Evaluation of Coronavirus Disease 2019 Severity Using Urine Biomarkers

Abstract

Subjects: Early detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019.

Interventions: Not applicable.

Measurements and main results: This is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary β2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (n = 12). Patients treated with oxygen were assigned to the moderate group (n = 13). Other patients were assigned to the mild group (n = 33). Urine tests revealed that low β2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were β2-microglobulin; severe versus moderate + mild: 2,457 μg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 μg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary β2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend.

Conclusions: Evaluating urinary biomarkers such as β2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.

Keywords: acute kidney injury; coronavirus disease 2019; cytokine; liver-type fatty acid-binding protein; urinary biomarker; β2-microglobulin.

Conflict of interest statement

The authors have disclosed that they do not have any potential conflicts of interest.

Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.

Figures

Figure 1.

Assessment of coronavirus disease 2019 severity using urine specimens within 10 d of onset. The distribution and clinical severity of sCre (A), urinary β2-microglobulin (β2MG) (B), urinary NAG (C), and urinary liver-type fatty acid-binding protein (L-FABP) (D) were presented in patients for whom we were able to obtain urine specimens within 10 d of disease onset (n = 49). Scatter plots plotting urinary β2MG on the horizontal axis and urinary L-FABP on the vertical axis allowed us to distinguish between severe, moderate, and mild illness (E). Patients with moderate disease but mild acute kidney injury at admission, or uncontrolled HIV, tended to have relatively high levels of β2MG and L-FABP. NAG = N-acetyl-β-d-glucosaminidase, sCre = serum creatinine.

Figure 2.

Receiver operating characteristic (ROC) curves for detecting mild or severe cases in coronavirus disease 2019. A–D, ROC curve analysis was performed to detect the mild and severe groups using urine tests. The resulting cutoff values were β2-microglobulin (β2MG); severe versus moderate + mild (A): 2,457 μg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve [AUC] 85.9%), severe + moderate versus mild (B): 2,457 μg/dL (specificity 87.5% and sensitivity 82.4%, AUC 84.4%), liver-type fatty acid-binding protein (L-FABP); severe versus moderate + mild (C): 22.0 μg/gCre (specificity 84.6% and sensitivity 90.0%, AUC 91.8%), severe + moderate versus mild (D): 9.0 μg/gCre (specificity 84.4% and sensitivity 94.1%, AUC 88.6%). E and F, Progression of disease severity and urinary biomarkers at admission. The same patient is plotted in the same position at both time points. Shape of symbols indicates the severity 1 wk later (severe, circle; moderate, square; mild, triangle). Symbol color is determined by the severity at each time point (severe, red; moderate, blue; mild, green). The green and red lines are the cutoff values of the biomarkers calculated from the ROC analysis.