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:ImportanceOne-year outcomes in patients who have had COVID-19 and who received treatment in the intensive care unit (ICU) are unknown.ObjectiveTo assess the occurrence of physical, mental, and cognitive symptoms among patients with COVID-19 at 1 year after ICU treatment.Design, setting, and participantsAn exploratory prospective multicenter cohort study conducted in ICUs of 11 Dutch hospitals. Patients (N = 452) with COVID-19, aged 16 years and older, and alive after hospital discharge following admission to 1 of the 11 ICUs during the first COVID-19 surge (March 1, 2020, until July 1, 2020) were eligible for inclusion. Patients were followed up for 1 year, and the date of final follow-up was June 16, 2021.ExposuresPatients with COVID-19 who received ICU treatment and survived 1 year after ICU admission.Main outcomes and measuresThe main outcomes were self-reported occurrence of physical symptoms (frailty [Clinical Frailty Scale score ≥5], fatigue [Checklist Individual Strength-fatigue subscale score ≥27], physical problems), mental symptoms (anxiety [Hospital Anxiety and Depression {HADS} subscale score ≥8], depression [HADS subscale score ≥8], posttraumatic stress disorder [mean Impact of Event Scale score ≥1.75]), and cognitive symptoms (Cognitive Failure Questionnaire-14 score ≥43) 1 year after ICU treatment and measured with validated questionnaires.ResultsOf the 452 eligible patients, 301 (66.8%) patients could be included, and 246 (81.5%) patients (mean [SD] age, 61.2 [9.3] years; 176 men [71.5%]; median ICU stay, 18 days [IQR, 11 to 32]) completed the 1-year follow-up questionnaires. At 1 year after ICU treatment for COVID-19, physical symptoms were reported by 182 of 245 patients (74.3% [95% CI, 68.3% to 79.6%]), mental symptoms were reported by 64 of 244 patients (26.2% [95% CI, 20.8% to 32.2%]), and cognitive symptoms were reported by 39 of 241 patients (16.2% [95% CI, 11.8% to 21.5%]). The most frequently reported new physical problems were weakened condition (95/244 patients [38.9%]), joint stiffness (64/243 patients [26.3%]) joint pain (62/243 patients [25.5%]), muscle weakness (60/242 patients [24.8%]) and myalgia (52/244 patients [21.3%]).Conclusions and relevanceIn this exploratory study of patients in 11 Dutch hospitals who survived 1 year following ICU treatment for COVID-19, physical, mental, or cognitive symptoms were frequently reported.
Project description:PurposeInformation regarding the use of lung ultrasound (LUS) in patients with Coronavirus disease 2019 (COVID-19) is quickly accumulating, but its use for risk stratification and outcome prediction has yet to be described. We performed the first systematic and comprehensive LUS evaluation of consecutive patients hospitalized with COVID-19 infection, in order to describe LUS findings and their association with clinical course and outcome.MethodsBetween 21/03/2020 and 04/05/2020, 120 consecutive patients admitted to the Tel Aviv Medical Center due to COVID-19, underwent complete LUS within 24 h of admission. A second exam was performed in case of clinical deterioration. LUS score of 0 (best)-36 (worst) was assigned to each patient. LUS findings were compared with clinical data.ResultsThe median baseline total LUS score was 15, IQR [7-20]. Baseline LUS score was 0-18 in 80 (67%) patients, and 19-36 in 40 (33%) patients. The majority had patchy pleural thickening (n = 100; 83%), or patchy subpleural consolidations (n = 93; 78%) in at least one zone. The prevalence of pleural thickening, subpleural consolidations and the total LUS score were all correlated with severity of illness on admission. Clinical deterioration was associated with increased follow-up LUS scores (p = 0.0009), mostly due to loss of aeration in anterior lung segments. The optimal cutoff point for LUS score was 18 (sensitivity = 62%, specificity = 74%). Both mortality and need for invasive mechanical ventilation were increased with baseline LUS score > 18 compared to baseline LUS score 0-18. Unadjusted hazard ratio of death for LUS score was 1.08 per point [1.02-1.16], p = 0.008; Unadjusted hazard ratio of the composite endpoint (death or need for invasive mechanical ventilation) for LUS score was 1.12 per point [1.05-1.2], p = 0.0008.ConclusionHospitalized patients with COVID-19, at all clinical grades, present with pathological LUS findings. Baseline LUS score strongly correlates with the eventual need for invasive mechanical ventilation and is a strong predictor of mortality. Routine use of LUS may guide patients' management strategies, as well as resource allocation in case of surge capacity.
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:We perform shotgun transcriptome sequencing of human RNA obtained from nasopharyngeal swabs of patients with COVID-19, and identify a molecular signature associated with disease severity
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.
Project description:Background In March 2020, Covid-19 secondary to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was declared a global pandemic. Methods This retrospective observational study included patients with Covid-19, managed in a single intensive care unit (ICU). We collected data on patient characteristics, laboratory and radiological findings and ICU management. Data are reported as median (interquartile range). Binary logistic regression modelling was used to identify variables at ICU admission associated with mortality. Results 85 patients (age 57.3 years [49.4–64.2], 75.3% male) were followed up for 34 days (26–40). The commonest comorbidities were hypertension (51.8%), obesity (48.7%), and type 2 diabetes (31.8%). Covid-19 presented with shortness of breath (89.4%), fever (82.4%), and cough (81.2%), first noted 8 days (6–10) prior to ICU admission. PaO2/FiO2-ratios at ICU admission were 8.28 kPa (7.04–11.7). Bilateral infiltrates on chest X-ray, lymphopenia, and raised C-reactive protein and ferritin were typical. 81.2% received invasive mechanical ventilation (IMV). Acute kidney injury occurred in 62.4% with renal replacement therapy required in 20.0%. By the end of the follow-up period, 44.7% had died, 30.6% had been discharged from hospital, 14.1% had been discharged from ICU but remained in hospital and 10.6% remained in ICU. ICU length of stay was 14 days (9–23). Age was the only variable at admission which was associated with mortality. PaO2/FiO2-ratio, driving pressure and peak ferritin and neutrophil count over the first 72-hours of IMV all correlated with mortality. Conclusions We report the clinical characteristics, ICU practices and outcomes of a South London cohort with Covid-19, and have identified factors which correlate with mortality. By sharing our insight, we hope to further understanding of this novel disease.