Urinalysis parameters for predicting severity in coronavirus disease 2019 (COVID-19)

Graziella Bonetti 1 , Filippo Manelli 2 , Alessandra Bettinardi 1 , Gianluca Borrelli 1 , Gianfranco Fiordalisi 1 , Antonio Marino 1 , Annamaria Menolfi 1 , Sara Saggini 1 , Roberta Volpi 1 , Riccardo Adamini 3  and Giuseppe Lippi 4
  • 1 Laboratory of Clinical Pathology, ASST-Valcamonica, Esine, Brescia, Italy
  • 2 Emergency Department, ASST-Valcamonica, Esine, Brescia, Italy
  • 3 Department of Mechanical and Industrial Engineering, University of Brescia, Brescia, Italy
  • 4 Section of Clinical Biochemistry, University of Verona, Verona, Italy
Graziella Bonetti, Filippo Manelli, Alessandra Bettinardi, Gianluca Borrelli, Gianfranco Fiordalisi, Antonio Marino, Annamaria Menolfi, Sara Saggini, Roberta Volpi, Riccardo Adamini
  • Department of Mechanical and Industrial Engineering, University of Brescia, Brescia, Italy
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and Giuseppe Lippi

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 [1]. 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 [2], 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 [3], 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.

Table 1:

Urinalysis data in urine samples collected at emergency department admission in 226 patients who have been diagnosed with coronavirus disease 2019 (COVID-19).

ParameterResults
Median pH (IQR)6.0 (5.5–6.5)
Median SW (IQR)1.022 (1.019–1.026)
Protein presence203/226 (89.8%)
Blood presence163/226 (72.1%)
Urinary sediment
 WBC184/226 (81.4%)
 RBC159/226 (70.4%)
 Bacteria45/226 (19.9%)
 Casts111/226 (49.1%)
 Hyaline59/226 (26.1%)
 Granular15/226 (6.6%)
 Hyaline-granular72/226 (31.9%)
 Leucocytes1/226 (0.4%)
 Epithelial4/226 (1.8%)

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%).

Table 2:

Comparison of urinalysis data in urine samples collected at emergency department admission in patients who have been diagnosed with coronavirus disease 2019 (COVID-19), divided according to clinical outcome.

ParameterIn-hospital death (n=20)Discharged (n=25)p-Value
Age, years73.5 (64.5–79.0)64.0 (56.3–71.5)0.005
Plasma creatinine >URL16 (80%)5 (20%)<0.001
Plasma urea >URL15 (75%)6 (24%)0.001
eGFR <60, mL/min per 1.73 m26 (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
Protein
 Negative0 (0.0%)1 (4.0%)0.371
 ± and 18 (40.0%)14 (56.0%)0.291
 +2 and +412 (60.0%)10 (40.0%)0.187
Blood
 Negative5 (25.0%)4 (16.0%)0.458
 ± and 19 (45.0%)18 (72.0%)0.069
 +2 and +46 (30.0%)3 (12.0%)0.138
Urinary sediment
 Mucus2 (10%)10 (40%)0.025
 Bacteria6 (30%)6 (24%)0.655
 WBC15 (75%)17 (68%)0.611
 Negative9 (45%)7 (80%)0.242
 <20 by optic field11 (55%)16 (64%)0.545
 ≥20 by optic field0 (0%)2 (8%)0.201
 RBC
 Negative6 (30%)6 (24%)0.655
 <20 by optic field12 (60%)17 (68%)0.582
 ≥20 by optic field2 (10%)2 (8%)0.817
 Tubular cells8 (40.0%)3 (12.0%)0.032
 Urothelial cells3 (15.0%)2 (8%)0.463
 Hyaline casts9 (45%)5 (25%)0.075
 Hyaline-granular casts6 (30%)6 (24%)0.652
 Granular casts12 (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.

Figure 1:
Figure 1:

SediMax images of urinary sediment in bright-field in COVID-19 patients at hospital admission.

In the left image are clearly visible hyaline and hyaline-granular casts. In the right image, a granular cast is present while a cluster of tubular cells is visible at the center of it.

Citation: Clinical Chemistry and Laboratory Medicine (CCLM) 2020; 10.1515/cclm-2020-0576

Taken together, these urinalysis findings in a population of Italian COVID-19 patients seem in keeping with data earlier published in a Chinese cohort [1], [4], thus confirming the frequent presence of proteinuria and hematuria in this infectious disease [1], [4]. 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 [3], and ultimately reaffirming the importance of laboratory testing in risk stratification of COVID-19 [5], [6].

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.

References

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    Liu R, Ma Q, Han H, Su H, Liu F, Wu K, et al. The value of urine biochemical parameters in the prediction of severity of COVID-19. Clin Chem Lab Med 2020. Doi: https://doi.org/10.1515/cclm-2020-0220.

    • PubMed
    • Export Citation
  • 2.

    World Health Organization. Coronavirus disease (COVID-19) outbreak situation. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed: 24 Apr 2020.

  • 3.

    Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. Int Urol Nephrol 2020. Doi: https://doi.org/10.1007/s11255-020-02451-9. [Epub ahead of print].

    • PubMed
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  • 4.

    Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020. Doi: https://doi.org/10.1016/j.kint.2020.03.005.

  • 5.

    Henry BM, de Oliveira MH, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020. Doi: https://doi.org/10.1515/cclm-2020-0369. [Epub ahead of print].

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    • Export Citation
  • 6.

    Lippi BonettiG, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med 2020. Doi: https://doi.org/10.1515/cclm-2020-0240. [Epub ahead of print].

    • PubMed
    • Export Citation

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  • 1.

    Liu R, Ma Q, Han H, Su H, Liu F, Wu K, et al. The value of urine biochemical parameters in the prediction of severity of COVID-19. Clin Chem Lab Med 2020. Doi: https://doi.org/10.1515/cclm-2020-0220.

    • PubMed
    • Export Citation
  • 2.

    World Health Organization. Coronavirus disease (COVID-19) outbreak situation. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed: 24 Apr 2020.

  • 3.

    Henry BM, Lippi G. Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. Int Urol Nephrol 2020. Doi: https://doi.org/10.1007/s11255-020-02451-9. [Epub ahead of print].

    • PubMed
    • Export Citation
  • 4.

    Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020. Doi: https://doi.org/10.1016/j.kint.2020.03.005.

  • 5.

    Henry BM, de Oliveira MH, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020. Doi: https://doi.org/10.1515/cclm-2020-0369. [Epub ahead of print].

    • PubMed
    • Export Citation
  • 6.

    Lippi BonettiG, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med 2020. Doi: https://doi.org/10.1515/cclm-2020-0240. [Epub ahead of print].

    • PubMed
    • Export Citation
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    SediMax images of urinary sediment in bright-field in COVID-19 patients at hospital admission.

    In the left image are clearly visible hyaline and hyaline-granular casts. In the right image, a granular cast is present while a cluster of tubular cells is visible at the center of it.