To the Editor,
We read with interest the recent article by Liu et al., who described the clinical significance of urinalysis for predicting the severity of coronavirus disease 2019 (COVID-19) in a group of 119 Chinese patients . It is now undeniable that the managed care of patients with COVID-19, which has recently been upgraded to a pandemic disease by the World Health Organization (WHO) after causing over 200,000 deaths worldwide , encompasses the identification of clinical and laboratory parameters, enabling accurate risk stratification of progressing toward severe or critical disease.
As it has now been clearly established that urinary tract involvement is commonplace in patients with COVID-19, and that progressive deterioration of renal function shall be considered an unfavorable prognostic factor , we present here the first report of urinalysis abnormalities in a series of COVID-19 Italian patients admitted to the emergency department (ED) of Valcamonica Hospital of Esine, between March 13 and April 8, 2020.
The study population of this retrospective observational investigation consisted of 226 patients consecutively admitted to the local ED for COVID-19. Disease diagnosis was based on current standards, thus encompassing suggestive findings on chest computed tomography (CT) and positive results of real-time reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 on oropharyngeal and nasopharyngeal swabs. Overall, 154 of our patients were male (median age, 66 years; interquartile range [IQR], 57–75 years), whilst 72 were female (median age, 69 years; IQR, 57–76 years). Urinalysis was carried out in the local laboratory with the Aution Max AX-4030 (Arkray, Kyoto, Japan) and SediMax (Menarini, Firenze, Italy) systems, using proprietary reagents, whilst microscopic assessment was performed when necessary, according to results of biochemical urinalysis. Exclusion criteria were past history of diabetes and kidney disease. From the initial group of 226 patients, 51 were immediately discharged from the ED after results of chest CT, showing non-severe disease, whilst the remaining 175 patients were hospitalized. From this group of patients, 45 were selected for inclusion, divided into two groups, the former including 20 patients who died during hospital stay and the latter encompassing 25 patients who displayed clinical improvement and could hence be discharged. The remaining 130 patients were still hospitalized at the time of writing this report, so no final information on disease outcome had become available.
The results of urinalysis in all the 226 COVID-19 patients originally admitted to the local ED are shown in Table 1. Cumulatively, proteinuria and hematuria were present in most patients, already at ED admission. The analysis of the urine sediment also revealed the presence of erythrocytes and casts in nearly half of all patients.
|Median pH (IQR)||6.0 (5.5–6.5)|
|Median SW (IQR)||1.022 (1.019–1.026)|
|Protein presence||203/226 (89.8%)|
|Blood presence||163/226 (72.1%)|
Results are reported as number and % of patients with pathological data on the total number of 226 urinary samples collected at the emergency department unless otherwise specified. Presence: if ≥1 element/hpf is present. Absence: no element is visible in one of the 20 optic fields of SediMax images. IQR, interquartile range; RBC, red blood cells; WBC, white blood cells.
The comparison of urinalysis in the two study cohorts (i.e. in patients who died or in those who could be discharged) is shown in Table 2. Notably, most urinalysis parameters were not found to be substantially different in patients who died during hospital stay and those who could be discharged, though some interesting aspects can be highlighted. One paradigmatic feature was the more frequent presence of granular cylinders and tubular cells in the urine of patients who died, as also shown in Figure 1. Renal impairment was also found to be more frequent in patients who died compared to those who could be discharged. This is clearly reflected by the higher rate of abnormal urea and creatinine values at admission in patients who died (i.e. between 75% and 80%) compared to those who could be discharged (i.e. between 20% and 24%).
|Parameter||In-hospital death (n=20)||Discharged (n=25)||p-Value|
|Age, years||73.5 (64.5–79.0)||64.0 (56.3–71.5)||0.005|
|Plasma creatinine >URL||16 (80%)||5 (20%)||<0.001|
|Plasma urea >URL||15 (75%)||6 (24%)||0.001|
|eGFR <60, mL/min per 1.73 m2||6 (30.0%)||5 (20.0%)||0.443|
|Median pH (IQR)||5.75 (5.5–6.0)||6.0 (5.5–6.0)||0.889|
|Median SW (IQR)||1.022 (1.019–1.025)||1.022 (1.0187–1.0255)||0.670|
|Negative||0 (0.0%)||1 (4.0%)||0.371|
|± and 1||8 (40.0%)||14 (56.0%)||0.291|
|+2 and +4||12 (60.0%)||10 (40.0%)||0.187|
|Negative||5 (25.0%)||4 (16.0%)||0.458|
|± and 1||9 (45.0%)||18 (72.0%)||0.069|
|+2 and +4||6 (30.0%)||3 (12.0%)||0.138|
|Mucus||2 (10%)||10 (40%)||0.025|
|Bacteria||6 (30%)||6 (24%)||0.655|
|WBC||15 (75%)||17 (68%)||0.611|
|Negative||9 (45%)||7 (80%)||0.242|
|<20 by optic field||11 (55%)||16 (64%)||0.545|
|≥20 by optic field||0 (0%)||2 (8%)||0.201|
|Negative||6 (30%)||6 (24%)||0.655|
|<20 by optic field||12 (60%)||17 (68%)||0.582|
|≥20 by optic field||2 (10%)||2 (8%)||0.817|
|Tubular cells||8 (40.0%)||3 (12.0%)||0.032|
|Urothelial cells||3 (15.0%)||2 (8%)||0.463|
|Hyaline casts||9 (45%)||5 (25%)||0.075|
|Hyaline-granular casts||6 (30%)||6 (24%)||0.652|
|Granular casts||12 (60%)||2 (8%)||<0.001|
Statistical evaluation was performed by the χ2 test and by the Mann-Whitney test for independent samples for continuous variables; a p-value <0.05 or less was considered significant. Plasma creatinine reference interval, males: 55.4–90.8, females: 44.6–76.2 μmol/L and urea: 3.2–7.9 mmol/L for the Valcamonica population. eGFR, estimated glomerular filtration rate; IQR, interquartile range; RBC, red blood cells; SW, specific weight; URL, upper reference limit; WBC, white blood cells.
Taken together, these urinalysis findings in a population of Italian COVID-19 patients seem in keeping with data earlier published in a Chinese cohort , , thus confirming the frequent presence of proteinuria and hematuria in this infectious disease , . Nevertheless, the values of these urine parameters were found to be consistently higher than in previous studies, thus suggesting that our COVID-19 population was perhaps in worst clinical conditions at ED admission, as mirrored by the considerably high mortality in our setting (i.e. 26%). Another important aspect that emerged from this retrospective investigation is that renal involvement may be a significant predictor of unfavorable disease progression, thus confirming previous assumptions , and ultimately reaffirming the importance of laboratory testing in risk stratification of COVID-19 , .
We can hence conclude that urinalysis shall be regularly performed in all patients with COVID-19, whereby it may provide important information for clinical management and risk prediction.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Research funding: None declared.
Competing interests: Authors state no conflict of interest.
Ethical approval: The local Institutional Review Board deemed the study exempt from review.
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