scholarly journals SARS-CoV-2 RNAemia and proteomic biomarker trajectory inform prognostication in COVID-19 patients admitted to intensive care

Author(s):  
Manuel Mayr ◽  
Clemens Gutmann ◽  
Kaloyan Takov ◽  
Sean Burnap ◽  
Bhawana Singh ◽  
...  

Abstract Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia was associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Clemens Gutmann ◽  
Kaloyan Takov ◽  
Sean A. Burnap ◽  
Bhawana Singh ◽  
Hashim Ali ◽  
...  

AbstractPrognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified ‘Age, RNAemia’ and ‘Age, PTX3’ as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro.


Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 386
Author(s):  
Alice G. Vassiliou ◽  
Edison Jahaj ◽  
Ioannis Ilias ◽  
Vassiliki Markaki ◽  
Sotirios Malachias ◽  
...  

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Raphael Romano Bruno ◽  
Bernhard Wernly ◽  
Behrooz Mamandipoor ◽  
Richard Rezar ◽  
Stephan Binnebössel ◽  
...  

Purpose: Old (&gt;64 years) and very old (&gt;79 years) intensive care patients with sepsis have a high mortality. In the very old, the value of critical care has been questioned. We aimed to compare the mortality, rates of organ support, and the length of stay in old vs. very old patients with sepsis and septic shock in intensive care.Methods: This analysis included 9,385 patients, from the multi-center eICU Collaborative Research Database, with sepsis; 6184 were old (aged 65–79 years), and 3,201 were very old patients (aged 80 years and older). A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of ICU mortality. A sensitivity analysis in septic shock patients (n = 1054) was also conducted.Results: In the very old patients, the median length of stay was shorter (50 ± 67 vs. 56 ± 72 h; p &lt; 0.001), and the rate of a prolonged ICU stay was lower (&gt;168 h; 9 vs. 12%; p &lt; 0.001) than the old patients. The mortality from sepsis was higher in very old patients (13 vs. 11%; p = 0.005), and after multi-variable adjustment being very old was associated with higher odds for ICU mortality (aOR 1.32, 95% CI 1.09–1.59; p = 0.004). In patients with septic shock, mortality was also higher in the very old patients (38 vs. 36%; aOR 1.50, 95% CI 1.10–2.06; p = 0.01).Conclusion: Very old ICU-patients suffer from a slightly higher ICU mortality compared with old ICU-patients. However, despite the statistically significant differences in mortality, the clinical relevance of such minor differences seems to be negligible.


2020 ◽  
Vol 20 (S14) ◽  
Author(s):  
Pete Yeh ◽  
Yiheng Pan ◽  
L. Nelson Sanchez-Pinto ◽  
Yuan Luo

Abstract Background Increased chloride in the context of intravenous fluid chloride load and serum chloride levels (hyperchloremia) have previously been associated with increased morbidity and mortality in select subpopulations of intensive care unit (ICU) patients (e.g patients with sepsis). Here, we study the general ICU population of the Medical Information Mart for Intensive Care III (MIMIC-III) database to corroborate these associations, and propose a supervised learning model for the prediction of hyperchloremia in ICU patients. Methods We assessed hyperchloremia and chloride load and their associations with several outcomes (ICU mortality, new acute kidney injury [AKI] by day 7, and multiple organ dysfunction syndrome [MODS] on day 7) using regression analysis. Four predictive supervised learning classifiers were trained to predict hyperchloremia using features representative of clinical records from the first 24h of adult ICU stays. Results Hyperchloremia was shown to have an independent association with increased odds of ICU mortality, new AKI by day 7, and MODS on day 7. High chloride load was also associated with increased odds of ICU mortality. Our best performing supervised learning model predicted second-day hyperchloremia with an AUC of 0.76 and a number needed to alert (NNA) of 7—a clinically-actionable rate. Conclusions Our results support the use of predictive models to aid clinicians in monitoring for and preventing hyperchloremia in high-risk patients and offers an opportunity to improve patient outcomes.


2020 ◽  
Vol 22 (3) ◽  
pp. 388-396
Author(s):  
Dhouha Maamer ◽  
Ahlem Trifi ◽  
Mohamed Kacem Ben Fradj ◽  
Foued Daly ◽  
Mohamed Bassem Hammami ◽  
...  

Introduction: Patients in intensive care units (ICUs) are at high risk of unfavorable outcomes. Considering the role of vitamin D (Vit D) in cardiovascular and immune functions, Vit D deficiency could affect ICU patients’ outcomes. This study aimed to evaluate Vit D status and its predictive value for outcome in ICU patients. Patients and Methods: A total of 169 ICU patients were followed during ICU stay. Primary outcome was the occurrence of at least one major adverse event; secondary outcomes were organ failure, septic shock, ICU-acquired infection, other adverse events, and ICU mortality. Plasma 25-hydroxyvitamin D (25(OH)D) was assessed by immunoassay. Multivariate Cox regression analyses were performed to test the associations of low 25(OH)D levels with poor outcomes. Results: Around 75% of patients had 25(OH)D levels <12 ng/ml. During their ICU stay, 114 patients experienced a major adverse event, 85 patients presented an ICU-acquired infection, and 22 patients died. Plasma 25(OH)D levels <12 ng/ml were associated with higher risk of major adverse events, Hazard ratio [95% CI], 4.47 [1.77, 11.3], p = .020, and ICU-acquired infection, 2.67 [1.01, 7.42], p = .049, but not with increased risk of ICU mortality. Conclusions: Hypovitaminosis D is very common in ICU patients. Results of the present study show that low plasma 25(OH)D levels are associated with increased risk of unfavorable outcomes in these patients. Additional research is needed to investigate the impact of Vit D status and effect of Vit D supplementation in ICU patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kosuke Kuroda ◽  
Kenzo Ishii ◽  
Yuko Mihara ◽  
Naoya Kawanoue ◽  
Hidenori Wake ◽  
...  

AbstractVarious biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n = 16) than in survivors (n = 83) (median, 15.1 [interquartile ranges, 12.7–16.6] vs. 30.6 [22.1–39.6] µg/ml; p < 0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p < 0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Kirstine K. Søgaard ◽  
Veronika Baettig ◽  
Michael Osthoff ◽  
Stephan Marsch ◽  
Karoline Leuzinger ◽  
...  

Abstract Objectives SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. Methods We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for < 24 h (n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections. Results In the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4–74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8–18) and time to bloodstream infection 14 days (IQR, 6–30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients. Conclusions Community-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.


Perfusion ◽  
2020 ◽  
pp. 026765912098222
Author(s):  
Yu Wang ◽  
Tengfei Qiao ◽  
Jun Zhou

Purpose: Type A acute aortic dissection (AAD) is an uncommon catastrophic cardiovascular disease with high pre-hospital mortality rate without timely and effectively treated. The aim of this study was to assess the value of serum platelet to hemoglobin (PHR) in predicting in-hospital mortality in type A AAD patients. Methods: A total of 183 type A AAD patients were included in this retrospective investigation from January 2017 to December 2019. Admission blood routine parameters were gathered and PHR was computed. The outcome was all-cause in-hospital mortality within 30 days. Results The average levels of serum PHR were significant higher in survivor group than those in non-survivor group (1.14 ± 0.57 vs 0.87 ± 0.47, p = 0.006) and serum PHR was an independent factor associated with in-hospital mortality (hazard ratio (HR): 2.831; 95% confidence interval (CI): 1.108–7.231; p = 0.030). ROC noted that 0.8723 was chosen as the ideal cutoff value with a sensitivity of 64.3% and specificity of 72.5%. In addition, the area under the ROC curve (AUC) was 0.693 (95% CI 0.599–0.787, p < 0.001). Conclusion: Admission serum PHR can be used as an independent predictor of in-hospital mortality in patients with type A AAD.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stephanie-Susanne Stecher ◽  
Sofia Anton ◽  
Alessia Fraccaroli ◽  
Jeremias Götschke ◽  
Hans Joachim Stemmler ◽  
...  

Abstract Background Point-of-care lung ultrasound (LU) is an established tool in the first assessment of patients with coronavirus disease (COVID-19). Purpose of this study was to evaluate the value of lung ultrasound in COVID-19 intensive care unit (ICU) patients in predicting clinical course and outcome. Methods We analyzed lung ultrasound score (LUS) of all COVID-19 patients admitted from March 2020 to December 2020 to the Internal Intensive Care Unit, Ludwig-Maximilians-University (LMU) of Munich. LU was performed according to a standardized protocol at ICU admission and in case of clinical deterioration with the need for intubation. A normal lung scores 0 points, the worst LUS has 24 points. Patients were stratified in a low (0–12 points) and a high (13–24 points) lung ultrasound score group. Results The study included 42 patients, 69% of them male. The most common comorbidities were hypertension (81%) and obesity (57%). The values of pH (7.42 ± 0.09 vs 7.35 ± 0.1; p = 0.047) and paO2 (107 [80–130] vs 80 [66–93] mmHg; p = 0.034) were significantly reduced in patients of the high LUS group. Furthermore, the duration of ventilation (12.5 [8.3–25] vs 36.5 [9.8–70] days; p = 0.029) was significantly prolonged in this group. Patchy subpleural thickening (n = 38; 90.5%) and subpleural consolidations (n = 23; 54.8%) were present in most patients. Pleural effusion was rare (n = 4; 9.5%). The median total LUS was 11.9 ± 3.9 points. In case of clinical deterioration with the need for intubation, LUS worsened significantly compared to baseline LU. Twelve patients died during the ICU stay (29%). There was no difference in survival in both LUS groups (75% vs 66.7%, p = 0.559). Conclusions LU can be a useful monitoring tool to predict clinical course but not outcome of COVID-19 ICU patients and can early recognize possible deteriorations.


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