Serum Uric Acid Concentrations and Risk of Adverse Outcomes in Patients With COVID-19

Abstract

Background: Although hyperuricemia frequently associates with respiratory diseases, patients with severe coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) can show marked hypouricemia. Previous studies on the association of serum uric acid with risk of adverse outcomes related to COVID-19 have produced contradictory results. The precise relationship between admission serum uric acid and adverse outcomes in hospitalized patients is unknown.

Methods: Data of patients affected by laboratory-confirmed COVID-19 and admitted to Leishenshan Hospital were retrospectively analyzed. The primary outcome was composite and comprised events, such as intensive care unit (ICU) admission, mechanical ventilation, or mortality. Logistic regression analysis was performed to explore the association between serum concentrations of uric acid and the composite outcome, as well as each of its components. To determine the association between serum uric acid and in-hospital adverse outcomes, serum uric acid was also categorized by restricted cubic spline, and the 95% confidence interval (CI) was used to estimate odds ratios (OR).

Results: The study cohort included 1854 patients (mean age, 58 years; 52% women). The overall mean ± SD of serum levels of uric acid was 308 ± 96 µmol/L. Among them, 95 patients were admitted to ICU, 75 patients received mechanical ventilation, and 38 died. In total, 114 patients reached composite end-points (have either ICU admission, mechanical ventilation or death) during hospitalization. Compared with a reference group with estimated baseline serum uric acid of 279-422 µmol/L, serum uric acid values ≥ 423 µmol/L were associated with an increased risk of composite outcome (OR, 2.60; 95% CI, 1.07- 6.29) and mechanical ventilation (OR, 3.01; 95% CI, 1.06- 8.51). Serum uric acid ≤ 278 µmol/L was associated with an increased risk of the composite outcome (OR, 2.07; 95% CI, 1.18- 3.65), ICU admission (OR, 2.18; 95% CI, 1.17- 4.05]), and mechanical ventilation (OR, 2.13; 95% CI, 1.06- 4.28), as assessed by multivariate analysis.

Conclusions: This study shows that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped. In particular, we found that compared with baseline serum uric acid levels of 279-422 µmol/L, values ≥ 423 µmol/L were associated with an increased risk of composite outcome and mechanical ventilation, whereas levels ≤ 278 µmol/L associated with increased risk of composite outcome, ICU admission and mechanical ventilation.

Keywords: COVID-19; U-shape; adverse outcome; relationship; uric acid.

Figure 1

Distribution of males, females and whole population of COVID-19 patients reaching the composite outcome, ICU admission, mechanical ventilation, or death relatively to uric acid concentrations. Distribution of patients’ outcomes in the three ranges of serum uric acid concentrations from low to high (UA ≤ 278 μmol/L, UA 279–422 μmol/L, ≥ 423 μmol/L). ICU, intensive care unit; MV, mechanical ventilation.

Figure 2

U-shaped association between uric acid concentrations and composite outcome, ICU admission, mechanical ventilation and death. Restricted multivariable cubic spline plots show U-shaped associations between admission serum uric acid and composite outcome (A), ICU admission (B), mechanical ventilation (C), and death (D). OR were adjusted for age, sex, hypertension, diabetes, lung disease, creatine, lymphocyte and platelet counts, aspartate aminotransferase, total bilirubin, albumin, creatine, C-reactive protein and D-dimer values. Median uric acid concentrations (279–422 μmol/L) have been considered as reference. Shaded areas are 95% CI derived from restricted cubic spline regressions with three spaced knots at the 5th, 50th, and 95th percentiles. The dashed line indicates OR equal to 1. ICU, intensive care unit; MV, mechanical ventilation.