Association between COVID-19 and increased incidence of overactive bladder symptoms in female patients: A retrospective analysis

Abstract

Introduction and objectives

To investigate female patients' post-COVID-19 voiding symptoms and to research how they relate to overactive bladder (OAB).

Patients

One hundred and forty patients aged 20–50 years who were hospitalised and discharged due to COVID-19 at Kartal Dr. Lütfi Kırdar City Hospital between 2021 and 2022 and 50 patients with a history of COVID-19 among two hundred female patients who presented to the urology outpatient clinic with symptoms related to OAB were retrospectively analysed. Bladder diary, overactive bladder symptom score (OABSS), uroflowmetry values and time of onset of symptoms of symptomatic patients were recorded for all patients. Disease-free individuals for control purposes were not included in the study.

Results

It was observed that 38% of 140 hospitalized patients had a symptomatic change related to OAB, and there was a significant difference in voiding diary, OABSS, and uroflowmetry Qmax values between symptomatic and non-symptomatic patients after COVID-19. (p:0.001) There was a significant difference between the pre-COVID-19 (estimated) and post-COVID-19 (current) voiding diary and OABSS values of all symptomatic patients (with and without a history of hospitalization). (p:0.001) When these two groups were compared with each other, there was a significant difference between the post-COVID-19 voiding diary, OABSS values, and the meantime to the onset of symptoms in inpatients and outpatients (p:0.001)

Conclusion

COVID-19 may be associated with urgency/urge incontinence and overactive bladder in female patients.

Resumen

Introducción y objetivos

Investigar los síntomas miccionales posteriores a COVID-19 de las pacientes femeninas y su asociación con la vejiga hiperactiva (VH).

Pacientes

Se analizaron retrospectivamente 140 pacientes de entre 20 y 50 años que fueron hospitalizadas COVID-19 y dadas de alta por en el Hospital Kartal Dr. Lutfi Kirdar entre 2021–2022, y 50 pacientes con antecedentes de COVID-19 entre doscientas pacientes femeninas que se presentaron en la consulta externa de urología con síntomas relacionados con la VH. Para todas las pacientes se registró el diario vesical, la escala de puntuación de síntomas de vejiga hiperactiva (OABSS por sus siglas en inglés), los valores de uroflujometría y el tiempo hasta la aparición de los síntomas de las pacientes sintomáticas. No se incluyeron en el estudio individuos libres de la enfermedad a efectos de control.

Resultados

Se observó que el 38% de las 140 pacientes hospitalizadas presentaba nuevos síntomas relacionados con la VH, y hubo una diferencia significativa en los valores del diario miccional, la OABSS y los valores de flujo máximo (Qmax) de la uroflujometría entre las pacientes sintomáticas y las no sintomáticas después del COVID-19. (p: 0.001) Hubo una diferencia significativa entre los valores del diario vesical y OABSS anteriores al COVID-19 (estimados) y posteriores al COVID-19 (actual) de todas las pacientes sintomáticas (con y sin hospitalización previa) (p: 0.001). Al comparar entre grupos, hubo una diferencia significativa entre el diario vesical post-COVID-19, los valores de la OABSS y el tiempo transcurrido hasta la aparición de los síntomas en las pacientes hospitalizadas y ambulatorias (p: 0.001).

Conclusiones

El COVID-19 puede estar asociado con urgencia/incontinencia urinaria de urgencia y vejiga hiperactiva en pacientes femeninas.

Introduction

According to the International Continence Society (ICS), overactive bladder syndrome (OAB) as “urinary urgency, usually accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI) in the absence of urinary tract infection (UTI) or other diseases”.¹ To diagnose OAB, it is advised that at least a 3-day voiding diary be completed. It has been reported that urodynamics does not affect treatment outcomes in patients with OAB unless there is an accompanying neurogenic pattern.² Particularly advised for treatment is pelvic floor muscle training (PFMT), anticholinergic drugs and transcutaneous tibial nerve electrical stimulation (TTNS) can also be preferred.³

COVID-19 (coronavirus disease 2019) is a viral disease that has spread rapidly since 2019. The causative type is the betacoronavirus genus SARS-CoV2, which includes SARS-CoV and MERS-CoV.⁴ Typical symptoms; myalgia, diarrhea and loss of taste and smell, and it has been shown to be mortal in case of comorbidity.⁵ Urologically, COVID-19 is more associated with testicular and renal dysfunction and is unlikely to be detected in urinalysis.^6–8 There have been some studies on the connection between COVID-19 and the urinary system, but it is still unclear from the literature exactly how this disease affects the urinary system.^9–11

We observed that during this pandemic period, the urinary symptoms of female patients presenting to our outpatient clinic with COVID-19 also increased. Based on this concept, we attempted to collect data by retrospectively reviewing both female patients who presented to our outpatient clinic with OAB after COVID-19 and female patients who were hospitalized and discharged from our hospital due to COVID-19.

Materials and methods

Ethical considerations and study population

Following approval from the ethics committee, 187 female patients between the ages of 20 and 50 who received inpatient treatment for COVID-19 at Kartal Dr. Lütfi Kirdar City Hospital between 2021 and 2022, as well as 200 female patients between the ages of 22 and 60 who applied to the urology polyclinic with OAB symptoms were retrospectively screened.

Exclusion criteria and data collection

Twenty patients with a history of hospitalization were excluded because of cardiovascular and neurological conditions, 18 because they were taking drugs for OAB, six because they had previously undergone ureteral stone surgery, and three because they had a history of bladder cancer. Of the 200 outpatients, sixty had a history of COVID-19. Six of these 60 patients were excluded from the study because they had a history of hospitalization due to COVID-19, two because they had a history of bladder tumor, and the other two because the COVID-19 procedure left neurological sequelae in their lower extremities. One hundred ninety patients in total were thus included in the study (Fig. 1). After COVID-19, patients were split into two groups: those who had and did not have lower urinary tract symptoms, and at this point, the overactive bladder symptom score (OABSS) was used. All patients completed a bladder diary (number of daily urinations) OABSS form before (estimated) and after (current, at least three days) COVID-19, and a complete urinalysis and uroflowmetry were performed. Symptomatic patients were questioned about the time to onset of symptoms after COVID-19.

Figure 1.

Categorization of patients.

Statistical analysis

All statistical analyses were performed using SPSS 22.0 (IBM® SPSS® Statistics V22.0, 2013, USA). The patients' bladder diary and OABSS were compared before and after COVID-19. Symptomatic patients were also investigated according to the predominant symptom type. Independent Samples t-test, Paired sample t-test, and Pearson Chi-Square test and Mann-Whitney U test were used for statistical analysis and P < .05 was considered statistically significant.

Results

Of 140 patients hospitalized due to COVID-19, 38% (n:54) have had symptomatic changes compatible with OAB. While there was no statistically significant difference between symptomatic and non-symptomatic patients in this group in terms of estimated bladder diary, OABSS, and length of hospital stay before COVID-19, a significant result was observed between the two groups after COVID-19 (p:0.001) (Table 1). In addition, there was a significant statistical difference between bladder diary and OABSS values before and after COVID-19 in both patients hospitalized due to COVID-19 and symptomatic patients admitted to the urology outpatient clinic. (p:0.001) (Table 2).

Table 1.

Comparison of all female patients hospitalized due to COVID-19 and did not have a previous urological application.

	Overall (n:140) mean ± SD	Symptomatic (n:54) mean ± SD	Non-Symptomatic (n:86) mean ± SD	p
Age	26.6 ± 4.3	26.7 ± 4.1	26.5 ± 4.5	0.892*
Bladder Diary 1	6.06 ± 1.1	5.98 ± 1.01	6.12 ± 1.15	0.483*
Bladder Diary 2	8.31 ± 3.57	12.59 ± 1.63	5.63 ± 0.57	0.001*
Hospitalization Day	3.85 ± 2.52	3.87 ± 2.71	3.83 ± 2.41	0.940*
OABSS 1	3.01 ± 2.2	3.06 ± 2.19	2.98 ± 2.22	0.838*
OABSS 2	8.31 ± 3.57	19.78 ± 6.98	3.09 ± 2.4	0.001*
Uroflowmetry Qmax	23.2 ± 6.28	26 ± 5.76	21.5 ± 5.98	0.001*
Uroflowmetry Qaverage	15.4 ± 3.08	15.26 ± 3.32	15.58 ± 2.94	0.556*
Voided volume(cc)	284.9 ± 100.7	290.3 ± 101.1	281.1 ± 100.8	0.579*
Post-void residual urine volume(cc)	12.3 ± 1.62	14.96 ± 21.47	10.67 ± 17.4	0.296***
Distribution of patients by uroflowmetry type
Smooth continuous(n:89)	19	70		0.001**
Tower(n:41)	29	12
Fluctuating(n:6)	2	4
Interrupted(n:3)	3	0
Supervoider(n:1)	1	0

OABSS 1/2: The estimated overactive bladder symptom score before/after hospitalization. Bladder Diary 1: Pre-COVID (estimated), Bladder Diary 2: Post-COVID (at least 3 days).

*

Independent Samples t test.

**

Pearson Chi-Square.

***

Mann-Whitney U test.

Table 2.

Observational analysis results of symptomatic patients hospitalized with COVID-19 and outpatients admitted after COVID-19 compared to before.

		p
Hospitalizated
Bladder Diary 1	5.98 ± 1.01	<0.001*
Bladder Diary 2	12.59 ± 1.63
OABSS 1	3.06 ± 2.19	<0.001*
OABSS 2	19.78 ± 6.98
Non-Hospitalizated
Bladder Diary 1	5.96 ± 1.09	<0.001*
Bladder Diary 2	8.74 ± 2.47
OABSS 1	2.2 ± 1.8	<0.001*
OABSS 2	11.4 ± 3.9

OABSS 1/2: The estimated overactive bladder symptom score before/after hospitalization. Bladder Diary 1: Pre-COVID (estimated), Bladder Diary 2: Post-COVID (at least 3 days).

*

Paired sample t test.

When hospitalized and non-hospitalized patients were compared with each other, there was a significant difference in bladder diary, OABSS values, and the meantime until the onset of symptoms after COVID-19 (p:0.001) (Table 3).

Table 3.

Comparison of symptomatic patients according to hospitalization status and dominant symptom type.

	Overall (n:104) mean ± SD	Hospitalizated (n:54)	Non-Hospitalizated (n:50)	p
Age	33.4 ± 10.6	26.6 ± 4.1	40.6 ± 10.8	0.001*
Bladder Diary 1	5.97 ± 1.00	5.98 ± 1.01	5.96 ± 1,00	0.982*
Bladder Diary 2	10.7 ± 2.83	12.59 ± 1.63	8.74 ± 2.47	0.002*
OABSS 1	2.64 ± 2.06	3.06 ± 2.19	2.20 ± 1.82	0.282*
OABSS 2	15.7 ± 7.0	19.78 ± 6.98	11.40 ± 3.9	0.001*
Symptom onset time (months)	4.46 ± 1.55	3.61 ± 1.1	5.38 ± 1.39	0.001*
	Symptom Type			0.506**
	Dysuria	20	18
	Urgency and Urge incontinence	25	20
	Polyuria	4	8
	Nocturia	5	4
	Uroflowmetry parameters
	Qmax	26,0 ± 5.7	18.8 ± 3.3	0.001*
	Qaverage	15.1 ± 3.38	13.5±2.49	0.006*
	Voided volume (cc)	290.3 ± 101.1	285.8 ± 97.1	0.793*
	Post-void residual urine volume (cc)	14.96 ± 21.47	12.8 ± 19.9	0.610*
	Uroflowmetry type			0.330**
	Smooth continuous	19	23
	Tower	29	18
	Fluctuating	2	2
	Interrupted	3	3
	Supervoider	1	4

OABSS 1/2: The estimated overactive bladder symptom score before/after hospitalization. Bladder Diary 1: Pre-COVID (estimated), Bladder Diary 2: Post-COVID (at least 3 days).

*

Independent Samples t test.

**

Pearson Chi-Square.

Urinary urgency and urge incontinence were the most frequently reported complaints among all symptomatic patients. In hospitalized patients, the maximum flow rate and average flow rate were 26.0 and 15.1, respectively, with statistically significant differences observed (p: 0.001, 0.006). However, no significant differences were found between the two groups in terms of uroflowmetry pattern types or symptom types (Table 3). Among symptomatic patients with either a history of hospitalization or as outpatients, urinary urgency and urge incontinence were the most commonly reported complaints. The uroflow parameters indicate that the maximum flow rate (q max) and mean flow rate (mean q) of inpatients were 26.0 and 15.1, respectively, with a statistically significant difference between them (P < .001, .006). Nonetheless, there were no significant differences noted between the two groups regarding the uroflowmetry pattern types or symptom types (refer to Table 3).

Discussion

The potential of COVID-19 to cause numerous pathologies in addition to its established symptoms and its impact on the urinary system has recently come to the fore. Our study was designed by the observation of a rise in female patients experiencing lower urinary tract symptoms after contracting COVID-19 in our outpatient clinic. Based on a literature review, Lamb et al. COVID-19-associated cystitis (CAC) was identified, with the claim that the presence of inflammatory cytokines in the urine increased.¹¹ Yet again, Bernikov et al.'s study from 2021 noted that “COVID-19 has a role in the development of lower urinary tract symptoms (LUTS), but its mechanism is not clear”.¹² In a recent article, it was noted that COVID-19 and social distancing measures have had a negative impact on the symptoms of Overactive Bladder (OAB) and quality of life in women undergoing different treatments.¹³ Research on the psychiatric effects of COVID-19 supports this hypothesis.^14,15 It is believed that quarantine measures and anxiety over exposure to the virus are the primary factors contributing to symptoms in these patients.

In a different current article, Mumm et al. suggested that lower urinary tract symptoms of COVID-19 increase in male patients, and this process is associated with viral cystitis.¹⁶ Furthermore, current studies in the literature support that COVID-19 causes an increase in benign prostatic hyperplasia (BPH) related to lower urinary tract symptoms.^17,18 In a recent study by Esteban-Fuertes Metal, it was shown that BPH causes OAB-related symptoms in a significant portion of men presenting with LUTS.¹⁹ In this regard, we restricted our analysis to female patients due to the ambiguity surrounding the potential aggravation of BPH and related symptoms post-COVID-19 and whether the change in symptoms is localized to the bladder.

Studies have suggested a correlation between COVID-19 and bladder function, with increased occurrences of haematuria potentially leading to more pronounced symptoms of urgency, urge incontinence, and nocturia in patients, and a potential association with bladder dysfunction.²⁰ Similarly, Kaya et al. reported that lower urinary tract symptoms (LUTS) (especially irritative symptoms) may be early indicators of COVID-19.²¹ However, our study focuses on post-COVID changes. This decision was made due to the increased number of female patients seeking treatment at our polyclinic after contracting COVID-19, as previously mentioned.

Based on both literature and obtained data, the critical effect of COVID-19 on the bladder appears to be detrusor overactivity. However, relying solely on anamnesis, urinalysis, uroflowmetry, questionnaires, and bladder diary may not supply adequate information for diagnosing and managing this disease. From this perspective, we acknowledge that the study is flawed by the lack of cystoscopic and cytological findings in the patients we followed and by the omission of urodynamic testing. We think that it is worth noting that the impact of COVID-19 on the urinary system is not yet fully known, leaving us in a dilemma as to whether further research is necessary to approach these patients. Furthermore, we want to indicate that these patients' follow-up is ongoing, and some of them have begun bladder antimuscarinic treatment. As these patients' drug treatment and follow-up procedures continue, we see the study's inability to provide precise data as another shortcoming.

The main limitations of our study include its retrospective design, the dearth of information in the pre-COVID-19 bladder diary and the OABSS forms, and, as already mentioned, the lack of data on drug therapy and its administration. We should also mention that we are experiencing difference of opinion, particularly in the days leading up to COVID-19, and that OABSS and voiding diaries were unable to achieve. However, we believed this could be accomplished by providing our patients with complete information. We had assumed that no inquiry form could be completed before Covid-19; however by relying on Turkish validation of the symptom inquiry forms and providing the relevant patient-related details, we believe that the literature will benefit from this data.^22,23 We also state that the inquiry forms completed prior to COVID-19 could not be completed for at least three days, which is another shortcoming.

We know that since the spread of COVID-19 in our country and around the world, the number of relapses has increased, and many people have had COVID-19 multiple times. As a result of this, we see a lack of information about how frequently our patients have had COVID-19 as another point of criticism. However, we would like to emphasize that we are currently collecting data and conducting a long-term study that involves multiple centers. Another criticism of our study is the uncertainty surrounding symptomatic changes in patients with pre-existing overactive bladder symptoms post-COVID-19. However, we excluded these patients from the study to obtain specific data on the symptomatic changes in non-symptomatic patients after COVID-19.

The absence of conclusive information regarding the psychogenic effects of COVID-19 and its connection to overactive bladder is another point of criticism. Given that hospitalized patients experience this process at a more demanding pace, we would like to draw attention to the possibility that OAB may be connected to the psychogenic effect of this process, and a study could be planned.

Conclusion

We are opinion that COVID-19 has an effect on the bladder that is not yet clear and that this effect is associated with urgency and urge incontinence, especially in female patients. However, different results may be obtainable according to multicentric long-term studies and medical treatment response status.

Ethical/Institutional Review Board Approval

Istanbul Kartal Dr. Approval was obtained from the ethics committee of Lütfi Kırdar City Hospital at 29.11.2022. (IRB number: 2022/ 51 41238/6).

Funding

The authors declared that this study has received no financial support.

Conflict of interest

No conflict of interest was declared by the authors.

Acknowledgments

Thanks to Assoc. Prof. Dr. Fatih TARHAN and urogynecology nurses.