haemocytometry results are simultaneously provided by analyser software, enabling wide applicability of the score as haemocytometry is commonly requested in COVID-19 patients

The role of C-reactive protein and the SOFA score as parameter for clinical decision making in surgical patients during the intensive care unit course.

INTRODUCTION: C-reactive Protein (CRP) is used next to clinical scoring systems to recognize critically ill patients prone to develop complications on the Intensive Care Unit (ICU). The purpose of this study is to assess the predictive value of CRP as parameter for clinical deterioration and/or clinical decision making as ordering diagnostic procedures or performing (re)interventions. Also, we wanted to determine the value of CRP in early detection of surgical complications in the critically ill general surgical patient in the ICU and its interpretation in adjunct to a clinical scoring system, the Sequential Organ Failure Assessment Score. MATERIALS AND METHODS: In our prospective observational study, 174 general surgical patients admitted into the Intensive Care Unit were included. We evaluated the Sequential Organ Failure Assessment Score (SOFA) and daily measured the C-reactive protein (CRP) concentrations. All events (diagnostic or therapeutic interventions) and surgical complications were registered. Then the relationship between SOFA score, CRP concentrations, events and complications were studied. RESULTS: Each 10% increase in CRP resulted in a 3.5% increase in the odds of an event (odds ratio 1.035, 95% CI: 1.004-1.068; p = 0.028). However, an increase in CRP levels did not lead to a higher odds of complication (OR 0.983, 95% CI: 0.932-1.036; p = 0.52). When adjusting for the SOFA score the effect of CRP on the probability of a first event remained significant (OR 1.033, 95% CI: 1.001-1.065; p = 0.046), and again did not significantly affect the complication probability (OR 0.980, 95% CI: 0.929-1.035; p = 0.46). CONCLUSIONS: An increase in C-reactive protein is a poor parameter for early detection of complications in the critically ill surgical patient in the ICU by means of diagnostic procedures or therapeutic (re)-interventions

Oral tobramycin prophylaxis prior to colorectal surgery is not associated with systemic uptake

Preoperative oral prophylaxis with nonabsorbable antibiotics has been reported to reduce the risk of surgical site infections after colorectal surgery. This prospective study was conducted to evaluate the risk of toxic side effects by measuring postoperative serum tobramycin levels in patients who received a 3-day prophylaxis with tobramycin and colistin prior to colorectal surgery. In all patients, serum tobramycin concentrations were below the detection limit (0.3 mg/liter), implying a low risk of toxicity

Events and outcome.

<p>Illustration of event type and its outcome, complication or not. N = number+ = actual complication found − = no complication found.</p

Event and complications.

<p>Description of complication type when found. N = number % = percentage of events/complications.</p

Effects of CRP and SOFA on the odds of an event or complications.

<p>Effects of CRP and SOFA on the odds of an event or complications.</p

The Sequential Organ Failure Assessment Score.

<p>To define the SOFA score, biochemistry data and clinical parameters of patients were collected at 5 o’clock a.m. during routine controls on the Intensive care unit.</p>1<p>Adrenergic agents administered at least in hour (dose given are in µg/kg·min).</p