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Urodynamically proven lower urinary tract dysfunction in children after COVID‐19: A case series

Abstract Case Since the declaration of COVID‐19 as a pandemic, other unexpected symptoms related to the infection besides the respiratory system have been reported. Although a few case reports have revealed that adult patients with COVID‐19 also complained of urinary frequency and nocturia, the exact pathophysiology is still unclear. In this case series, we present three children aged 14 to 17 years with urodynamically proven lower urinary tract dysfunction (LUTD) following COVID‐19. Outcome None of the patients had constipation or bowel disorder before the diagnosis of COVID‐19. In addition, neurological examination and related imaging revealed no signs of etiological factors. The median time from diagnosis of COVID‐19 infection to the onset of lower urinary tract symptoms was 3 months. Incomplete bladder emptying/urinary retention supported by increased bladder compliance, high post‐micturition residual urine volumes, and absence of detrusor pressure increase during the voiding phase in the pressure flow study (acontractile detrusor in two patients and hypocontractile detrusor in one patient) were observed. Conclusion We observed that LUTD (eg, incomplete bladder emptying, urinary retention) can be prominent some time after the diagnosis of COVID‐19. Even though psychogenic or neurogenic causes may not be excluded completely, clinicians should be aware of a recent COVID‐19 infection in children with sudden‐onset LUTD.


| INTRODUCTION
It has been almost 2 years since the rapid spread of SARS-CoV-2 and the announcement of COVID-19 as a pandemic by the World Health Organization. The respiratory system is the main affected site attacked by this virus. However, numerous reports indicated other system involvement such as neurological and hematopoietic systems in patients diagnosed with COVID-19. 1 On the other hand, there have been growing data on the effects of COVID-19 on the genitourinary system. 2 "COVID-19-associated cystitis" has been defined for adult patients who have had COVID-19 with complaints of urinary frequency and nocturia. 3,4 To our knowledge, lower urinary tract dysfunction (LUTD) associated with COVID-19 in the pediatric population has not been reported in the literature. We present three pediatric cases with urodynamically proven LUTD following COVID-19.

| CASE SERIES
Toilet-trained children under the age of 18 who were admitted to our pediatric urology department with various lower urinary tract symptoms (LUTS) between June 2020 and September 2021 were retrospectively evaluated. Children who were not neurologically intact and T A B L E 1 Demographic and clinical data of patients  been reported that the exaggerated release of pro-inflammatory molecules also known as "cytokine storm" can cause demyelinating diseases in a similar way as in viral diseases. 7 Based on this mechanism, it is also argued that the inflammation and demyelination of the pudendal nerve can cause bladder and bowel incontinence. 8 In contrast, it has been reported that demyelination of the nervous system can also lead to urinary and fecal retention through not completely understood mechanisms. 9 Acute urinary retention, another endpoint of LUTD, is an extremely rare entity in childhood compared to adults. 10  Specific features observed in this disorder are urodynamically increased bladder sensation, hypersensitivity, and the findings of underactive bladder without PMR. 15 Therefore, we think that LUTD observed in our patients differed from bladder somatic symptom disorder or a transient psychogenic disease due to their decreased/normal bladder sensation and increased PMR. However, post-COVID-19 urinary retention still might have a psychogenic cause since our case series include only three patients which limits extrapolation.
Supportive therapy forms the basis of medication in children with COVID-19, so it is a priority to determine the respiratory status, oxygen, and fluid/electrolyte needs. 5 If necessary, it is recommended to start empirical antibiotic therapy for possible community-acquired infections. 5 Glucocorticoids are recommended in cases of persistent fever, severe disease, or development of the multisystemic inflammatory syndrome. 5 Since therapeutic agents (eg, steroids) that could cause neuroinflammation symptoms were not used in any of our patients, the possibility of an etiological factor related to therapeutic agents were excluded.
Since autoimmune antibodies or inflammatory cytokines in urine or blood were not evaluated, we cannot propose a clear hypothesis regarding the molecular pathogenesis. However, we observed that LUTD (eg, incomplete bladder emptying, urinary retention) can be prominent some time after the diagnosis of COVID-19. Based on our findings, clinicians should be aware of a recent COVID-19 infection in children with suddenonset LUTD. Although it is difficult to comment on whether post-COVID-19 urinary retention has psychogenic or neurogenic origins, these factors should also be considered in the differential diagnosis.

CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.

ETHICS STATEMENT
All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

INFORMED CONSENT
Informed written consent was obtained from the patients for publication of this case report without revealing their names and identities.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.