Validation of a Prospective Urinalysis-Based Prediction Model for the Outcome of COVID-19 Disease: A Multicenter Cohort Study

Background: Identifying preventive strategies in Covid-19 patients will help to improve resource-allocation and reduce mortality. In this Journal, we recently demonstrated in a post-mortem cohort that SARS-CoV-2 renal tropism was associated with kidney injury, disease severity and mortality. We also proposed an algorithm to predict the risk of adverse outcomes in Covid-19 patients harnessing urinalysis and protein/coagulation parameters on admission for signs of kidney injury. Here, we aimed to validate this hypothesis in a multicenter cohort. Methods: Patients hospitalized for Covid-19 at four tertiary centers were screened for an available urinalysis, serum albumin (SA) and antithrombin-III activity (AT-III) obtained prospectively within 48h upon admission. The respective presumed risk for an unfavorable course was categorized as “low”, “intermediate” or “high”, depending on a normal urinalysis, an abnormal urinalysis with SA ≥2 g/dl and AT-III ≥70%, or an abnormal urinalysis with at least one SA or AT-III abnormality. Time to ICU or death within ten days served as primary, in-hospital mortality and required organ support served as secondary endpoints. Findings: Among a total of N=223 screened patients, N=145 were eligible for enrollment, falling into the low (N=43), intermediate (N=84), and high risk (N=18) categories. The risk for ICU transfer or death was 100% in the high risk group and significantly elevated in the composite of high and intermediate risk as compared to the low risk group (63·7% vs. 27·9%; HR 2·6; 95%-CI 1·4 to 4·9; P=0·0020). Having an abnormal urinalysis was associated with mortality, need for mechanical ventilation, extra-corporeal membrane oxygenation (ECMO) or renal replacement therapy (RRT). Interpretation: Our data confirm that Covid-19-associated urine abnormalities on admission predict disease aggravation. This supports the conceptual relevance of Covid-19-associated kidney injury. By engaging a simple urine dipstick our algorithm allows for early preventive measures and appropriate patient stratification. Trial Registration: (ClinicalTrials.gov number NCT04347824) Funding Statement: This work was supported by the DFG (GR 1852/6-1 to OG; CRC1192 to JET, EH and TBH), (HU 1016/8-2, HU 1016/11-1, HU 1016/ 12-1 to TBH) and (GR 1852/6-1 to OG); by the BMBF (STOP-FSGS-01GM1518C and NephrESA-031L0191E to TBH), by the Else-Kroner Fresenius Foundation (Else Kroner-Promotionskolleg –iPRIME to TBH), and by the H2020-IMI2 consortium BEAt-DKD (115974 to TBH). In addition, the UMG Gottingen applied for Government funding (Covid-19 program) by The German Federal Ministry of Education and Research and the application currently is under consideration. Declaration of Interests: All authors report no conflict of interest in relation to this observational cohort-study. Ethics Approval Statement: According to the German Medicines Act, the study was approved by the leading institutional review board (IRB) of the UMG Gottingen (41/4/20), and all others.