ABSTRACT
Background Venous thromboembolism (VTE) contributes significantly to COVID-19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID-19. Whether suPAR levels identify patients with COVID-19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID-19 with suPAR and D-dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine-Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D-dimer levels. There was a positive association between suPAR and D-dimer (ß=7.34; P=0.002). Adjusted for clinical covariables, including D-dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51-4.75]; P<0.001). Findings were consistent when stratified by D-dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D-dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D-dimer in patients hospitalized for COVID-19. Combining suPAR and D-dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.
Subject(s)
COVID-19 , Venous Thromboembolism , Biomarkers , COVID-19/complications , Female , Humans , Male , Middle Aged , Receptors, Urokinase Plasminogen Activator , Urokinase-Type Plasminogen Activator , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiologyABSTRACT
SARS-CoV-2 can cause diverse severe and lasting damage to the kidneys. In the latest issue of Cell Stem Cell, Jansen et al. utilized data gleaned from human kidney autopsies and human induced pluripotent stem cell-derived kidney organoids to investigate the direct effects of SARS-CoV-2 infection on kidney cells. They found that such infections resulted in renal scarring (notably, tubulointerstitial fibrosis).