A cohort study by medical researchers from the Department of Urology, Oakland University William Beaumont School of Medicine, Beaumont Hospital-Royal Oak, Michigan – USA has found that COVID-19 increases the incidence of cystitis, overactive bladder and other urinary issues.
Cystitis refers to infection of the lower urinary tract, or more specifically, the urinary bladder. It may be broadly categorized as either uncomplicated or complicated. Uncomplicated cystitis refers to lower urinary tract infection (UTI) in either men or non-pregnant women who are otherwise healthy.
Complicated cystitis, on the other hand, is associated with risk factors that increase the virulence of the infection or the potential of failing antibiotic therapy. This activity reviews the evaluation and treatment of cystitis and describes the role of the interprofessional team in the care of patients with this condition.
The study findings were published in the peer reviewed journal: European Urology Open Science.
Our study demonstrates CAC incidence of 36.6% among individuals with previous symptomatic COVID-19 infection, which involved de novo OAB in 22% of these cases. Symptomatic COVID infection was associated with a threefold greater risk of having worsening OAB symptoms in comparison to the COVID-negative cohort, while the risk was only doubled for those with asymptomatic COVID.
The average change in ICIQ-OAB score for our cohort was an increase of 6.5 points (121% increase) from baseline at the time of the study, with the greatest changes seen for frequency and urgency scores. Those who were COVID+ reported an average urinary frequency of 7–8 episodes/d, with urgency “occasionally” or “sometimes”.
This is less severe than reported by Lamb and colleagues : most patients in their study, assessed using the OAB tool , had a frequency of ≥13 episodes/24 h (84.6%) and nocturia of ≥4 episodes/night (87.2%). Mumm et al.  observed a notable increase in urinary frequency among patients with COVID-19.
After treating a male patient for suspected urosepsis who was later confirmed to have a negative urine culture and positive COVID-19 status, the authors retrospectively evaluated urinary symptoms in their COVID-19 cohort and found that 7/57 of their COVID patients had urinary frequency as a presenting symptom. Upper and lower urinary tract bacterial infections as causes were excluded via urine analysis and urinary viral RNA, serum creatinine, and prostate-specific antigen assays .
The exact pathophysiology of CAC is yet to be discovered, although others have hypothesized that the increase in systemic inflammation on COVID-19 infection can lead to bladder inflammation and thus bothersome urinary symptoms . It is well established that the primary cause of cystitis can be multifactorial (bacterial, viral, medication, chemicals, radiation, or idiopathic), but once the bladder mucosa is damaged, this can trigger a cascade of events including the release of proinflammatory cytokines.
Once released, these cytokines can activate afferent nerves and detrusor muscle contractions that produce bothersome LUTS. This has been shown by Tyagi et al. , who reported elevation of urinary cytokines such as MCP-1, sCD40L, IL-12 p70/p40, EGF, and IL-10 in patients with OAB. In those with interstitial cystitis, higher levels of IL-6, IL-8, and growth-related oncogenes were also detected in urine .
Analogously, other viruses, such as Epstein-Barr virus, cause solid organ inflammation (hepatitis, gastritis, interstitial cystitis) by inducing T-cell release of cytokines such as IL-8 and chemokine ligands CCL2, CCL3, CCL4, and CCL5 , . Specifically for SARS-CoV-2, infection has been linked to multisystem inflammatory responses: elevated IL-6 is the strongest prognostic factor for severity and a novel pediatric condition termed multisystem inflammatory syndrome has been identified , .
It is also possible that COVID-19 may directly affect urogenital organs given that SARS-CoV-2 binds to ACE2, which is found not only in the lungs, heart, and ileum but also in bladder urothelial cells at high expression levels . The potential impact of COVID-19 on urogenital pathology cannot be understated , and although the focus here is not on the mechanism of action, clinical outcomes are reported from the largest cohort to date. It is also likely that our cohort of health care employees has the professional knowledge to accurately answer the questionnaires.
Using data from the BLAST COVID database, the largest COVID serology study to date, we found no correlation between SARS-CoV-2 antibody levels and OAB symptoms among patients with a prior COVID-19 infection. Because the serology data were obtained before vaccinations were approved and available for mass inoculation (December 2020), antibody ratios >1.1 were indicative of infection regardless of symptoms.
Reiterating the current understanding of risks factors for COVID-19 severity, our study shows that high BMI and diabetes are significant prognostic factors for CAC. In a systematic review and meta-analysis, Zheng et al.  reported that baseline hypertension, diabetes, and cardiovascular and respiratory diseases portend the highest risk of severe COVID-19 infection in comparison to those with noncritical symptomatology. Wolff et al.  reported that smoking and obesity were the most common lifestyle factors found among infected patients. Higher BMI and diabetes are already well established as prognostic factors for OAB, so patients with these conditions are at higher risk of developing CAC.
Our study has several limitations. Our rate of COVID positivity (31.9%) is higher than rates reported in the literature, such as the seropositivity rate of 8.8% (1818/20 614) among health care workers in the BLAST COVID study  and the 9.2% seropositive rate among prevaccinated patients in Michigan Medicine, a primary regional health system, in a study by Zhao et al. , suggesting that our population may be self-selective.
In other words, those who were diagnosed with COVID, had COVID-like symptoms, or were seropositive were more likely to participate. Other limitations include the risk of recall bias given the retrospective nature of the study, which may have limited the extent of symptom reporting. Moreover, a positive correlation between psychological stressors and OAB symptoms has been established .
Given the increase in stress related to the pandemic, especially for health care workers , it is possible that these are additional confounding factors in the increase in OAB symptoms. Moreover, in our multivariate analysis of comorbidities the numbers of study participants with a positive COVID diagnosis who had chronic steroid use or a suppressed immune system were very low, so the findings for these groups in particular need validation.
Finally, our study did not perform urine studies to rule out infectious or inflammatory causes; hence, the term CAC may be a misnomer and COVID-related LUTS may be more accurate. Further research is necessary to better understand this mechanism of action for guiding proper diagnosis and effective treatment of the condition.