Pandemic: First Wave

During the first wave of COVID-19 pandemic in early 2020, New York City and Detroit were epicenters with high numbers of cases and death. We’d like to share with you our story of how we embarked on a research project during the darkest days of the pandemic and came to uncover the disease COVID-associated cystitis (CAC).

Dr Nivedita Dhar: “My husband and I are both physicians at the Detroit Medical Center. Strangely, in the first quarter of 2020, I was asked to consult patients with active or recovering COVID-19 with new onset, only after COVID-19 infection, of severe lower urinary symptoms (LUTS). I knew COVID-19 was affecting various organs and I began to wonder if it could affect the bladder. But how could I find out, as most everything at the Detroit Medical Center, including elective surgery and urology research, were shut down?”

Dr Sina Mehraban-Far, 2nd year urology resident at Wayne State University: “It is hard to believe that I am a pandemic generation physician. Finishing medical school in New York and starting my urology residency during the pandemic in 2021, I have seen the impact of COVID on patients and medical education, as well as delivery of care. So when Dr Dhar asked me if I was interested in working on a COVID urology research project I said, ‘Sign Me Up!’ ”

Table. Outcomes Assessment⁵

Dr Michael Chancellor, Professor of Urology, Director of the Aikens Research Center, Corewell Health Beaumont University Hospital: “My wife is a physician who specializes in public health, and I remember Ginny on New Year’s Eve 2019 saying to me, ‘Michael, there is a serious outbreak in Wuhan, China that you need to learn about. It is going to be big, and it is coming here. You need to prepare for it and get N95 masks.’ After my initial skepticism I started reading everything about COVID-19, like pretty much every health care provider in the world. I wanted to contribute but felt powerless, as most patient care and urology research was shut down. Then I started reading about cytokine storm and I had an idea, so I called Nivedita.

“I discussed with Nivedita that as cytokine storm is key to COVID-19 lethality, and that given one of our top research priorities in our lab at Beaumont Research Institute is focused on detecting urine cytokines for the diagnosis of interstitial cystitis, then we may be able to detect elevated cytokines in the urine of COVID-19 patients. I asked if she and her husband would be interested in a collaboration to collect urine in COVID patients for us to analyze for cytokines. Nivedita say yes and then told me she has been seeing urology consults of COVID patients with de novo LUTS, and wondered if I agreed with her that COVID-19 could affect the bladder. I said yes and that I also have been hypothesizing that COVID inflammation and cytokines in the urine can cause cystitis. We got off the phone and got moving, obtained IRB approval, and embarked on collection of urine from COVID-19 patients.”

We want to acknowledge that before publication of our work, Mumm and colleagues from Italy were the first to report increased urinary frequency in COVID-19 patients.¹ Mumm et al first observed increased urinary frequency in 7 males out of 57 patients admitted to their COVID-19 wards. These patients reported an average of 13.7 urinary voids per day on the day of admission and 11.6 on day 5.

Cystitis After COVID

In our initial report, we followed patients after their hospitalization from COVID-19 recovery and had a confirmed positive SARS-CoV-2 molecular diagnostic test.² Thirty-nine COVID-19-positive patients, including 7 females and 32 males, developed de novo urinary symptoms without urinary tract infection. Median length of stay was 10 days (range 5-30). All 39 patients completed the symptom score survey. All the patients had urge incontinence and 87% had 5 or more episodes of nocturia.

At the 2021 virtual AUA and in a subsequent publication,³ we reported the first study to assess pathophysiology of CAC. We hypothesized that CAC is caused by increased inflammatory cytokines that are released into the urine and/or expressed in the bladder (see Figure).⁴ Health care providers caring for COVID-19 patients should be aware of CAC, and de novo urinary symptoms should be included in the symptoms complex associated with COVID-19.

COVID Cystitis: Long Term

At the 2023 AUA meeting in Chicago, Dr Mehraban-Far presented the moderated poster “MP74-13 Long-term Outcomes of COVID-19 Associated Cystitis (CAC).”⁵ A total of 350 patients were identified with the diagnosis of CAC, of which 71% were newly diagnosed, and 29% with worsening overactive bladder symptoms 10-14 weeks after hospitalization with COVID-19 and followed for 21 to 28 months (see Table). No differences were noted among improvements in symptoms between females and males.

Dr Dhar reported, “We feel this study is important because it is the first long-term follow-up of patients who developed CAC and assessed the prognosis of CAC in long COVID. We found that after 21-28 months, only 13% of patients had persistent LUTS. Patients with long COVID and CAC may be reassured that symptoms resolve in the vast majority of cases and that supportive and reversible treatment should be recommended. So please hold off on neuromodulation or botulinum toxin injection. It was concerning that all 40 patients who had persistent urinary symptoms after 2 years were over the age of 65. We know COVID-19 hit the elderly the hardest and more research is needed on CAC in older Americans.”

Upon reflection of what has transpired since the beginning of the pandemic, Dr Chancellor recounted, “It was so depressing during the first wave of the pandemic being unable to help. Then an opportunity to connect urology research and COVID-19 appeared. I am grateful to the students, residents, fellows, nurses, scientists, and clinicians who came together, and thank God that nobody got sick collecting the urine samples. We have heard from many urologists from across the nation and around the world who told us that they have also seen CAC patients and found our research and just wanted to reach out. We thank you for sharing your stories.”