ABSTRACT
COV50, a urinary proteomic classifier, predicts disease progression and death from SARS-CoV-2 at early stage, suggesting it might predict pre-established vulnerability. This study investigated the value of COV50 in predicting non-COVID-19 associated death. Urinary proteomic data were extracted from the Human Urinary Proteome Database. In the ICU group (n=1719), an increase in the COV50 score of one unit resulted in a 20% higher relative risk of death (adj. HR 1.2 [95% CI 1.17-1.24]). The same increase in COV50 in non-ICU patients (n=7474) resulted in a higher relative risk of 61% (adj. HR 1.61 [95% CI 1.47-1.76]), in line with adjusted meta-analytic HR estimate of 1.55. A higher COV50 scoring was observed in frail patients (p<0.0001). The COV50 classifier is predictive of death, and is associated with frailty suggesting that it detects pre-existing vulnerability. These data may serve as basis for proteomics guided intervention, reducing the risk of death and frailty.
Subject(s)
COVID-19 , DeathABSTRACT
Introduction: The role of positive pressure ventilation, central venous pressure (CVP) and inflammation on the occurrence of acute renal failure (AKI) have been poorly described in mechanically ventilated patient secondary to Sars-Cov-2 infection (Covid-19).Methods This was a monocenter retrospective cohort study of consecutive ventilated COVID-19 patients admitted in a French surgical ICU between Mars 2020 et July 2020. Worsening renal function (WRF) was defined as development of a new AKI or a persistent AKI during the five days after mechanical ventilation initiation. We studied the association between WRF and ventilatory parameters including positive end pressure (PEEP), CVP, and leukocytes count.Results 57 patients were included, 12 (21%) presented WRF. Daily PEEP, 5 days mean PEEP and daily CVP values were not associated with occurrence of WRF. 5 days mean CVP was higher in the WRF group compared to patients without WRF (median 12 [IQR, 11–13] mmHg vs 10 [9–12] mmHg, p = 0.03). Multivariate models with adjustment on leukocytes and SAPS II confirmed the association between CVP value and risk of WRF, odd ratio: 1.97 (IC95: 1.12–4.33). Leukocytes count was also associated with occurrence of WRF (14.3 [11.3–17.5]) G/L in the WRF group vs 9.2 [8.1–11.1] G/L in the no-WRF group) (p = 0,002).Conclusion In Mechanically ventilated COVID-19 patients, PEEP levels did not appear to influence occurrence of WRF. High CVP levels and leukocytes count are associated with risk of WRF.
Subject(s)
COVID-19ABSTRACT
Background The SARS CoV-2 pandemic remains a worldwide challenge. The CRIT Cov U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression. Following the interim analysis demanded by the German government, the full dataset was analysed to consolidate findings and propose clinical applications. Methods In eight European countries, 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8 point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression, receiver operating curve analysis with comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalistion costs standardised across countries. Findings The entry WHO scores were 1-3, 4-5 and 6 in 445 (44,0%), 529 (52,3%), and 38 (3,8%) patients, of whom 119 died and 271 progressed. The standardised odds ratios associated with COV50 for death were 2,44 (95% CI, 2,05-2,92) unadjusted and 1,67 (1,34-2,07) if adjusted for sex, age, body mass index, comorbidities and baseline WHO score, and 1,79 (1,60-2,01) and 1,63 (1,40-1,90), respectively, for disease progression (p<0,0001 for all). The predictive accuracy of optimised COV50 thresholds were 74,4% (95% CI, 71,6-77,1) for mortality (threshold 0,47) and 67,4% (64,1-70,3) for disease progression (threshold 0,04). On top of covariables and the baseline WHO score, these thresholds improved AUCs from 0,835 to 0,853 (p=0,0331) and from 0,697 to 0,730 (p=0,0008) for death and progression, respectively. Of 196 ambulatory patients, 194 (99,0%) did not reach the 0,04 threshold. Earlier intervention guided by high-risk COV50 levels should reduce hospital days with cost reductions expressed per 1000 patient-days ranging from MEuro 1,208 (95% percentile interval, 1,035-1,406) at low risk (COV50 <0,04) to MEuro 4,503 (4,107-4,864) at high risk (COV50 above 0,04 and age above 65 years). Interpretation The urinary proteomic COV50 marker is accurate in predicting adverse COVID-19 outcomes. Even in mild-to-moderate PCR-confirmed infections (WHO scores 1-5), the 0,04 threshold justifies earlier drug treatment, thereby reducing hospitalisation days and costs.
Subject(s)
COVID-19 , DeathABSTRACT
In patients with critical or mild COVID19 (WHO stages 6-8 [n=53] and stages 1-3 [n=66]), 593 urinary peptides significantly affected by disease severity were identified, reflecting the molecular pathophysiology associated with the course of the infection. The peptide profiles were similar compared with those observed in kidney disease, a prototype of target organ damage with major microvascular involvement, thereby confirming the observation that endothelial damage is a hallmark of COVID19. The clinical corollary is that COVID19 is an indication for anti-oxidative, anti-inflammatory and immunosuppressive treatment modalities protecting the endothelial lining.