Association of Serum Uric Acid Levels with COVID-19 Severity

Abstract Aims: Hyperuricemia has attracted increasing attention, however, limited attention has been paid to the potential dangers of lowering serum uric acid (SUA). We observed lower levels of SUA in COVID-19 patients. Therefore, we aim to explore the SUA levels in COVID-19 patients and the relationship between SUA and the severity of COVID-19. Methods: A case-control study based on 91 cases with COVID-19 and 1:3 age- and sex-matched healthy control subjects (N=273) were included. We firstly compared the SUA levels and the uric acid/creatinine (UA/Cr) ratio between COVID-19 patients and the healthy controls. Then, we examined the association of the SUA levels and UA/Cr ratios with COVID-19 severity defined according to the fifth edition of China’s Diagnosis and Treatment Guidelines of COVID-19. Results: SUA levels at admission were 2.59% lower, UA/Cr ratios 6.06% lower in COVID-19 patients compared to controls. In sex stratified analysis, SUA and UA/Cr were lower in male COVID-19 patients while only SUA was lower in female COVID-19 patient. Moreover, SUA and UA/Cr values were 4.27% and 8.23% lower in the severe group than in the moderate group among male COVID patients. A multiple linear regression analysis showed that SARS-CoV-2 infection and male sex were independent factors associated with lower SUA levels. COVID-19 male patients with low SUA levels at had higher risk of developing severe symptoms than those with high SUA levels (incidence rate ratio: 4.05; 95% CI:1.11，14.72) at admission. After completion of the first follow-up of the COVID-19 patients within 1-3 weeks after discharge, we found that male patients experienced severe symptoms had significantly lower SUA and UA/Cr ratio levels comparing to moderate patients but no significant difference between different time points. In females, female patients have both SUA and UA/Cr ratio levels lower at discharge than that at admission, however these differences disappear at follow-up exam.Conclusion: COVID-19 patients had SUA and UA/Cr values lower than normal at admission. Male COVID-19 patients with low SUA levels had a significantly higher risk of developing severe symptoms than those with high SUA levels. During the aggravation course of the disease, the level of SUA gradually decreased until discharge. At follow-up exam, the level of SUA is similar to the levels at admission.