Project description:Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Instead, using plasma proteomes quantifying 302 plasma protein groups at 387 timepoints in 57 critically ill patients on invasive mechanical ventilation, we found 14 proteins that showed trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81, n=49). We tested the established predictor on an independent validation cohort (AUROC of 1.0, n=24). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care.
Project description:Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage and fatal outcomes. MicroRNAs (miRNAs) are detectable in blood, reflecting cell activation and tissue injury. We performed small RNA-Seq in healthy controls (N=11), non-severe (N=18) and severe (N=16) COVID-19 patients
Project description: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.
Project description: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.
Project description:IntroductionCritically ill Covid-19 pneumonia patients are likely to develop the sequence of acute pulmonary hypertension, right ventricular (RV) strain, and eventually RV failure due to known pathophysiology (endothelial inflammation plus thrombo-embolism) that promotes increased pulmonary vascular resistance and pulmonary artery pressure. This study aimed to investigate the occurrence of acute pulmonary hypertension (aPH) as per established trans-thoracic echocardiography (TTE) criteria in Covid-19 patients receiving intensive care and to explore whether short-term outcomes are affected by the presence of aPH.MethodsMedical records were reviewed for patients treated in the intensive care units at a tertiary university hospital over a month. The presence of aPH on the TTE was noted, and plasma NTproBNP and troponin were measured as markers of cardiac failure and myocardial injury, respectively. Follow-up data were collected 21 d after the performance of TTE.ResultsIn total, 26 of 67 patients (39%) had an assessed systolic pulmonary artery pressure of > 35 mmHg (group aPH), meeting the TTE definition of aPH. NTproBNP levels (median [range]: 1430 [102-30 300] vs. 470 [45-29 600] ng L-1 ; P = .0007), troponin T levels (63 [22-352] vs. 15 [5-407] ng L-1 ; P = .0002), and the 21-d mortality rate (46% vs. 7%; P < .001) were substantially higher in patients with aPH compared to patients not meeting aPH criteria.ConclusionTTE-defined acute pulmonary hypertension was frequently observed in severely ill Covid-19 patients. Furthermore, aPH was linked to biomarker-defined myocardial injury and cardiac failure, as well as an almost sevenfold increase in 21-d mortality.
Project description:ObjectiveTo survey the healthcare professionals' background and experiences from work with patients with COVID-19 in intensive care units (ICUs) during the first wave of the COVID-19 pandemic in Norway.DesignObservational cohort study.SettingCOVID-ICUs in 27 hospitals across Norway.ParticipantsHealthcare professionals (n=484): nurses (81%), medical doctors (9%) and leaders (10%), who responded to a secured, web-based questionnaire from 6 May 2020 to 15 July 2020.Primary and secondary measuresHealthcare professionals': (1) professional and psychological preparedness to start working in COVID-ICUs, (2) factors associated with high degree of preparedness and (3) experience of working conditions.ResultsThe age of the respondents was 44.8±10 year (mean±SD), 78% were females, 92% had previous ICU working experience. A majority of the respondents reported professional (81%) and psychological (74%) preparedness for working in COVID-ICU. Factors significantly associated with high professional preparedness for working in COVID-19-ICU in a multivariate logistic model were previous ICU work experience (p<0.001) and participation in COVID-ICU simulation team training (p<0.001). High psychological preparedness was associated with higher age (p=0.003), living with spouse or partner (p=0.013), previous ICU work experience (p=0.042) and participation in COVID-ICU simulation team training (p=0.001). Working with new colleagues and new professional challenges were perceived as positive in a majority of the respondents, whereas 84% felt communication with coworkers to be challenging, 46% were afraid of being infected and 82% felt discomfort in denying access for patient relatives to the unit. Symptoms of sweating, tiredness, dehydration, headache, hunger, insecurity, mask irritation and delayed toilet visits were each reported by more than 50%.ConclusionsHealthcare professionals working during the first wave of COVID-ICU patients in Norway were qualified and prepared, but challenges and potential targets for future improvements were present.Trial registration numberNCT04372056.
Project description:IntroductionTo avoid exposure to SARS-COV-2, healthcare professionals use personal protective equipment (PPE) while treating COVID-19 patients. Prior studies have revealed the adverse effects (AEs) of PPE on healthcare workers (HCWs); however, no review has focused on the AEs of PPE on HCWs in intensive care units (ICUs). This review aimed to identify the AEs of PPE on HCWs working in ICUs during the COVID-19 pandemic.MethodsA scoping review was conducted. MEDLINE, CINAHL, the World Health Organization (WHO) global literature on COVID-19, and Igaku-chuo-zasshi (a Japanese medical database), Google Scholar, medRxiv, and Health Research Board (HRB) open research were searched from January 25-28, 2021. The extracted data included author(s) name, year of publication, country, language, article title, journal name, publication type, study methodology, population, outcome, and key findings.ResultsThe initial search identified 691 articles and abstracts. Twenty-five articles were included in the analysis. The analysis comprised four key topics: studies focusing on PPE-related headache, voice disorders, skin manifestations, and miscellaneous AEs of PPE. The majority of AEs for HCWs in ICUs were induced by prolonged use of masks.ConclusionThe AEs of PPE among HCWs in ICUs included heat, headaches, skin injuries, chest discomfort, and dyspnea. Studies with a focus on specific diseases were on skin injuries. Moreover, many AEs were induced by prolonged use of masks.