Re: Jan-Niclas Mumm, Andreas Osterman, Michael Ruzicka, et al. Urinary Frequency as a Possible Overlooked Symptom in COVID-19 Patients: Does SARS-CoV-2 Cause Viral Cystitis? Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.05.013: Severe Involvement of the Urinary Tract During COVID-19 Infection.

Mumm et al [1] reported that urinary frequency might be a symptom of SARS-CoV-2. This assumption is based on the finding that the bladder urothelium, as well as the kidney, harbors cells expressing ACE2, the receptor for the viral spike protein [2], [3]. Our experience appears to confirm their suspicion, further suggesting that the urinary tract may become the target of life-threatening involvement by SARS-CoV-2.

We report three cases of gross hematuria admitted to two hospitals in Northern Italy between February 26 and March 29, 2020. The severity of hematuria greatly worsened after contracting symptomatic COVID-19 infection during hospitalization. Clinical and laboratory details are summarized in Table 1 . The clinical scenario in one representative patient is described.

Table 1

Reason for admission, pre-existing urologic condition, and characteristics of patients at the onset of COVID-19 symptoms

	Patient 1	Patient 2	Patient 3
Age (yr)	66	72	84
Sex	Male	Male	Male
Reason for admission	Hematuria, urinary retention	Hematuria	Hematuria
Urologic condition	Radiation cystitis	Benign prostate hyperplasia	Benign prostate hyperplasia
COVID-19 symptoms	Fever 38 °C, diarrhea	Fever 39 °C, cough	Fever 38 °C, cough
Time from exposure (d)	6–8	7	5
Oxygen saturation (%)	98	95	95
Radiography of chest	Normal	Bilateral opacities	Bilateral opacities
C-reactive protein (mg/l)	180	125	38
Procalcitonin (ng/ml)	2.0	0.05	0.37
White blood cells (/mm3)	3600	4700	3300
International normalized ratio	1.45	1.25	1.54
Serum creatinine (mg/dl)	1.3	0.9	1.4
Swab for COVID-19	Positive	Positive	Positive
Treatment of hematuria	Endoscopic	Embolization	Conservative
Respiratory support	Noninvasive ventilation	High-flow oxygen	High-flow oxygen
Anticoagulants	None	None	Low-dose aspirin

A 66-yr-old man (Patient 1) with a history of nonsevere radiation-induced hemorrhagic cystitis after radical prostatectomy and radiation therapy for pT3b prostate cancer in 2005 was admitted to an external hospital for recurring hematuria. On hospital day 23, after a course characterized by mild hematuria and anemia and negative abdominal computed tomography (CT), he developed hypotension and fever. A blood culture tested positive for a methicillin-resistant Staphyloccus aureus and repeat CT imaging showed a 3-cm renal abscess; systemic therapy with piperacillin/tazobactam was initiated. On hospital day 25, owing to worsening hematuria with severe anemia requiring multiple transfusions, the patient was transferred to the Department of Urology in a tertiary referral hospital. In addition to persisting hematuria and fever, the patient developed diarrhea. A chest X-ray was negative and his O2 saturation was 98%. A test to detect SARS-CoV-2 infection was positive. The patient was transferred to an intermediate care unit because of respiratory deterioration. After 3 wk of noninvasive ventilation, his laboratory and clinical parameters improved. Imaging confirmed that the renal abscess cleared following a 2-wk course of meropenem. The patient underwent cystoscopy with coagulation of bleeding foci. Biopsy of bladder tissue was consistent with radiation cystitis. He was discharged with clear urine.

Patients 2 and 3 were admitted for mild anemia and hematuria related to their benign prostate hyperplasia. Similarly, severe hematuria developed after the onset of symptomatic confirmed COVID-19, requiring multiple blood transfusions, prolonged bladder irrigation, and embolization of hypogastric arteries in one case.

Our experience suggests that SARS-CoV-2 can severely impair the urinary system. The time from suspected exposure to the onset of COVID-19 and worsening hematuria ranged between 5 and 8 d in the reported cases. In the face of a possible second wave of the pandemic, clinicians should be aware that a nontypical course of hematuria or other urinary symptoms might be related to a COVID-19 infection, especially in patients with a pre-existing condition of the urinary tract.

: The authors have nothing to disclose.