Longitudinal Evaluation of Lower Urinary Tract Symptoms up to Six Months after COVID-19 Infection in a Jordanian Cohort

Abstract

Background:

Lower Urinary Tract Symptoms (LUTS) refer to a range of urinary symptoms affecting both men and women. These symptoms include increased frequency of urination, urgency, weak urine flow, incomplete emptying of the bladder, and nocturia.

Objective:

LUTS encompass various urinary issues, with emerging evidence suggesting a potential connection to COVID-19. This study aimed to evaluate the occurrence and long-term effects of COVID-19 on LUTS and IPSS across different infection severities.

Methods:

The prospective observational study enrolled 85 COVID-19 patients. IPSS was used to assess LUTS before, during, and 3 and 6 months after infection. Data collection included demographics and clinical characteristics, with follow-up assessments of all participants, highlighting significant differences between severity groups through statistical analysis.

Results:

The highest IPSS values occurred during the acute phase of infection in all groups. Patients with severe or critical COVID-19 exhibited the highest IPSS, while asymptomatic or mild cases had the lowest scores. IPSS scores showed a significant association across all phases in patients with a history of urological disorders compared to those without. Age was positively correlated with IPSS before and during infection. Long-term bladder dysfunction associated with COVID-19 may cause persistent LUTS in patients with mild cases.

Conclusion:

A significant association exists between COVID-19 and LUTS, indicating that LUTS should be considered in COVID-19 cases. Monitoring LUTS is recommended throughout COVID-19 and during recovery. However, pre-infection LUTS were assessed retrospectively through recall of IPSS scores, which may be subject to recall bias and could affect the accuracy of pre- and post-infection comparisons. This study is among the first to provide a 6-month longitudinal follow-up with predictors such as age and urological history. Limitations include the lack of control for confounding factors and potential recall bias, though the within-subject repeated design enhances the strength of the results.

1. BACKGROUND

Lower Urinary Tract Symptoms (LUTS) refer to a range of urinary symptoms affecting both men and women. These symptoms include increased frequency of urination, urgency, weak urine flow, incomplete emptying of the bladder, and nocturia. While LUTS can be caused by various factors, including aging and certain medical conditions, it has been observed that COVID-19 infection can also contribute to the development or exacerbation of these symptoms. COVID-19, caused by the novel coronavirus SARS-CoV-2, primarily affects the respiratory system (1). However, the virus can also impact other organs and systems in the body, including the urinary system (2, 3). Several studies have reported that COVID-19 patients may experience urinary symptoms, particularly LUTS, during the infection (4).

The exact mechanisms underlying the development of LUTS in COVID-19 infection are not fully understood. However, several hypotheses have been proposed. One possibility is that the virus directly infects the urinary system, leading to inflammation, dysfunction, and manifestation of symptoms of urinary tract infection (5). The presence of viral particles and genetic material has been detected in urine samples of some COVID-19 patients, supporting this hypothesis (6). The inflammatory response triggered by the infection could affect the smooth muscle and nerve function in the lower urinary tract, resulting in LUTS.

The SARS-CoV-2 virus enters host cells by binding to the angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) receptors (7). Tissue expression levels of ACE2 and TMPRSS2 indicate the participation of various organs and the resulting range of clinical symptoms (8). Furthermore, infection with SARS-CoV-2 may result in a hyperactivated renin-angiotensin system (RAS), leading to the activation of pro-inflammatory pathways and increased release of cytokines. Consequently, the virus may exacerbate LUTS, trigger inflammatory responses in the prostate gland, and worsen benign prostatic hyperplasia (BPH) and its associated symptoms through ACE2 signaling pathways. Since androgen receptors play a crucial role in the pathophysiology of BPH, and androgen pathways may mediate COVID-19 infection, the virus could accelerate BPH progression and exacerbate its associated symptoms through androgen receptor involvement and related metabolic disturbances (4). Moreover, one study reports that approximately 2.4% of bladder cells express ACE2, suggesting that, like the respiratory system, the urinary bladder may also be vulnerable to COVID-19 infection (9).

Individuals with COVID-19, even if they are asymptomatic, are more prone to experiencing LUTS compared to those who have not been infected by the SARS-CoV-2 virus (10). One study proposes that LUTS, particularly storage symptoms, could manifest as one of the initial indicators of COVID-19 (11). Additionally, the severity of COVID-19 appears to be linked to the IPSS score reflecting lower urinary tract symptoms (12). Therefore, healthcare professionals should assess LUTS alongside other recognized symptoms of the virus when suspecting a patient of having COVID-19.

One approach to assessing the prostatic status in susceptible patients is through the use of questionnaires like the International Prostate Symptom Score (IPSS) (13) which is an international version of the American Urological Association-symptom index. The IPSS is a widely used tool that evaluates the severity of lower urinary tract symptoms associated with BPH. Even though originally it was validated in men with BPH, IPSS is also applicable for women and can be used to evaluate female lower urinary tract dysfunction (14). It consists of seven questions related to urinary symptoms and an additional question regarding the patient’s quality of life. By administering the IPSS, healthcare professionals can quantify the degree of symptom severity and monitor changes over time. Since the relationship between COVID-19 and BPH is still not well-established, more research is needed to understand any potential connections. The use of questionnaires like IPSS can aid in assessing the prostatic status in susceptible patients and may help identify patterns or associations. Moreover, our study is the first to track symptom progression over time by analyzing IPSS scores at both three and six months post-infection, providing new insights into the trajectory of LUTS in COVID-19 survivors. Our study, compared with previous cross-sectional studies, followed LUTS trajectories of six months, therefore, our study offers longitudinal data on persistence and risk determinants in a Middle Eastern population, which is under-represented in the existing literature.

2. OBJECTIVE

This prospective study aimed to assess the prevalence and severity of LUTS among patients admitted to the hospital with COVID-19 infection. This study would help to gain insights into the occurrence of LUTS among individuals affected by COVID-19. By doing so, it will facilitate the development of effective approaches for managing these symptoms.

3. MATERIAL AND METHODS

Study Design and Setting

This prospective observational study was conducted at Gardens Hospital in Amman, Jordan, and its reporting follows the STROBE guidelines (15). The study included patients admitted with SARS-CoV-2 infection between June 13 and December 13, 2021. The study aimed to investigate the impact of COVID-19 infection on lower urinary tract symptoms (LUTS) over a six-month follow-up period using the International Prostate Symptom Scoring.

Inclusion and Exclusion Criteria

Patients over 18 years of age, of both genders, who were either hospitalized or diagnosed with COVID-19 via PCR testing of nasopharyngeal or oropharyngeal swabs, in accordance with World Health Organization (2021) guidelines (16) were included in the study. The severity of COVID-19 infection was classified according to the World Health Organization’s clinical criteria (17) which categorize cases as mild, moderate, severe, or critical based on respiratory status, oxygen requirements, and overall clinical condition. Asymptomatic/presymptomatic cases refer to individuals who test positive for SARS-CoV-2 without showing any symptoms. Mild illness includes individuals with symptoms such as fever and cough, but with normal respiratory function and chest imaging. Moderate illness is characterized by evidence of lower respiratory disease with oxygen saturation ≥94% on room air. Severe illness involves breathing issues and lung hyperinflation. Critical illness includes patients with respiratory failure, life-threatening blood infections, and major systemic organ breakdown. Critical patients with catheters were excluded from the study because the presence of a catheter can significantly alter the natural presentation of lower urinary tract symptoms, leading to inaccurate or non-representative IPSS scores. Moreover, patients with urinary tract operations or urological cancers were also excluded. To ensure comprehensive evaluation, all patients underwent a bacteriological examination of the urine to identify any associated urinary infections. The study initially included 100 patients after the initial screening. however (15) patients did not meet the inclusion criteria and were dropped out. Thus, 85 participants were included in the final sample. No participants were lost to follow-up at the 6-month interval. All enrolled participants were successfully monitored and assessed for their IPSS scores at all-time points.

Study Tool

The “International Prostate Symptom Score (IPSS)” is a widely utilized tool for assessing the severity of lower urinary tract symptoms associated with BPH in Men. However, Okamura et al. (18) studied the validity of the International Prostate Symptom Score (IPSS) for assessing lower urinary tract symptoms (LUTS) in female patients. Although it was initially developed for men, IPSS shows strong psychometric measurement qualities in women, demonstrating good reliability and validity comparable to men. Even though some variations still exist in how different groups experience symptoms, the overall findings support that the IPSS is a relevant and useful tool for evaluating LUTS in both women and men. IPSS is used to measure lower urinary tract symptoms (LUTS) in both men and women with COVID-19 in the current Jordanian study. The IPSS is reliable for women, as shown by Okamura et al., ( 18) who found strong consistency (Cronbach’s α = 0.79–0.81) and validity in 746 women. Hsiao et al. (14) confirmed it can identify voiding issues in 222 women (IPSS-V/S ≥ 1.33, 92.9% sensitivity) and storage symptoms, correlating with other tests (ρ = 0.74). Boyle et al. (19) showed similar LUTS rates in 4979 men and 3790 women across four countries (e.g., 25.1% vs. 23.7% in Birmingham), and Ponholzer et al. (20) found comparable results (27% men, 31% women). The IPSS measures symptoms like frequency and nocturia, common in our study (nocturia 75% before, 93% during infection), which apply to both genders. The Arabic version is suitable for our patients in Jordan. The IPSS’s widespread use allows comparisons with other studies, and Hsiao et al. ( 14) supports our sample’s reliability (power = 0.9997). This suggests that the IPSS can be confidently employed in research and clinical practice to assess and monitor LUTS in female patients. The IPSS consists of eight questions: seven questions about urinary symptoms (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia). Each symptom question is scored from 0 to 5, with the total score ranging from 0 to 35. The scores are interpreted as follows:

• 0-7: Mild symptoms.

• 8-19: Moderate symptoms.

• 20-35: Severe symptoms.

The IPSS questionnaire is valuable for evaluating the LUTS status of susceptible patients through the total LUTS score, potentially uncovering patterns or associations.

Data Collection

Following the selection of study participants based on inclusion and exclusion criteria, patients were explained in detail about the study objective and provided a questionnaire by an independent researcher. Upon agreement of patients to participate in the study, medical history and socio-demographic details were obtained. Patient data and clinical information collected included the following: age, sex, diagnosis of COVID-19 through PCR testing and clinical assessment according to Stanford Medicine’s Diagnosis and Treatment Plan of COVID-19, and LUTS (presence and severity) before and during the clinical manifestation of COVID-19 infection and at 3 and 6 months after the initial infection. Baseline data was collected retrospectively as the patients were included in the study when they were hospitalized or tested positive for COVID-19. Patients provide data about their urinary symptoms to researchers by recalling their condition before getting affected by COVID-19. In clinical research, retrospective recall is a commonly used technique, especially when prospective collection of baseline data is not feasible. Patients can reasonably recall their pre-infection symptoms because of the structured framework of the IPSS questionnaire. To ensure reliability, patients were provided with a detailed explanation of each symptom during data collection, and the recall period was kept short preceding their illness, minimizing the impact of recall bias. Since COVID-19 was an emergent disease, the study team could not take samples from people before they became infected. The researchers had to rely on patients’ memory to gather pre-infection information. Hence the retrospective recall remains the only practical approach for obtaining pre-infection baseline data. The severity levels were categorized into asymptomatic, mild, moderate, severe, and critical. Participants filled out the questionnaire at multiple time points: before hospitalization for COVID-19, during infection, and post-hospitalization. The IPSS scores were measured at these different time points to track changes in symptom severity: before infection, during infection, 3 months after infection, and 6 months after infection.

Statistical analysis

Recorded data were compiled and entered into a spreadsheet (Microsoft Excel 2010) and then exported to the data editor page of IBM SPSS version 22.0 (SPSS Inc., Chicago, Illinois, USA). Descriptive and inferential statistics were used. Mean and standard deviations were computed for numerical variables, and frequency and percentages were used to examine categorical variables. Repeated measures ANOVA and one-way ANOVA were used to compare the means of paired and unpaired variables, respectively. The confidence interval and p-value were set for all tests at 95% and ≤ 0.05, respectively.

Ethical consideration

This study was approved on May 15, 2021, by the Institutional Review Board (IRB) of the Faculty of Medicine, Mutah University, Karak, Jordan (Approval Number: 15052021). The study was strictly conducted in accordance with the guidelines of the Declaration of Helsinki, 7th revision (2013).

4. RESULTS

Patient demographic and clinical details of study participants

The study employed a prospective design and included 85 patients, of whom 44 (51.8%) were male and 41 (48.2%) were female. The mean age was 50.65 ± 18.48 years for males and 48.6 ± 12.49 years for females. The majority of participants were married (60; 70.6%), while 13 (15.3%) were single, 11 (12.9%) were widowed, and 1 (1.2%) was divorced. The study also assessed the frequency and severity levels of COVID-19 infection among participants. A high proportion, 81 (95.3%), tested positive for COVID-19 via PCR. Of these, 31 (36.4%) were classified as severely infected. 4 (4.7%) patients were asymptomatic, while 24 (28.2%) and 23 (27%) showed mild and moderate symptoms, respectively. A small number of patients (3; 3.5%) were critically ill, based on the classification criteria from Stanford Medicine’s Diagnosis and Treatment Plan for COVID-19 (Table 1).

Table 1. Demographic details and clinical status of the patients.

Variables	n (%)
Gender
Male	44 (51.7)
Female	41 (48.2)
Marital status
Single	13(15.3)
Married	60 (70.6)
Widowed	11 (12.9)
Divorced	1 (1.1)
Clinical status
Asymptomatic	4 (4.7)
Mild	24 (28.2)
Moderate	23 (27)
Severe	31 (36.4)
Critical	3 (3.5)

3.2. Comparative assessment of IPSS at different times of infection

The mean of the International Prostate Symptom Score (IPSS) revealed significant association across different time points (before, during, and at 3 and 6 months after infection) as illustrated in Table 2. This indicates that COVID-19 infection may have a prolonged impact on LUTS, with symptoms worsening even six months after the initial infection. For further clarity on where significant differences occurred between time points, a Post Hoc analysis was conducted.

Table 2. Post Hoc Test. * indicates a statistically significant difference at ≤0.05 as calculated by repeated measures ANOVA with the post hoc test. SD: standard deviation.

Assessment Timepoint	International Prostate Symptom Score (Mean + SD)	p-value
Before infection	5.41 + 5.57	0.000*
During infection	9.65 + 7.26
3 months after infection	7.51 + 6.61
6 months after infection	8.92 + 6.11

Table 3 shows that the mean IPSS differed significantly between the pre-COVID-19 period and during COVID-19 infection, indicating a worsening of LUTS during infection. Pairwise comparisons revealed a significant difference in mean IPSS before and during the infection. However, the differences between the ‘during infection’ period vs both three months post-infection and six months post-infection were not statistically significant. This suggests that most recovery likely occurred within the first three months following infection, with no substantial improvement observed by six months.

Table 3. Post Hoc Test.

Group	Mean difference	p-value
Before–During	-4.23	0.000*
Before–3 months after	-2.09	0.086
Before–6 months after	-3.51	0.000*
During–3 months after	2.14	0.126
During–6 months after	0.72	1.00
3 months after–During–6 months after	-1.41	0.672

Comparative assessment of IPSS in patients with different levels of COVID-19 severity

The comparative assessment of IPSS in patients with different levels of COVID-19 severity demonstrated a significant impact on LUTS (Table 4). Severity levels included asymptomatic, mild, moderate, severe, and critical. During infection, patients with severe COVID-19 reported the highest IPSS (13.19 ± 8.11), followed by those with critical illness (10.33 ± 7.51). In contrast, asymptomatic and mild cases had lower scores (3.00 ± 3.61 and 5.54 ± 5.63, respectively). These differences were statistically significant during infection (p = 0.001) for severely and critically infected patients.

Table 4. Comparative assessment of the mean International Prostate Symptom Score according to the severity of COVID-19 infection. Notes: One-way ANOVA with the post hoc test. *indicates a statistically significant difference at (p≤0.05). SD= Standard Deviation.

Severity of COVID-19 infection	IPSS (Before) (Mean ± SD)	IPSS (During) (Mean ± SD)	IPSS (After 3 months) (Mean ± SD)	IPSS (After 6 months) (Mean ± SD)
Asymptomatic	3.33 ± 4.93	3.00 ± 3.61	4.33 ± 2.51	6.33 ± 2.51
Mild	2.54 ± 3.06	5.54 ± 5.63	7.54 ± 6.19	7.75 ± 5.19
Moderate	6.26 ± 4.45	9.78 ± 5.14	5.96 ± 5.97	8.87 ± 7.65
Severe	6.88 ± 6.89	13.19 ± 8.11	7.88 ± 6.91	10.16 ± 5.56
Critical	8.33 ± 7.63	10.33 ± 7.51	18.33 ± 5.85	8.00 ± 8.54
p-value	0.031*	0.001*	0.035*	0.601

At three months post-infection, critical cases showed the highest IPSS (18.33 ± 5.85), followed by severe cases (7.88 ± 6.91), while mild and asymptomatic cases continued to show lower scores. The differences remained statistically significant (p = 0.035), suggesting that the impact of severe and critical COVID-19 on LUTS persisted beyond the acute phase.

By six months post-infection, however, differences in IPSS across severity groups were no longer statistically significant (p = 0.601). This indicates that most patients experienced some degree of improvement in LUTS. Nevertheless, the symptoms did not fully resolve in all groups.

To identify which levels of COVID-19 severity significantly influenced IPSS, post hoc tests were conducted (Table 5). During the infection phase, a significant difference was observed between the mild and severe groups (p = 0.001). Moreover, at 3 months post-infection, a significant difference was found between the moderate and critical groups (p = 0.021). These findings highlight the role of COVID-19 severity in making LUTS worse during the acute phase of the illness.

Table 5. Post Hoc Test.

Groups	Before		During		3 months
	Mean difference	p-value	Mean difference	p-value	Mean difference	p-value
Asymptomatic-Mild	0.792	1.00	-2.54	1.00	-3.21	1.00
Asymptomatic-Moderate	-2.928	1.00	-6.78	0.98	-1.62	1.00
Asymptomatic-Severe	-3.54	1.00	-10.18	0.12	-3.54	1.00
Asymptomatic-Critical	-5.00	1.00	-7.33	1.00	-14.00	0.085
Mild-Moderate	-3.71	0.197	-4.24	0.307	1.58	1.00
Mild-Severe	-4.33	0.036*	-7.64	0.001*	-0.33	1.00
Mild-Critical	-5.79	0.811	-4.79	1.00	-10.79	0.069
Moderate-Severe	-0.61	1.00	-3.41	0.631	-1.91	1.00
Moderate-Critical	-2.07	1.00	-0.55	1.00	-12.37	0.021*
Severe-Critical	-1.45	1.00	-2.85	1.00	-10.45	0.079

Prevalence of urological symptoms among the study population

Figure 1 illustrates the prevalence of lower urinary tract symptoms (LUTS) among the study population at four different time points: before, during, three months after, and six months after COVID-19 infection. Before infection, the most commonly reported symptoms were nocturia (75%), frequency (55%), and urgency (51%), while other symptoms such as incomplete emptying, intermittency, straining, and weak stream were reported less frequently.

Figure 1. Prevalence of urological symptoms among the study population before, during, and after COVID-19.

During COVID-19, there was a substantial increase in all LUTS. Nocturia showed an increase from 75% before infection to 93% during infection. Urgency and frequency also increased, reaching 69% and 79%, respectively. Three months post-infection, the prevalence of some symptoms decreased from the peak observed during infection but remained higher than pre-COVID levels. For example, nocturia dropped to 64%. However, urgency increased from 69% to 71%, and frequency remained the same.

At six months post-infection, some improvement was observed, but several symptoms persisted at elevated levels. These include nocturia (82%), frequency (86%), and urgency (59%), suggesting that for many patients, LUTS may persist long after recovery from COVID-19.

Comparative assessment of IPSS and previous urological symptoms

The comparative assessment of IPSS in relation to prior urological symptoms was evaluated for different time points in the study, as shown in Table 6. Age was included as a covariate in the analysis. Results showed that patients with a history of urological symptoms consistently had higher IPSS scores than those without such a history. During infection, the mean IPSS was 10.98 ± 7.66 in patients with previous urological conditions, compared to 7.23 ± 6.01 in those without. This difference remained substantial at three months post-infection (8.43 ± 6.80 vs. 5.50 ± 5.69) and six months post-infection (9.59 ± 6.38 vs. 7.40 ± 5.23). The difference between both categories reached statistical significance (p = 0.026).

Table 6. Comparative assessment of the mean International Prostate Symptom Score according to the presence of a previous urological symptom. Notes: Repeated measures two-way ANCOVA with post hoc test. Age was included as a covariate. *Indicates a statistically significant difference at p≤0.05. SD Standard Deviation.

Duration	International Prostate Symptom Score (Mean + SD)			p-value
	Previous urological symptoms	No previous urological symptoms	Total
Before COVID-19 infection	6.52 ± 5.64	2.77 ± 3.014	5.41 ± 5.57	0.787 (Interaction)
During COVID-19 infection	10.98 ± 7.66	7.23 ± 6.01	9.65 ± 7.26
After 3 months	8.43 ± 6.80	5.50 ± 5.69	7.51 ± 6.61
After 6 months	9.59 ± 6.38	7.40 ± 5.23	8.92 ± 6.11
p-value	0.026*		0.000*

Correlation of IPSS with age of the patients:

The correlation between IPSS and age at different follow-up time intervals was assessed (Table 7). The findings reveal a consistent positive correlation between IPSS and age across the various stages of examination. Before COVID-19 infection, a moderate positive correlation (r = 0.413) was observed, indicating that as age increased, IPSS scores also increased. This correlation strengthened during COVID-19 infection (r = 0.568), suggesting a more pronounced association between age and IPSS during this period. Even after recovery, at both 3 months (r = 0.363) and 6 months (r = 0.333) post-infection, a positive correlation persisted, albeit with slightly weaker coefficients. The statistical significance of these correlations was supported by low p-values (p ≤ 0.001) for all time intervals. These findings highlight the influence of age on IPSS and suggest that age may be a relevant factor to consider in evaluating lower urinary tract symptoms in individuals, particularly those affected by COVID-19.

Table 7. Correlation of IPSS with age at different follow-up time intervals.

IPSS	Age
	Correlation coefficient (r)	p-value
Before COVID-19 infection	0.413	0.000*
During COVID-19 infection	0.568	0.000*
After 3 months	0.363	0.001*
After 6 months	0.333	0.000*

COVID-19 infection had a significant impact on the severity of LUTS in patients. Symptoms worsened during the infection and showed some improvement afterward, although they remained higher than before the infection. The severity of COVID-19 symptoms, age, and prior urological symptoms were associated with higher IPSS scores. These findings provide important insights for evaluating and managing patients with BPH in the context of COVID-19.

5. DISCUSSION

The study used the IPSS scoring system to evaluate the severity of LUTS in patients with COVID-19 symptoms. A study by Kaya et al. (21) concluded that lower urinary tract symptoms (LUTS), especially storage symptoms, are important early indicators for the timely detection of COVID-19 alongside other common symptoms. Although COVID-19 mainly affects the respiratory system, it can also have systemic effects. Urological manifestations of COVID-19, though rare, can serve as predictive markers of the disease. However, there are conflicting opinions regarding the prevalence and severity of LUTS as COVID-19 progresses. One study found results similar to ours, suggesting that the severity of COVID-19 correlates with LUTS scores, with urinary frequency, urgency, and nocturia being the most common symptoms (12). Our study is notable because of its six-month longitudinal follow-up, which is rarely available, and because it identified age and prior urological history as consistent predictors of persistent LUTS. This provides a valuable clinical contribution beyond previous confirmatory reports. Conversely, another study reported that increased LUTS in COVID-19 patients does not relate to disease severity (22). Nabeeh et al. (23) found that COVID-19 raises IPSS scores, influencing treatment options for BPH. They also observed that LUTS in BPH patients were significantly affected by COVID-19. A multivariate analysis showed that age, pre-COVID-19 IPSS, and prior urological symptoms predicted LUTS in COVID-19 cases. Additionally, Daryanto et al. (12) reported a positive linear relationship between COVID-19 severity and IPSS scores. In our current study, although patients had mild prostate symptoms, IPSS scores increased as COVID-19 progressed. A significant link between the average IPSS and the timing relative to COVID-19 infection was also identified.

Some urological symptoms have been reported during COVID-19 infection. These include hematuria, which is the presence of blood in the urine, as well as proteinuria, an excess of protein in the urine (24). Additionally, COVID-19 can lead to acute kidney injury (AKI), characterized by a sudden decline in kidney function, and may also increase the risk of urinary tract infections (UTIs) in certain individuals, particularly those with prolonged hospital stays or requiring urinary catheterization (25). In the current study, about three-fourths of the patients reported having nocturia before a diagnosis of COVID-19 and half of them suffered from symptoms of urinary urgency, and increased frequency. Moreover, these symptoms peaked during infection. Biochemical analysis of the patients was not assessed in the current study.

Age is a known risk factor for severe COVID-19 and its associated complications, including respiratory symptoms. However, its direct influence on urinary tract infections (LUTS) is still being explored. Older individuals are more likely to experience age-related changes in the urinary system, such as decreased bladder capacity, weakened bladder muscles, and increased prostate gland size in men. These changes can contribute to LUTS, including urinary frequency, urgency, nocturia, and incontinence. The COVID-19 infection’s physiological stress can exacerbate pre-existing LUTS. Moreover, hospitalization in elderly patients increases the risk of developing urinary tract infections (UTIs) and other urinary complications, such as frequency, urgency, and dysuria. In this context, our study observed a positive correlation between patient age and IPSS values at all stages of COVID-19 infection. Similar results were reported by Kaya et al. where a significant difference in storage IPSS in male participants before, during, and after COVID-19 was reported (21). These observations suggest that age is an important factor to consider when evaluating LUTS in individuals affected by COVID-19.

This study strengthens our understanding of how COVID-19 affects lower urinary tract symptoms (LUTS). Our longitudinal methodology provided a thorough understanding of the pandemic’s consequences by using the IPSS to measure the severity of LUTS in people with and without pre-existing urological problems. By measuring LUTS before, during, and after infection, we were able to separate the effects of COVID-19 from other variables, such as therapy. Significant IPSS alterations were observed in even non-critical COVID-19 individuals with minimal intervention, indicating that the virus may independently contribute to the development of LUTS. This study offers significant new knowledge about the urological effects of COVID-19 across a range of patient histories and disease severity.

Despite its many strengths, this study has limitations. The study featured a relatively small sample size of patients and was conducted in a single hospital, which may limit how well the results apply to other populations or healthcare settings. The findings may not represent the entire population with COVID-19 infection. Participants were enrolled based on their admission to the hospital with COVID-19, potentially introducing selection bias. Additionally, the IPSS was developed for men and has not been extensively validated in women, which can impact the accuracy of LUTS assessment in our female participants. Since the IPSS assesses prostate-related symptoms in males, it may not accurately reflect female LUTS, and female-specific issues such as pelvic floor problems or incontinence subtypes might be underrepresented. Originally designed to evaluate symptoms like incomplete bladder emptying, frequency, urgency, and weak stream, the IPSS has limitations when applied to women, as several studies highlight. It might not fully capture diverse causes of female LUTS, such as stress urinary incontinence, overactive bladder, or pelvic floor dysfunction, which differ from male-specific conditions (14, 18). While Okamura et al. (18) showed acceptable psychometric properties for the IPSS in women, its validation remains limited, especially regarding female-specific symptoms like incontinence, which the tool does not directly assess. This can lead to underreporting or misinterpretation of symptoms, skewing prevalence estimates and clinical evaluations (24). Moreover, the IPSS’s focus on obstructive symptoms may lead to an overemphasis on these in women, where storage symptoms are often more prominent, and its lack of female-specific normative data complicates accurate severity scoring (25). Cultural differences in symptom interpretation and the tool’s limited ability to reflect the psychosocial impact of LUTS in women further reduce its usefulness (14, 18). The IPSS should be used cautiously by clinicians and researchers working with women and should be supplemented with female-specific tools for a comprehensive evaluation of LUTS. The study also did not include a control group of individuals without COVID-19 infection. The absence of a non-COVID-19 control group weakens causal conclusions, as it remains unclear whether the observed changes in LUTS are specific to COVID-19 or could be due to other factors such as hospitalization, psychological stress, or other illnesses. Including a well-matched control group would have strengthened the ability to determine the specific impact of COVID-19 on LUTS.

The study did not include objective clinical measures such as post-void residual urine measurements, medication usage data, or biochemical parameters such as serum creatinine, C-reactive protein, and electrolyte levels that could affect LUTS severity. Furthermore, the study did not comprehensively assess comorbidities or other factors that could influence LUTS. The presence of comorbid conditions may confound the association between COVID-19 infection and LUTS severity. Moreover, the specifics of pharmacotherapy for urinary symptoms or the evaluation of residual urine were not explicitly mentioned. Medications can alter symptom severity, and residual urine indicates incomplete bladder emptying, both of which are crucial for accurate symptom assessment. Biochemical analysis, which could provide deeper insights into the mechanisms linking COVID-19 and LUTS, was also missing.

Another significant limitation of the study is that pre-COVID IPSS scores were based on retrospective patient recall instead of prospective assessment. Retrospective recall can lead to over- or under-reporting of symptoms despite efforts to minimize recall bias, including detailed symptom definitions, a structured IPSS questionnaire, and limiting the recall period to just before illness onset. This might exaggerate or understate the actual change in LUTS severity caused by COVID-19. Since COVID-19 emerged suddenly, it was not possible to collect prospective baseline data, and retrospective recall was the only feasible method to assess pre-COVID status. Another limitation is that there was no non-COVID-19 control group, which reduces causal inference. Overall, we somewhat mitigated this limitation by using a repeated-measures within-subject design, allowing participants to serve as their own controls over different time points. In addition, bias from retrospective recall of pre-infection LUTS was minimized by the IPSS framework, which stratified infective and pre-infective LUTs, and by a small recall period immediately before infection.

To ensure a thorough investigation and exclusion of COVID-19 in patients presenting with LUTS, testing protocols, detailed patient histories, comprehensive screening, and continuous monitoring are essential. Future studies should also incorporate real-time data collection tools such as bladder diaries via mobile app-s and standardized objective assessments from the beginning to accurately capture evolving symptom patterns. Additionally, research should include larger, more diverse samples from multiple healthcare settings, incorporate control groups, thoroughly evaluate comorbidities, document pharmacotherapy and residual urine, and include biochemical analyses to gain a more complete understanding of the relationship between COVID-19 and LUTS. Furthermore, future investigations should employ prospective longitudinal approaches to prevent bias from retrospective recall.

Looking ahead, it will be important to develop and implement urinary symptom monitoring during future pandemics or emerging infectious diseases, such as establishing telemedicine-based LUTS surveillance protocols, periodic objective evaluations, and integrating digital health platforms for early detection and management of urinary complications populations who are at risk.

6. CONCLUSION

This study highlights the significant relationship between COVID-19 infection and the worsening of LUTS. Our findings demonstrate that LUTS severity increased during the infection period and showed only partial improvement post-infection, with symptoms remaining higher than baseline levels. The severity of COVID-19, along with factors such as age and prior urological conditions, correlated with higher IPSS scores. These results highlight the need to consider urological manifestations when assessing patients with respiratory infections and other systemic illnesses. Further research is crucial to understand the mechanisms underlying these associations and to develop effective management strategies for patients experiencing LUTS, in the context of an infectious disease. A deeper understanding of how systemic infections impact LUTS will enhance patient care and improve outcomes. The future studies must incorporate female-specific tools in LUTS, arrange prospective collection of data before an infection and control groups. However, our study offers an important longitudinal data, indicating that LUTS can last months after COVID and clinicians should remain alert to them.

Abbreviations

The following abbreviations are used in this manuscript:

ACE2 Angiotensin-Converting Enzyme 2

IPSS International Prostate Symptom Scores

LUTS Lower Urinary Tract Symptoms

TMPRSS2 Transmembrane Serine Protease 2

PSA Prostate-Specific Antigen

Institutional Review Board Statement

This study was approved by the ethics committee at The Faculty of Medicine/Mutah University, Reference Number: 15052021. The study was strictly conducted as per the guidelines of the Declaration of Helsinki.

Informed Consent Statement

Written informed consent was obtained from all the participants.

Data Availability Statement

The data will be available for review by the corresponding author upon request.

Author Contributions

Author FS and Author GT conceived and designed the study, with Author FS developing the protocol and Author AT and Author SS refining the data-collection instruments; Authors MA, IA and MA collected and curated the data under supervision of Author FS and Author GT, which Author SS and Author TK then analyzed and validated; Authors TK and MA oversaw experimental execution and data integrity; Author FS drafted the initial manuscript, and Authors GT, SS, and TK critically revised it for intellectual content; Author AT prepared all figures and tables; Authors GT and FS supervised the project, provided mentorship, coordinated resources, and secured funding; all authors reviewed and approved the final version and agree to be accountable for all aspects of the work.

Conflicts of interest

The authors declare no conflicts of interest.

Financial support and sponsorship

This research received no external funding.