Impact of preoperative SARS-CoV-2 infection on post-prostatectomy urinary continence and erectile function

Introduction

Urinary incontinence (UI) and erectile dysfunction (ED) are among the most common complications following radical prostatectomy (RP), with estimated incidence rates of approximately 40–50% and up to 80%, respectively (1). Postoperative functional recovery is influenced by multiple factors, including patient age, tumor stage, nerve-sparing status, and individual anatomical variations such as urethral sphincter length and neurovascular bundle (NVB) integrity (2). Additionally, systemic inflammatory responses and vascular endothelial dysfunction have been proposed as key biological mechanisms contributing to postoperative functional impairment, particularly through their effects on neurovascular integrity and microvascular perfusion (2,3). Additionally, postoperative ED has been mechanistically linked to cavernous nerve injury-induced penile hypoxia, resulting in smooth muscle apoptosis, fibrosis, and veno-occlusive dysfunction, with further contributions from oxidative stress and endothelial dysfunction (4). Disruption of the anatomical integrity of the urethral sphincter complex and its supporting structures directly compromises continence mechanisms and contributes to postoperative UI (5).

Notably, since the coronavirus disease 2019 (COVID-19), pandemic, the potential impact of viral infection on postoperative complications has garnered increasing attention. Emerging evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infection may exacerbate neurovascular repair barriers through angiotensin-converting enzyme 2 (ACE2) receptor-mediated vascular endothelial injury and cytokine storms, which has been linked to male infertility and ED (6). However, high-quality evidence remains scarce regarding whether COVID-19 influences long-term functional recovery after RP, particularly for UI and ED. In this study, we retrospectively investigated the association between preoperative SARS-CoV-2 infection and urinary continence and erectile functional recovery after RP, to provide evidence for tailored postoperative management in COVID-19 infected patients. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-345/rc).

Methods

This retrospective cohort study enrolled patients with prostate cancer who underwent either laparoscopic or robot-assisted RP at West China Hospital between September 2022 and June 2023. Patients who had previously undergone prostate surgery [e.g., transurethral resection of the prostate (TURP)], received radiation therapy or androgen deprivation therapy, or were unwilling to provide required information were excluded. Clinical and pathological data collected included age, body mass index (BMI), preoperative prostate-specific antigen (PSA) level, Prostate Imaging Reporting and Data System (PI-RADS) score, and preoperative COVID-19 status. All patients were enrolled after December 2022, when COVID-19 restrictions in China had been lifted. RP was typically performed within 3–5 days of admission. Surgery was not routinely delayed until a negative test result; however, patients with pronounced respiratory or systemic symptoms, or those unwilling to proceed, were deferred until recovery. All procedures were undertaken only after anesthesiologic evaluation confirmed the absence of conditions that could compromise perioperative safety. During hospitalization, all patients underwent daily preoperative SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing (nasopharyngeal or oropharyngeal swabs). Patients were classified as COVID-19-positive if they had at least one positive RT-PCR result prior to surgery; otherwise, they were assigned to the COVID-19-negative control group (n=132). Six months after surgery, functional outcomes were assessed using validated questionnaires. Urinary continence was evaluated with the Incontinence Quality of Life (I-QOL) questionnaire, a 22-item patient-reported instrument measuring the impact of UI across three domains (avoidance and limiting behavior, psychosocial impact, and social embarrassment) (7). Erectile function was assessed with the five-item International Index of Erectile Function (IIEF-5), which yields a total score ranging from 5 (indicating severe ED) to 25 (normal erectile function) based on patient responses related to erectile confidence, ability to penetrate, maintenance of erections, difficulty, and satisfaction with intercourse (8). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was completed under the supervision and guidance of the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (No. 2024-1098). Written informed consent was obtained from all participants and, when applicable, their legally authorized representatives. Patients with incomplete follow-up data or missing outcome measures at 6 months were excluded from the analysis to ensure data completeness and accuracy.

This was a retrospective single-center study. To reduce potential selection bias, consecutive eligible patients were included. Baseline demographic and clinical characteristics were compared between groups to confirm comparability (see Table 1). Information on NVB preservation status (bilateral, unilateral, NVB not preserved, or missing) was extracted from operative records when available, and summarized in Table S1.

Statistical analysis

Clinical and demographic variables were summarized as frequencies and percentages for categorical data, and as medians with interquartile ranges (IQRs) for continuous data. The Shapiro-Wilk test was used to assess normality. For normally distributed data (P≥0.05), Student’s t-test or analysis of variance was applied; for non-normal data (P<0.05), the Mann-Whitney U test was used. Categorical comparisons were performed using the Chi-squared or Fisher’s exact test. Spearman correlation was used to evaluate associations between clinical variables and postoperative outcomes. Multivariable linear regression identified predictors of postoperative urinary continence and erectile function, with model assumptions assessed via variance inflation factor and residual analysis. Model fit was evaluated using R² and adjusted R², and regression coefficients were reported with 95% confidence intervals and P values (P<0.05). Additionally, Pearson correlation and stratified multivariable regression were used to assess the association between postoperative IIEF-5 and I-QOL scores by COVID-19 status, adjusting for potential confounders. To formally compare correlation strength between groups, Fisher’s r-to-z transformation was applied. Furthermore, an interaction term (IIEF-5 × COVID-19 status) was included in a multivariable linear regression model adjusted for age, BMI, PSA, Gleason score, PI-RADS score, and pathological stage to test whether the IIEF-5-I-QOL association differed by COVID-19 status. Because NVB preservation status was incompletely documented, it was not included as a covariate in multivariable models. At our center, postoperative rehabilitation for patients diagnosed with ED was initiated after functional assessment. Management strategies included early use of phosphodiesterase type 5 inhibitors, structured pelvic floor and sexual rehabilitation training, and psychological support when indicated. These interventions were part of routine clinical care and were not included in the outcome analysis of this study. All analyses were performed using Statistical Package for the Social Sciences v21.0.

Results

After rigorous prescreening based on the predefined inclusion and exclusion criteria, 152 of the initial 516 eligible patients were excluded for not meeting the inclusion criteria, and 30 patients did not undergo prostatectomy. Among the remaining 334 patients, 36 (10.8%) were lost to follow-up, resulting in a final study cohort of 298 patients (follow-up rate: 89.2%). Based on preoperative RT-PCR results, 166 patients were assigned to the COVID-19 group and 132 to the control group. Baseline demographic and clinical characteristics are summarized in Table 1. The median follow-up time for the final cohort was 6 months. No statistically significant differences were observed between the two groups in age, BMI, preoperative International Society of Urological Pathology (ISUP) grade, pathological T stage, or PI-RADS score (all P>0.05), although the COVID-19 group showed slightly higher preoperative serum PSA levels.

Regarding postoperative urinary continence, no statistically significant differences were observed in total I-QOL scores or its subdomains—including avoidance and limiting behavior, psychosocial impact, and social embarrassment—between the COVID-19 and control groups (P>0.05, Table 2). In contrast, erectile function was significantly lower in the COVID-19 group, with a reduced IIEF-5 score compared to the control group, indicating a greater degree of postoperative ED among patients with prior COVID-19 infection.

Correlation analyses between clinical variables and postoperative functional outcomes are presented in Table 3. Lower IIEF-5 scores were significantly associated with older age, higher preoperative PSA, higher ISUP grade, and more advanced pathological stage (all P<0.05), while BMI and PI-RADS score showed no significant correlation. Similarly, lower I-QOL scores were significantly correlated with higher preoperative PSA, ISUP grade, and pathological stage (P<0.05), whereas age and BMI were not statistically associated.

Multivariate regression analysis (Table 4) identified older age and more advanced pathological T stage as independent predictors of both postoperative urinary continence and erectile function. Notably, older age alone was sufficient to independently predict postoperative ED, consistent with established evidence that age is one of the strongest determinants of post-RP sexual outcomes. In univariable analysis, COVID-19 status was associated with reduced IIEF-5 scores (P=0.03); however, this association was no longer statistically significant after multivariable adjustment (P=0.08), and COVID-19 status showed no significant association with I-QOL scores (P=0.46).

In correlation analyses, postoperative IIEF-5 scores were significantly associated with I-QOL scores in both COVID-19 patients (r=0.262, P=0.001) and control patients (r=0.218, P=0.01), as shown in Table 5. Fisher’s r-to-z transformation showed that the difference between these two correlation coefficients was not statistically significant (z=0.31, P=0.76).

We further tested for an interaction between IIEF-5 and COVID-19 status in a multivariable linear regression model adjusted for age, BMI, PSA, Gleason score, PI-RADS score, and pathological stage. The interaction term was not significant [β=−0.159, 95% confidence interval (CI): −0.530 to 0.212, P=0.40], indicating no evidence that the strength of the association between erectile and urinary function differed by COVID-19 status.

Discussion

In this study, we investigated the impact of preoperative COVID-19 infection on postoperative functional recovery in prostate cancer patients undergoing RP. Our analyses revealed that while urinary continence outcomes at 6 months were not significantly affected by prior infection, patients with a history of COVID-19 demonstrated worse postoperative erectile function in univariable analysis, but this association was no longer statistically significant after multivariable adjustment, indicating that COVID-19 status was not an independent predictor of ED. Furthermore, both urinary and sexual function recovery were significantly correlated in COVID-19-positive and COVID-19-negative patients; however, the difference in correlation strength between the two groups was not statistically significant. These findings provide novel insights into how prior viral exposure may shape post-surgical recovery trajectories, particularly for functions reliant on vascular and neuroendocrine integrity. The following sections explore in detail the potential mechanisms underlying these associations and their clinical implications.

Our findings demonstrate a significant association between preoperative COVID-19 infection and impaired postoperative erectile function. While the precise mechanisms remain to be fully elucidated, current evidence suggests that SARS-CoV-2 may affect sexual function through a range of biological and psychosocial pathways. Several studies have proposed biological and psychosocial mechanisms by which COVID-19 may impair erectile function. For instance, viral binding to ACE2 receptors on vascular endothelial cells has been shown to disrupt the renin-angiotensin system leading to oxidative stress and microvascular thrombosis, which may in turn compromise penile blood flow and reduce erectile capacity (9,10). Complementing this, inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha have been implicated in the activation of the nuclear factor kappa-B signaling pathway, resulting in oxidative injury and apoptosis of cavernous smooth muscle cells—particularly in severe infections (11). Additionally, IL-6-mediated JAK-STAT3 pathway activation upregulates adhesion molecules like vascular cell adhesion molecule-1, promoting platelet aggregation and further impairing endothelial integrity (5). These findings collectively suggest that vascular endothelial dysfunction may play a central role in COVID-19-associated erectile impairment. Beyond vascular mechanisms, endocrine disruption has also been observed. Several studies have reported decreased serum testosterone levels in patients following COVID-19 infection, possibly due to direct testicular involvement or hypothalamic-pituitary-gonadal axis suppression (12,13). Since testosterone is essential for normal erectile physiology, this hormonal dysregulation may further contribute to functional decline. Moreover, endothelial injury caused by SARS-CoV-2 may inhibit nitric oxide synthesis, a critical mediator of penile vascular relaxation (14). Finally, psychosocial factors—including heightened anxiety, depression, and reduced sexual activity—widely reported during the pandemic, have also been associated with sexual dysfunction in recovering patients (15). Taken together, current evidence supports a multifactorial model in which COVID-19 may affect erectile function through vascular, hormonal, and psychological pathways. However, in our cohort these effects did not remain as independent predictors after multivariable adjustment.

While our findings suggest that preoperative COVID-19 infection is associated with impaired erectile function, its impact on urinary continence appears limited. To date, only a limited number of studies have explored the relationship between COVID-19 and UI. Kaya et al. suggested that storage symptoms, such as increased urinary frequency and urgency, might be among the early manifestations of SARS-CoV-2 infection (16). However, these findings largely reflect acute-phase responses in non-surgical populations. Our data indicate that preoperative COVID-19 infection does not significantly affect postoperative urinary continence outcomes following RP, although it does appear to increase the risk of ED. Notably, older age consistently predicted postoperative ED, consistent with prior literature and international guidelines. In fact, the strong effect of age may partly explain why the association between COVID-19 infection and ED was attenuated in multivariable analysis. Unlike previous studies, our investigation focuses on patients with prostate cancer undergoing RP—a population inherently at risk for urinary and sexual dysfunction due to the surgical disruption of pelvic anatomy. Recovery in this cohort is multifactorial and often prolonged, complicating the isolation of COVID-19-specific effects. Notably, based on Expanded Prostate Cancer Index Composite urinary domain scores reported by Yaxley et al., urinary function shows substantial improvement within 12 weeks postoperatively, progressing from moderate impairment (mean score in the 70s at 6 weeks) to near-normal levels (low 80s) by three months (17). This early functional recovery window may have minimized the measurable impact of preoperative COVID-19, particularly given that urinary continence is more strongly determined by anatomical reconstruction and surgical technique than by systemic inflammatory or vascular factors (3). Notably, emerging studies on long-term sequelae of COVID-19 have highlighted the role of immune memory and epigenetic reprogramming of hematopoietic stem cells, which may lead to sustained monocyte activation and chronic endothelial dysfunction (18). This mechanism may help explain why postoperative recovery of erectile function—a process heavily reliant on vascular and neuroendocrine integrity—appears more vulnerable to prior COVID-19 infection than urinary continence, which is more dependent on structural and surgical factors. These observations raise important questions about whether urinary continence and sexual function recover independently or in parallel following surgery—especially in the context of prior COVID-19 infection—prompting further exploration of their potential interrelationship.

UI and ED are among the most common functional sequelae following RP, and increasing evidence suggests that their recovery may be interrelated. Both complications share common risk factors—including age, tumor stage, surgical technique, and perioperative NVB preservation—and involve overlapping pelvic anatomical structures and neurovascular pathways (19). Furthermore, psychological distress caused by persistent UI may exacerbate sexual dysfunction, while ED itself may negatively affect patients’ confidence and motivation during functional rehabilitation (20). In our study, postoperative IIEF-5 and I-QOL scores were significantly correlated in both COVID-19-positive (r=0.262, P=0.001) and COVID-19-negative patients (r=0.218, P=0.01). However, the difference in correlation strength between the two groups was not statistically significant (Fisher’s r-to-z test: z=0.31, P=0.76), and the interaction term in multivariable regression was also non-significant (β=−0.159, 95% CI: −0.530 to 0.212, P=0.40). These findings suggest that urinary and sexual function recovery are interrelated across all patients, but prior COVID-19 infection did not significantly modify this relationship.

There are several limitations in this study that include potential sources of bias, with selection bias inherent to the retrospective single-center design and information bias from self-reported functional outcomes. First, the retrospective and single-center design may introduce selection bias and limit the generalizability of our findings. Second, the sample size was relatively small, which may reduce the statistical power for detecting subtle associations, particularly in subgroup analyses. We did not assess preoperative IIEF-5, and thus cannot exclude the possibility that some COVID-19 patients already had ED before surgery. Third, although preoperative COVID-19 status was determined using RT-PCR, we did not record symptom severity, duration of infection, or whether patients were symptomatic versus asymptomatic at the time of testing, all of which may influence postoperative recovery. We were also unable to systematically assess NVB preservation status due to incomplete operative records. As NVB preservation is a key determinant of postoperative erectile function, this represents an important limitation of our study. To improve transparency, available data on unilateral, bilateral, and no NVB preservation have been summarized in Table S1. Finally, the study cohort consisted exclusively of patients undergoing RP, and the findings may not be generalizable to patients receiving other treatments for prostate cancer. Future research will aim to increase case numbers and include long-term follow-up data with particular emphasis on functional and oncological outcome.

Conclusions

Preoperative COVID-19 infection was associated with worse erectile function in univariable analysis, suggesting that patients with a history of infection may warrant closer postoperative monitoring of sexual recovery. Urinary continence outcomes at 6 months were not significantly affected by prior infection. Postoperative sexual and urinary function were significantly correlated in both groups, the strength of this association did not differ by COVID-19 status. However, age and pathological stage remained stronger predictors of functional outcomes, and further studies are needed to clarify the long-term impact of COVID-19 on recovery after RP.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-345/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-345/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-345/prf

Funding: This study was supported by the Sichuan Science and Technology Program (No. 2023NSFSC1864).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-345/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was completed under the supervision and guidance of the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (No. 2024-1098). Written informed consent was obtained from all participants and, when applicable, their legally authorized representatives.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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