Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a cohort study

BackgroundThe 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. MethodsIn 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. FindingsThe entry WHO scores were 1-3, 4-5 and 6 in 445 (44{middle dot}0%), 529 (52{middle dot}3%), and 38 (3{middle dot}8%) patients, of whom 119 died and 271 progressed. The standardised odds ratios associated with COV50 for death were 2{middle dot}44 (95% CI, 2{middle dot}05-2{middle dot}92) unadjusted and 1{middle dot}67 (1{middle dot}34-2{middle dot}07) if adjusted for sex, age, body mass index, comorbidities and baseline WHO score, and 1{middle dot}79 (1{middle dot}60-2{middle dot}01) and 1{middle dot}63 (1{middle dot}40-1{middle dot}90), respectively, for disease progression (p<0{middle dot}0001 for all). The predictive accuracy of optimised COV50 thresholds were 74{middle dot}4% (95% CI, 71{middle dot}6-77{middle dot}1) for mortality (threshold 0{middle dot}47) and 67{middle dot}4% (64{middle dot}1-70{middle dot}3) for disease progression (threshold 0{middle dot}04). On top of covariables and the baseline WHO score, these thresholds improved AUCs from 0{middle dot}835 to 0{middle dot}853 (p=0{middle dot}0331) and from 0{middle dot}697 to 0{middle dot}730 (p=0{middle dot}0008) for death and progression, respectively. Of 196 ambulatory patients, 194 (99{middle dot}0%) did not reach the 0{middle dot}04 threshold. Earlier intervention guided by high-risk COV50 levels should reduce hospital days with cost reductions expressed per 1000 patient-days ranging from M{euro} 1{middle dot}208 (95% percentile interval, 1{middle dot}035-1{middle dot}406) at low risk (COV50 <0{middle dot}04) to M{euro} 4{middle dot}503 (4{middle dot}107-4{middle dot}864) at high risk (COV50 [≥]0{middle dot}04 and age [≥]65 years). InterpretationThe 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{middle dot}04 threshold justifies earlier drug treatment, thereby reducing hospitalisation days and costs. FundingGerman Federal Ministry of Health acting upon a decree from the German Federal Parliament.

Critical COVID-19 represents an endothelial disease with high similarity to kidney disease on the molecular level

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.