Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases

Abstract

Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning.

Objectives: To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening.

Design: Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed.

Setting and participants: Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period.

Main outcomes and measures: The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data.

Results: Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%.

Conclusions and relevance: Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

Conflict of interest statement

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

Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.

Figures

Figure 1.

Flow chart of patient enrollment. Five hundred one cases recruited at National Center for Global Health and Medicine (NCGM) were evaluated and merged with the Yamanashi Prefectural Central Hospital (YPCH) cohort. After exclusion of cases that failed to meet inclusion criteria, 224 cases were available for analysis. Hsp. = hospital, JPN = Japan, POC = point of care, L-FABP = L-type fatty acid-binding protein.

Figure 2.

Progression of disease severity and urinary L-type fatty acid-binding protein (L-FABP) level at admission. The same patients are plotted in the same position at both time points. Shapes of symbols indicate severity 1 wk later (severe, circles; moderate, squares; mild, triangles). Symbol color reflects severity at all time points (severe, red; moderate, blue; mild, green). Green and red lines are cutoff values of L-FABP calculated from the receiver operating characteristic analysis. The timepoint 1 wk later is equivalent to 10 d after the onset of COVID-19 in this study. A, Urinary L-FABP (unadjusted) in initially mild cases measured by either enzyme-linked immunosorbent assay (ELISA) or Biochemistry analyzer. B, Urinary adjusted L-FABP in initially mild cases measured by either ELISA or Biochemistry analyzer. C, Urinary L-FABP (unadjusted) in all cases measured by either ELISA or Biochemistry analyzer. D, Urinary adjusted L-FABP in all cases measured by either ELISA or Biochemistry analyzer. E, Urinary L-FABP point of care (POC) quantitated by the specific reader in initially mild cases excluding pneumonia by simple CT scan for lung field. TL = Test Line intensity.