Introduction

In the last days of 2019, a cluster of acute pneumonia from an unknown recourse occurred in Wuhan, Hubei Province, China. The disease has rapidly spread all around the world. World Health Organization (WHO) declared this condition a public health emergency of international concern. The pathogen has been identified as a type of coronavirus, and the disease is described as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1, 2). Most of the patients experience mild symptoms. Fever, fatigue, and cough are the most common symptoms, but there are some rare extra-pulmonary presentations (2-4). Although the respiratory and immune systems are the most commonly affected, there is evidence of other systems’ involvement, such as the nervous and urinary systems (5-8).

Lower Urinary Tract Symptoms (LUTS) describe storage, voiding, and post-voiding problems (9). Voiding problems can be due to various causes, such as underactive bladder and bladder outlet obstruction, that can end in urinary retention (UR). The UR is an inability to wholly or partially empty the bladder and is classified into acute and chronic  (9, 10). There are reports of voiding problems through the course of some viral diseases, such as HIV and HSV infection. Here we presented a report of four cases with newly onset bladder emptying problems and confirmed COVID-19 infection.

Case presentation

Case 1: A 32-year-old man with confirmed COVID disease in April 2021 came to our medical center with a chief complaint of urinary hesitancy. The urinary symptoms started after the COVID-19 infection. During the disease period, he experienced respiratory symptoms and loss of smell, and he received outpatient treatment. 

The ultra-sonographic exam showed the normal condition of both kidneys. The post-voiding residue (PVR) was about 300ml. The bladder wall thickness was within the normal range. The urodynamic study performed in June 2021 revealed an underactive bladder with an interrupted voiding pattern and a Qmax of 3ml/s (Table 1). Bethanechol, tamsulosin, and baclofen were prescribed. Clean intermittent catheterization (CIC) was offered, but he refused. In the last follow-up (October 2021), the ultra-sonographic exam showed a PVR of 150ml. The patient claimed that his urinary functions got better.

Case 2: A 36-year-old man with confirmed COVID disease in June 2021 came to our medical center with a chief complaint of acute urinary retention. In the beginning, the urinary symptoms started concurrently with COVID symptoms. He suffered from severe respiratory symptoms that led to hospitalization. He received antiviral medications (such as remdesivir). The ultra-sonographic exam showed the normal condition of both kidneys. The post-voiding residue was about 400 ml, and the bladder wall thickness was within the normal range. The urodynamic study performed in October 2021 revealed an acontractile bladder with no void (Table 1). Bethanechol, tamsulosin, and baclofen were prescribed, and he underwent CIC. In the last follow-up (1st of November 2021), there were no changes in his urinary symptoms, and he was yet on CIC. 

Case 3: A 27-year-old man with confirmed COVID disease in May 2021 was referred to our medical center from Iraq for Sacral neuromodulation (SNM) implantation. He had an episode of acute urinary retention just after recovery from COVID disease. During the disease, he suffered severe respiratory symptoms that led to hospitalization. 

The ultra-sonographic exam showed the normal condition of both kidneys, a bladder volume of about 450 ml, and an increased bladder wall thickness. The urodynamic study performed in August 2021 revealed an acontractile bladder with no void (Table 1). The CIC has been offered, and he was on medical treatment (bethanechol, tamsulosin, and baclofen).  In the last follow-up (1st of November 2021), he was on CIC and a candidate for SNM.

Case 4: A 38-year-old man with confirmed COVID disease in February 2021 came to our medical center complaining of urinary hesitancy. The urinary symptoms showed up during the COVID infection period. He experienced severe respiratory symptoms that led to hospitalization. He took antiviral medications (remdesivir). 

The ultra-sonographic exam showed the normal condition of both kidneys, a PVR of about 250 ml, and the bladder wall thickness was within the normal range. The urodynamic study performed in April 2021 revealed an underactive bladder with an interrupted voiding pattern and a Qmax of 5ml/s (Table 1). Bethanechol, tamsulosin, and baclofen were prescribed, and he offered to do clean intermittent catheterization (CIC). The patient's symptoms improved in the last follow-up (1st of November 2021), and the ultra-sonographic exam showed a PVR of 150ml. Interestingly, all four cases had no medical history or risk factors predisposing them to voiding problems.

Table 1. [urodynamic results]

Note:  * BCI: bladder contractility index (divided into strong>150, normal: 100–150, and weak<100)

Discussion

In early 2020 a life-threatening respiratory disease called COVID-19 spread worldwide. Today, almost all countries are struggling with different variants of the virus. More than five million deaths have been recorded till now. Although the patients experience fever, fatigue, myalgia, and cough in most cases, a broad spectrum from asymptomatic to severe pulmonary or extra-pulmonary symptoms has been reported (3, 11, 12).

Urinary retention (UR) is a situation of disability of urinating voluntarily. The causes of urinary retention include anatomic obstruction, infections, inflammations, neurological or Pharmacological causes, trauma, etc. The most common cause of UR in men is a benign prostatic obstruction (BPO) (13, 14).

Evidence shows that viral infections can affect lower urinary tract function (15, 16). Studies on the COVID-19 virus showed a specific spike protein characterized by its strong binding affinity to angiotensin-converting enzyme 2 (ACE2) receptors. Then the virus would like to attack the organs which express ACE2, such as the lungs, heart, gastrointestinal tract, and urinary system (16-18). Some reports of myelitis due to COVID-19 infection in patients with acute urinary retention (19-23). Furthermore, some studies showed that urinary symptoms related to BPH are also affected by COVID-19 infection (7, 8). Also, some studies found relations between COVID-19 infection and hyponatremia and LUTS (24, 25).

In this case series, we report four gentlemen who suffered from obstructive LUTS following COVID-19 infection. Two were treated with anti-viral drugs during hospitalization due to respiratory symptoms. All were younger than 40 years old with no history of voiding problems. The ultra-sonographic exam, in all cases, showed normal anatomy of the urinary system.

In the urodynamic study, all had an average cytometric capacity and stable detrusor. Two were unable to void at all. All cases had a significantly high volume of post-void residue.

Detrusor underactivity (DU) is a decreased strength or duration of detrusor contraction needed to empty the bladder (9). effectively. So, all four patients were suffering from detrusor underactivity. We know that theoretically, the bladder can be infected by the COVID-19 virus  (26); however, there is no clear pathogenesis for COVID-19-induced LUTS (27, 28). Since there was no history of any underlying disease or predisposing risk factors relevant to detrusor underactivity, we suggest that decreased detrusor activity contributed to COVID-19 infection. 

Conclusion

It is about a two-and-a-half-year period since the day the COVID-19 outbreak began in China. COVID-19 started as a respiratory disease with flu-like symptoms, but a list of extra-pulmonary symptoms and complications can soon develop. In this study, we presented four recently recovered from COVID-19 infection, which still suffers from voiding problems. However, more studies are warranted regarding the pathogenesis, risk factors, and treatment options of detrusor underactivity as a manifestation of COVID-19 infection. 

Declarations

Author’s contributions

All authors contributed equally.

Acknowledgment

Special thanks to four patients and the Urology and Nephrology Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Conflict of Interest

The authors declare that they have no competing interests.

Funding

No funding.

Ethics Statements

This case series study is based on CARE guidelines and signed written informed consent.

Data Availability

No additional data are available for this editorial

Abbreviations

ACE2                    Angiotensin-converting enzyme 2

BPO                     Benign prostatic obstruction

CIC                       Clean intermittent catheterization

DU                       Detrusor underactivity

LUTS                    Lower urinary tract symptoms

PVR                     Post-voiding residue

SARS-CoV-2        Severe acute respiratory syndrome coronavirus 2

SNM                    Sacral neuromodulation

UR                       Urinary retention

WHO                   World health organization