Serum uric acid, disease severity and outcomes in COVID-19

Abstract

Background The severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19. Methods In a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19. Results The discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50–168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6–7.8, P < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4–41.4, P < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules. Conclusions Among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.

Gout and the COVID-19 pandemic

“…Interestingly, observational studies of serum urate in patients with COVID-19 have demonstrated that the prevalence of hypouricemia increases following hospital admission for COVID-19 due to proximal renal tubule dysfunction. An inverse association between serum urate levels and disease severity has also been observed in these studies [18,19]. Further research in people with gout and COVID-19 infection are needed to understand whether serum urate levels decline during COVID-19 infection and whether this is associated with adverse outcomes.…”

Uric acid as a prognostic factor and critical marker of COVID-19

“…Therefore, the change in UA can help to judge the turning point of patients' condition. In a retrospective study using two independent cohorts, among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation 38 . However, a study cohort included 1854 patients showed that the association between admission serum uric acid and composite outcome of COVID-19 patients was U-shaped.…”

U-shaped association between abnormal serum uric acid levels and COVID-19 severity: reports from the Japan COVID-19 Task Force

“…Previous reports have described an association between high serum uric acid levels and COVID-19 severity, particularly mortality or the rate of using invasive mechanical ventilation (IMV) ( Ghazanfari et al, 2021 ;Zheng et al, 2021 ). However, researchers have also reported an association between low serum uric acid levels and COVID-19 severity ( Dufour et al, 2021 ;Werion et al, 2020 ). Some studies have shown a U-shaped association between serum uric acid levels and the risk of death ( Cho et al, 2018 ;Hu et al, 2020 ).…”