Cautious handling of urine from moderate to severe COVID-19 patients

To the Editor,

Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide.¹ Upper and lower respiratory tract specimens are screened using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to identify individuals infected with SARS-CoV-2. The virus has also been detected in other specimens, such as the blood, stool, and urine.2, 3, 4 Although the duration of SARS-CoV-2 viral shedding in the upper and lower respiratory tract and stool has been reported,5, 6, 7 limited data are available for that in the urine.

Here, we investigated the detectability and duration of SARS-CoV-2 RNA in the urine among patients with different severities of COVID-19.

Methods

From February 7, 2020 to March 24, 2020, we evaluated the presence of SARS-CoV-2 RNA in the urine of patients admitted to the National Center for Global Health and Medicine, a tertiary care institution in Tokyo, Japan. The patients had been diagnosed with COVID-19 by qRT-PCR using nasal or pharyngeal swab specimens.⁸ Information on demographics, comorbidities, disease severity, number of days from the onset of COVID-19 to the testing of urine, and qRT-PCR results in the urine (cycle threshold [Ct] values and viral load [VL] as virus copies/mL) were collected. Disease severity was defined as follows: a patient without oxygen demand, mild; a patient with oxygen demand, moderate; and a patient requiring a ventilator to treat respiratory failure, severe. The study protocol was approved by the institutional review board (approval no: NCGM-G-003472-02), and written informed consent for publication was obtained from each patient.

Results

Twenty-three specimens from 20 patients were collected (Table 1 ). The median age of this cohort was 49.5 years (range: 21–83 years), and 90.4% were men. According to the clinical course, 9 (45.0%), 8 (40.0%), and 3 (15.0%) patients had mild, moderate, and severe disease, respectively. The median number of days from the onset of COVID-19 to urine testing was 7 days (range: 2-28 days). One patient each with moderate and severe conditions tested positive for SARS-CoV-2 RNA in the urine. The proportions of patients with urine samples positive for SARS-CoV-2 RNA among the mild, moderate, and severe cases were 0 of 9 (0%), 1 of 8 (12.5%), and 1 of 3 (33.3%), respectively. Patient no. 12 (moderate) tested positive for SARS-CoV-2 RNA in the first urinalysis (Ct value: 38.6, VL: 840 copies/mL) but not at 3 days after the positive result. Patient no. 19 (severe) was admitted to the hospital on illness day (ID) 7 from onset and tested positive for the presence of SARS-CoV-2 RNA in the urine (Ct value: 38.7, VL: 800 copies/mL). During the clinical course, he developed severe pulmonary dysfunction on ID 9 and required intensive care, including a mechanical ventilator and venovenous extracorporeal membrane oxygenation. He remained positive for SARS-CoV-2 RNA in the urine on ID 11 (Ct value: 40.6, VL: 254 copies/mL). On ID 15, continuous renal replacement therapy was required. SARS-CoV-2 RNA was not detected in the urine on ID 17. Finally, the patient passed away on ID 45.

Table 1.

Patient demographics, comorbidities, disease severity, and results of SARS-CoV-2 qRT-PCR in urine

Patient No.	Age (years)	Sex	Race	Comorbidities	Severity	Days from disease onset to testing of urine	Hospital day	qRT-PCR in urine
1	21	Female	Asian	None	Mild	2	1	UND
2	70	Male	White	Dementia	Mild	2	2	UND
3	53	Male	White	None	Mild	4	1	UND
4	46	Male	Asian	DM	Mild	5	1	UND
5	62	Male	Asian	DL	Mild	6	1	UND
6	41	Male	Asian	None	Mild	7	8	UND
7	54	Male	Asian	None	Mild	11	10	UND
8	29	Male	Asian	None	Mild	13	1	UND
9	29	Female	Asian	None	Mild	28	19	UND
10	43	Male	Asian	None	Moderate	2	1	UND
11	53	Male	Asian	HTN, DL	Moderate	4	1	UND
12	53	Male	Asian	None	Moderate	5	4	Ct value: 38.6, VL: 840 copies/mL
						8	7	UND
13	31	Male	Asian	None	Moderate	10	1	UND
14	28	Male	Asian	None	Moderate	10	3	UND
15	44	Male	Asian	None	Moderate	11	8	UND
16	68	Male	Asian	Post kidney transplant, HTN, OMI	Moderate	15	1	UND
17	83	Male	Asian	HTN	Moderate	16	1	UND
18	63	Male	White	Obesity	Severe	6	1	UND
19	72	Male	Asian	DM, HTN	Severe	7	1	Ct value: 38.7, VL: 800 copies/mL
						11	5	Ct value: 40.6, `VL: 254 copies/mL
						17	11	UND
20	42	Male	Asian	HTN	Severe	9	3	UND

Ct, cycle threshold; DM, diabetes mellitus; HTN, hypertension; DL, dyslipidemia; OMI, old myocardial infarction; qRT-PCR, quantitative real-time polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome-coronavirus 2; UND, undetected; VL, viral load.

Discussion

During the study period, SARS-CoV-2 RNA was detected in the urine of two of 20 patients (10%). Only 2 previous reports have evaluated the presence of this virus in urine.^{2 , 3} In one study, the virus was detected in 1 of 9 patients (11.1%).²Another study examined urine specimens from 72 patients; however, no patients tested positive for SARS-CoV-2 RNA.³ Although these studies did not evaluate the severity of disease in the tested patients,we considered the severity of disease in patients who were positive for SARS-CoV-2 RNA. No patients with mild disease tested positive for SARS-CoV-2 RNA; however, one patient each in the moderate and severe groups had SARS-CoV-2 RNA in the urine. Thus, we showed that SARS-CoV-2 RNA could be excreted in the urine for at least 4 days. This duration is relatively short compared with those of other specimens, such as pharyngeal swabs (up to 30 days) and stools (14-18 days).4, 5, 6 COVID-19 transmission among health care workers has become a major problem worldwide⁸; thus, health care workers should carefully handle urine samples from patients with the moderate to severe disease.

There were several limitations to this study. First, because of the small number of patients enrolled, the relationship between clinical severity and SARS-CoV-2 RNA detection in the urine could not be established. Second, we did not evaluate the infectious potential of the virus in the urine. However, a previous study indicated that SARS-CoV-2 RNA isolated from urine might be infectious.⁹ An autopsy case suggesting direct infection of the renal tubular epithelium was also reported.¹⁰ Together, these reports indicate that SARS-CoV-2 RNA in the urine is infectious.

In conclusion, our results suggest that SARS-CoV-2 RNA may be excreted in the urine depending on the severity of COVID-19. Although the period of viral shedding in the urine is relatively short, HCWs should also take infection prevention and control measures when handling urine, particularly samples from patients with moderate to severe COVID-19.