Review

Urol Int Received: July 12, 2020

Accepted: November 4, 2020
DOI: 10.1159/000512880 Published online: November 23, 2020

Challenges in Urology during the

COVID-19 Pandemic
Peng Jin a, b Hyusim Park c Sungyong Jung c Jayoung Kim a, d
       

a Departments
of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA;
b Department
of Urology, Shengjing Hospital of China Medical University, Shenyang, China; c Department of
 

Electrical Engineering, University of Texas at Arlington, Arlington, TX, USA; d Department of Medicine,
 

University of California, Los Angeles, CA, USA

Keywords eral coronaviruses have caused epidemics in various re-

COVID-19 pandemic · Test methods · Clinical challenges · gions of the world (in 2002–2003 there was the SARS-Cov
Urological diseases · Urologists epidemic in China and in 2012 there was the MERS-CoV
epidemic in Saudi Arabia). The appearance of the new
viral SARS-CoV-2 (COVID-19) strain in 2019 that origi-
Abstract nated in the Chinese region of Wuhan started a global
The COVID-19 pandemic has caused a global health threat. pandemic, afflicting over a million people and causing
This disease has brought about huge changes in the priori- over 50,000 deaths [1]. COVID-19 belongs to the
ties of medical and surgical procedures. This short review β-coronavirus family, and it is thought to have originated
article summarizes several test methods for COVID-19 that in bats. There is a noted similarity between the genomic
are currently being used or under development. This paper sequence of human COVID-19 and that of HKU9-1 in
also introduces the corresponding changes in the diagnosis bats; however, the intermediate host between bats and
and treatment of urological diseases during the COVID-19 humans has yet to be identified. COVID-19 is highly con-
pandemic. We further discuss the potential impacts of the tagious and it has 3 main routes for transmission, i.e., per-
pandemic on urology, including the outpatient setting, clin- son-to-person contact, aerosol, and touch. In addition to
ical work, teaching, and research. © 2020 S. Karger AG, Basel infecting the respiratory system, the virus also infects the
blood, digestive, and urinary systems. As a result, the
presence of the virus has been detected in fecal, blood,
and urine samples. COVID-19 can cause a variety of
Introduction symptoms, such as fever, dry cough, shortness of breath,
loss of appetite, and fatigue. Furthermore, hidden trans-
Coronaviruses are enveloped, positive-sense, and sin- mission can occur from asymptomatic individuals. The
gle-stranded RNA viruses that can be subdivided into 4 incubation period for COVID-19 ranges between 2 and
different classes, i.e., α, β, γ, and δ. In recent years, sev- 14 days.

karger@karger.com © 2020 S. Karger AG, Basel Jayoung Kim

www.karger.com/uin Departments of Surgery and Biomedical Sciences
Cedars-Sinai Medical Center, Davis 5071
8700 Beverly Blvd., Los Angeles, CA 90048 (USA)
Jayoung.kim @ csmc.edu
 How will life change during and after the COVID-19 tially, while IgG-IgM is very useful in monitoring con-
pandemic from the point of view of a urologist? In this firmed patients or identifying late-stage patients for the
short article, we will discuss the COVID-19 pandemic prevention of spread. As of May 17, 2020, there were 75
and its effects on the field of urology. different COVID-19 test kit products that were Emergen-
cy Use Authorization (EUA) approved [9].
Table 1 shows a list of clinically evaluated test kits ap-
Discussion proved by EUA with results from positive percent agree-
ment and negative percent agreement.
COVID-19 Examination
Common Test Methods Routine Blood Test for COVID-19
The general structure of coronaviruses includes spike COVID-19 can cause serological abnormalities. Some
glycoproteins, membrane proteins, nucleoproteins, and studies have shown that the levels of lymphocytes, plate-
genomic RNA [2]. To detect the novel SARS-CoV-2, nu- lets, hemoglobin, and albumin in COVID-19 patients are
cleic acid testing is the main technique for laboratory di- decreased while levels of glucose, lactate dehydrogenase,
agnoses [3]. Sample sources include sputum, throat interleukin-6, serum ferritin, C-reactive protein, ESR, al-
swabs, and lower respiratory system secretions. Other anine aminotransferase, aspartate aminotransferase, cre-
methods, such as virus antigen or serological antibody atine kinase, D-dimer, and serum procalcitonin are in-
testing, are valuable assays for detecting infection. The creased [10, 11]. However, these routine serological ex-
main sample source for these tests is blood. As with other aminations can only indicate infection and have poor
emerging viruses, the development of methods was only specificity, which means that they cannot be used to con-
able to begin after identification of the viral genome. firm any diagnoses of COVID-19.
Real-time reverse transcription-polymerase chain re-
action (RT-PCR) has become the standard method for Expression of ACE2 and TMPRSS2 in the Urinary
diagnosing COVID-19 due to its specificity, sensitivity, System and COVID-19
and simplicity. Zhang et al. [4] used RT-PCR to detect The human angiotensin-converting enzyme 2 (ACE2)
COVID-19 from throat and rectal swab samples from pa- gene is located on chromosome Xp22 and includes 18 ex-
tients. The virus was detected in both types of samples. ons [12]. Functioning as a typical zinc metallopeptidase,
Throat swabs are suggested to be more applicable in the the ACE2 protein contains 805 amino acids and is a type
early stages of infection, while rectal swabs are better for I integral membrane glycoprotein containing a single cat-
detecting late-stage infections [4]. alytic domain. In the renin-angiotensin system, ACE2 de-
Unfortunately, RT-PCR detection kits have many lim- grades angiotensin II, which is potent in vasoconstriction,
itations, such as long turnaround times, complex opera- proinflammation, and pro-fibrosis, converting it into
tional procedures, expensive equipment, technical per- Ang (1–7) which contributes to vasodilation, antiprolif-
sonnel requirements, false negatives, and so on [2]. As a eration, and apoptosis. Besides its systemic effects on
result, these limitations make RT-PCR unsuitable for rap- blood pressure regulation, ACE2 also regulates amino
id and simple diagnosis and screening of patients [5, 6]. acid absorption in the kidneys and gut and modulates the
On the other hand, the COVID-19 IgG-IgM combined expression of amino acid transporters.
antibody test can generate results within 15 min and it can COVID-19 has a specific spike protein 3-D structure
determine whether the viral infection occurred recently. that is characterized by a strong binding affinity to ACE2
It is easy to use, has a high sensitivity, and does not require receptors [13]. As a result, human cells that express ACE2
additional equipment [4]. This rapid detection method may act as target cells for COVID-19. Since COVID-19
has great potential benefits for the mass screening of CO- must bind with ACE2 first before entering the human host
VID-19 infections [7, 8]. cells, the distribution and expression of ACE2 may be crit-
The COVID-19 IgG-IgM combined antibody test kit ical for the target organ of infection [14]. It is known that
detects antibodies in the blood that are produced by the ACE2 is enriched in the heart, kidneys, and testes, and it
body’s immune system for a prolonged period of time af- is also broadly distributed in the lungs, liver, intestine, and
ter infection. However, further studies of IgG-IgM tests brain [15]. Therefore, COVID-19 mainly infects the respi-
are needed in order to validate that it provides a high ratory system. In addition to respiratory symptoms, the
enough specificity and sensitivity to be widely used [9]. common complications found in patients infected with
RT-PCR has more benefits when diagnosing patients ini- COVID-19 include acute cardiac and kidney injuries.

2 Urol Int Jin/Park/Jung/Kim

DOI: 10.1159/000512880
 Table 1. EAU-approved COVID-19 test kits

Test kit Detection type Manufacturer PPA (%)/NPA (%)

Xpert Xpress SARS-CoV-2 test RT-PCR Cepheid 98.3/100 [105]

ePlex SARS-CoV-2 RT-PCR GenMark Diagnostics 91.4/100 [105]
94.4/100 [106]
AllplexTM 2019-nCoV RT-PCR Seegene 100/94 [107]
Anti-SARS-CoV-2 rapid test IgG-IgM AutoBio 88.15/99.04 [108]

The transmembrane serine proteinase 2 (TMPRSS2) in semen has not been investigated [21]. There have been
gene was first identified on human chromosome 21 in few studies investigating the presence of SARS-CoV-2 in
1997 [16]. The full-length cDNA encodes a predicted 492 semen, and no solid reports on virus presence in semen
amino acid protein, which is anchored to the plasma are available. The small studies that have been done have
membrane and belongs to the TTSPs family (type II found no viruses in semen. The sample sources came
transmembrane serine proteases). In humans, TMPRSS2 from patients with acute infection and convalescence, as
is mainly expressed on prostate, pancreatic, and colon well as testicular biopsies from deceased patients [21, 22].
cells, but it can also be found in lung, liver, and kidney Moreover, a recent paper published in August 2020
cells [17]. The entry of SARS-CoV-2 into host cells de- showed no COVID-19 viral transmission during sexual
pends on the serine protease activity of TMPRSS283-87. contact or assisted reproductive techniques [23]. Only
Cells overexpressing TMPRSS2 are susceptible to SARS- one study detected the presence of SARS-CoV-2 in se-
CoV-2 infection [18]. The process by which SARS-CoV-2 men; however, the sample size was small and the possibil-
enters the host cell can be divided into 2 steps. In the first ity that the virus came from urine could not be ruled out
step the viral hemagglutinin protein attaches to ACE-2, [24]. The virus may persist in the prostate or urethra and
and in the second step the hemagglutinin is cleaved to be carried away by semen during ejaculation. Moreover,
activate the internalization of the virus. This second step patients with severe COVID-19 infection may have con-
depends on the expression of TMPRSS2 [19]. taminated specimens when collecting semen. So far, there
has been no report of SARS-CoV-2 RNA in the expressed
Fecal/Urine/Semen Test for COVID-19 prostatic secretions of COVID-19 patients [25].
COVID-19 is primarily transmitted through the respi-
ratory tract [19]. However, ACE2 expression patterns Gender and COVID-19
across different tissue types suggest the possibility of ex- So far, most countries with available data have report-
trarespiratory viral transmission through bodily fluids ed that men with COVID-19 have a greater severity of
[20]. The current focus has been placed mainly on viral illness and a higher mortality rate than women across all
clearance from respiratory secretions and little is known age groups [26]. Possible reasons for this disparity in-
about the possible concurrent presence and clearance clude gender-related differences in ACE2 receptors, im-
through bodily fluids. mune function, sex hormones, hygiene, habits, etc. [27].
At present, the virus is mainly detected by nasopha- In previous cases of pathogenic coronaviruses, this differ-
ryngeal/oropharyngeal swabs. In addition to nasopha- ence between men and women also existed. In the 2002–
ryngeal/oropharyngeal swabs, the presence of COVID-19 2003 SARS outbreak and the 2012 MERS outbreak, the
RNA has also been reported in fecal, urine, and blood mortality rate was comparatively higher in men [28].
samples. Feces appear to contain a high percentage of vi- The relationship between COVID-19 and ACE2 has
ral RNA, and the percentage of patients with viral RNA been described before. Studies have shown that men have
in urine and blood appears to be low. However, some more ACE2 receptors than women and they have a great-
studies have been contradictory; no COVID-19 RNA was er expression of ACE2 in the lungs and heart, which may
found in the urine of infected patients [21]. explain why men tend to have more serious disease [29].
Although this represents pertinent information relat- Differences in immune defense abilities may also lead to
ed to reproductive medicine, the presence of COVID-19 differences in COVID-19 outcomes between men and

Challenges in Urology during the Urol Int 3

COVID-19 Pandemic DOI: 10.1159/000512880
women. Compared to males, females usually produce (ART) [39]. ART includes intrauterine insemination, in
more robust innate and adaptive immune responses and vitro fertilization (IVF) injection, ovum collection, im-
respond more strongly to most invading pathogens [30]. plantation, transplantation, and tracking. This process
Sex hormones play a role in regulating the immune could expose infertile individuals to COVID-19 infection
system and they can cause differences in immune re- [40]. In addition to the risk of infection, the World Health
sponse between men and women. Generally speaking, Organization (WHO) published data showing that preg-
testosterone has an immunosuppressive effect, while es- nant women with COVID-19 are at greater risk of serious
trogen tends to enhance the immune response [31]. En- complications [41]. There are no clear answers as to
dogenous testosterone makes men more likely to have whether there is a risk of vertical transmission of CO­
more serious complications related to SARS-CoV-2 in- VID-19 from mother to fetus. At present, no such cases
fection. On the other hand, SARS-CoV-2 infection can have been reported. In a case in China, newborns were
lead to hypogonadism in men, and the reduction of an- infected with the SARS-CoV-2 virus 36 h after birth [42].
drogens may cause serious complications [32]. Given that However, it is unclear whether this was due to vertical
estrogen activates the immune system, higher estrogen transmission between mother and child [42].
levels can potentially have a protective effect [33]. Studies At present, most reports indicate that the symptoms of
have shown that exogenous estrogen therapy can elimi- pregnant women infected with COVID-19 are similar to
nate inflammation and reduce virus titers, thus improv- those of others, and there is no evidence showing that
ing survival [34]. The differences in hygiene and habits pregnant women or fetuses are at a higher risk [43]. How-
provide another explanation for the gender-related dif- ever, considering the initial data and the lack of compre-
ferences in SARS-CoV-2 infection. Studies have shown hensive understanding of the pathogenesis of SARS-
that women wash their hands more frequently than men CoV-2 during pregnancy, most human reproduction so-
[35], and men wear masks less than women [36]. These cieties have proposed postponing embryo transfer and
factors may explain the noted differences in COVID-19 delay of new treatment cycles.
rates and mortality between the sexes. The European Society of Human Reproduction and
The higher smoking rate among men may also be re- Embryology (ESHRE) issued a statement regarding CO-
sponsible for gender-related differences in COVID-19 VID-19 and pregnancies on March 14, 2020. So far, only
mortality. Smokers seem to have a higher risk of respira- a few cases of COVID-19 infection during pregnancy
tory infections. A study found that the expression of have been reported. Therefore, there is not enough infor-
ACE2 in Asian smokers is significantly higher than that mation available about the potential impact of COVID-19
in nonsmokers [37]. However, the current literature does infection in the early stages of pregnancy. Additionally,
not support smoking as a predisposing factor for SARS- drug treatment for severe COVID-19 cases may include
CoV-2 infection. Gender differences are also reflected in drugs that are dangerous or prohibited for use during
men’s underutilization of medical services and participa- pregnancy. The ESHRE recommends that all patients
tion in unhealthy habits, such as alcohol use and smoking. considering or planning to receive ART treatment, re-
These behaviors can cause a high blood pressure, cardio- gardless of whether they are diagnosed with or suspected
vascular disease, and other comorbidities associated with to have COVID-19 infection, should avoid pregnancy at
increased mortality from SARS-CoV-2. Because cells this time and consider delaying pregnancy by freezing oo-
overexpressing TMPRSS2 are susceptible to SARS-CoV-2 cytes or embryos to delay embryo transfer [44].
infection, and the expression of TMPRSS2 is regulated by In the latest guidelines updated in October 2020, the
androgen/androgen receptor (AR) signals, the expres- ESHRE divides the guidelines for ART services during a
sions of AR and TMPRSS2 are significantly positively viral pandemic into 2 core steps. The first step is to assess
correlated [38]. This may be a reason why there are more the impact of the current pandemic based on epidemio-
male patients than female patients [19]. logical factors. The second step is to take corresponding
measures based on this assessment [45]. See Table 2 for
Assisted Reproductive Technology and COVID-19 specific guidelines.
In light of the current COVID-19 pandemic and the On March 17, 2020, the American Society for Repro-
uncertainty of its impact on pregnant women, the Society ductive Medicine (ASRM) released a new document ti-
of Human Reproduction published recommendations tled “Patient Management and Clinical Recommenda-
for the management of patients undergoing infertility tions during the Coronavirus (COVID-19) Pandemic”
treatment through assisted reproductive technology [46]. The main recommendations are as follows:

4 Urol Int Jin/Park/Jung/Kim

DOI: 10.1159/000512880
Table 2. ESHRE guidance for safe ART services during the third phase of the COVID-19 pandemic

14-day COVID-19 case Impact on ART Recommended mitigation measures

notification rate per services
100,000

Reported cases, n Insignificant – Continue as per routine

– Follow regional and country-specific guidance

<20 Minor – Triage recommended for all patients

– SARS-CoV-2 testing for triage-positive patients
– Follow regional and country-specific guidance

20.0–59.9 Moderate – Routine triage for patients and staff and SARS-CoV-2 testing for triage-positive patients/staff
– Routine implementation of the code of conduct for staff and patients
– Follow regional and country-specific guidance
60.0–119.9 Major – Routine triage for patients and staff, and SARS-CoV-2 testing for triage-positive patients/staff
– Routine implementation of the code of conduct for staff and patients
– Remote consultation and counselling (telemedicine)
– Reduction of visits to the ART clinic
– Routine use of PPE for staff
– Face mask recommended for patients
– No accompanying persons allowed
– Follow regional and country-specific guidance

≥120.0 Critical – Routine implementation of the code of conduct for staff and patients
– SARS-CoV-2 testing of all patients and staff
– Remote medical advice and counselling (telemedicine)
– Reduced clinic visits
– Staff: routine use of PPE
– Patients: face masks recommended
– No accompanying persons allowed
– Laboratory: freeze-all policy to be considered
– Follow regional and country-specific guidance

• Suspend the start of new treatment cycles, including to tumor causes and in cases where delayed treatment
ovulation induction, intrauterine insemination, IVF, may be more harmful than continued treatment (i.e., pa-
retrieval and frozen-embryo transfer, and nonemer- tients with a low ovarian reserve).
gency gamete cryopreservation. During the pandemic, the IVF department should
• Strongly consider canceling all embryo transfers, encourage male patients to collect semen samples at
whether fresh or frozen. home and send them to the laboratory. However, semen
• Continue to care for patients who are currently “in cy- samples must also be considered as potential sources of
cle” or in need of emergency stimulation and cryo- infection during this process. Assessment of the pres-
preservation. ence of SARS-CoV-2 in semen is particularly important
• Suspend the selection of surgery and nonemergency for semen cryopreservation because storage in liquid ni-
diagnostic procedures. trogen retains the pathogenic properties of the virus
• Minimize interpersonal interaction and increase the [48]. Therefore, it is necessary to conduct large-scale
utilization of telemedicine. studies on currently infected patients to confirm or ex-
In June 2020, the ASRM published the fifth update of clude the risk of male gametes. These risks need to be
patient management and clinical recommendations dur- assessed for cryopreservation in liquid nitrogen or ART.
ing the viral pandemic [47]. For details, please refer to It should be noted that a vast majority of published re-
Table 3. ports so far suggest that there is no SARS-CoV-2 in se-
However, each organization has also stressed that men. Only 1 article mentioned the presence of the virus
treatment should be carried out in certain cases, such as in semen, but the report itself has some questionable fac-
those in which women are required to retain fertility due tors.

Challenges in Urology during the Urol Int 5

COVID-19 Pandemic DOI: 10.1159/000512880
Table 3. ASRM patient management and clinical recommendations during the coronavirus (COVID-19) pandemic: 5th update

Third-party reproduction Do not start a cycle where the intended parents and the pregnant carrier do not live in the same
country.
Fertility services for Take routine precautions; there is no data to support the need for medical staff to avoid infertility
healthcare workers treatment or pregnancy.
Having partners present The number of people in the ward must be limited, and partners are encouraged to use telephone or
when providing care video methods to participate in the escort.
Travel restrictions Where feasible, avoid using public transportation; if there is an emergency trip, you need to know the
new infection rate in the local area and destination; self-isolation should continue to be practiced as
much as possible.
Resumption of reproductive Reproductive surgery can be resumed in areas where the prevalence of the disease should be low
surgery (<l2%). Before any surgery that requires anesthesia, the patient should be checked for COVID-19
symptoms. Preoperative SARS-CoV-2 virus detection should also be strongly considered. If the virus
test is positive, the patient needs to be rechecked for negativity before scheduling surgery.
Aerosol-generating If aerosol-generating procedures must be performed urgently during the operation, except for the
procedures anesthesiologist and the technical or circulatory nurse, the operation team should consider leaving
the room immediately. Staff can wear appropriate, fully enhanced PPE. These precautions should be
taken regardless of whether the patient has a negative preoperative test result, is asymptomatic, or has
no test result at all.
IVF cycles During the oocyte retrieval process, all patients should wear medical-grade surgical masks. Any
planned embryo transfer should be delayed until the patient is SARS-CoV-2 negative.
Urgent surgical procedures Staff should use enhanced respiratory PPE.

The ASRM and the ESHRE provide differing opinions disciplinary IVF team showed that, except for cell-cell
on whether to perform SARS-CoV-2 testing on patients contamination, which is considered extremely unlikely,
and providers [49]. The ASRM points out that, based on patient-employee, employee-employee, and employee-
existing evidence, nucleic acid amplification testing- cell interaction periods are estimated to have a moderate
based testing should be considered before reproductive to high infection risk [50]. Therefore, routine SARS-
surgery or other aerosol-generating procedures. Howev- CoV-2 tests for patients and providers are necessary.
er, for antibody testing, ASRM believes that antibody test- Because SARS-CoV-2 is an enveloped RNA virus, it
ing should not be used in the decision-making of patients can maintain its viability even at low temperatures, which
or providers, and it should not change compliance with can lead to cross-contamination between samples [51]. In
personal protective equipment (PPE) guidelines. On the assessing potential cross-contamination during cryo-
other hand, ESHRE relies more on serological testing. It preservation and storage, the single recorded case of cross-
is recommended that, if either party develops symptoms contamination in tissue samples was hepatitis B in bone
within 2 weeks before ovarian stimulation, the SARS- marrow, which was transmitted to the recipient [52]. The
CoV-2 IgM/IgG test can be used to decide to continue or only known cross-contamination of tissues stored in IVF
postpone treatment until it is negative or negative. ASRM was experimental. Bielanski et al. [53] found that liquid
believes that the detection of SARS-CoV-2 antibodies is nitrogen intentionally contaminated with bovine viral di-
currently not part of the routine workflow of infertile pa- arrhea virus spread to 21.3% of nearby open storage de-
tients, but the ESHRE believes this is critical. vices. However, all sealed straws and freezing tubes were
In addition to COVID-19 infection from the provider, not contaminated. In another similar study, mouse em-
semen samples can become a potential source of infection. bryos were stored with murine virus vials and no cross-
There may also be a 1-way infection. Four main areas of contamination was observed even after a year in storage
potential 2-way infection have been identified, i.e., pa- [54]. These studies have shown that the risk of cross-con-
tient-staff, staff-staff, staff-cell, and cell-cell. The results of tamination in liquid nitrogen is indeed negligible, espe-
a failure modes and effect analysis conducted by a multi- cially when samples are stored and sealed properly.

6 Urol Int Jin/Park/Jung/Kim

DOI: 10.1159/000512880
 Due to the COVID-19 pandemic, medical institutions Urological Diseases and COVID-19
worldwide recommend performing surgical operations Guidelines Office of the European Association of
for only high-priority or emergency cases. Low priority Urology
cases, such as diagnostic semen analysis, sperm banks, The European Association of Urology (EAU) estab-
elective surgery for sperm retrieval, and related fertility lished a rapid reaction group after the virus outbreak to
procedures, have been delayed for 6 months or longer and develop adaptive guidelines to deal with various situa-
pose no increased health risks to individuals [55]. How- tions and priorities. They divided urological diseases and
ever, this pandemic may last longer than expected – po- conditions into the following 4 priority levels [55]:
tentially years. During this period, the average age of • Low priority: clinical harm very unlikely if postponed
women trying to conceive will increase and ovarian re- for 6 months
serve indicators will worsen. Contrastingly, male infertil- • Intermediate priority: clinical harm possible, but un-
ity is usually related to progressive testicular damage, likely, if postponed for 3–4 months
such as varicocele. The adverse effects of delayed future • High priority: clinical harm very likely if postponed for
ART treatments are a growing concern. With the suspen- >6 weeks
sion of treatments, patients feel more anxious and fearful • Emergency: life-threatening situation – cannot be
of impairments in possible future pregnancies [56]. postponed for >24 h.
Studies have shown that patients with reduced ovarian Evidence from Wuhan shows that the mortality rate of
reserves starting IVF treatment up to 180 days after the asymptomatic patients who tested positive for COVID-19
first visit will not have their pregnancies affected [57]. For after surgery was 20% [61]. Therefore, in the process of
high-risk patients with a poor response to ovarian stimu- treating patients, doctors should choose the appropriate
lation, this observation still applies. Providers and pa- treatment plan according to the priority level. The latest
tients should rest assured that, if short-term treatment guidelines provide some suggestions; for instance, sur-
needs to be delayed for medical, logistical, or economic gery can be performed on high-priority and emergency
reasons, the treatment results will not be affected [58]. patients during the COVID-19 pandemic, but surgery is
When treating varicocele, surgery is not the only method. not recommended for intermediate-priority patients.
Only when progressive testicular growth retardation and/ Next, we will introduce specific treatment plans for sev-
or semen quality is severely impaired should clinical var- eral common diseases in urology during the COVID-19
icocele surgery be performed to maintain fertility [59]. pandemic.
Recently, 27 experts from 15 different countries ex-
pressed that postponing andrology services and male in- Kidney Injury
fertility treatments during the pandemic may permanent- Since ACE2 is expressed in kidney cells, changes in the
ly damage the chances of having children for “time-sen- kidney due to COVID-19 need to have a point of focus
sitive” patients [60]. This can have devastating [17]. Renal functioning needs to be monitored regularly,
psychological effects. The birth window for time-sensi- especially in patients with elevated plasma creatinine lev-
tive patients is short and any delay can be impactful. Such els. In the event of early signs of acute kidney injury
patients can be grouped into the following categories: (AKI), interventions, such as continuous renal replace-
• Those with cancer and/or undergoing chemotherapy, ment therapy, should be implemented to protect renal
radiotherapy, or immunosuppressive therapy functioning as early as possible. A study by Pei et al. [62]
• Old age (>50 years) observed that COVID-19 patients have a high frequency
• Those with severe male infertility (e.g., men with azo- of renal abnormalities, including 75.4% of patients with
ospermia/cryptospermia undergoing medical or post- renal involvement, 65.8% with proteinuria, and 41.7%
surgical treatment to improve sperm quantity/quality) with hematuria.
• Those with inflammatory and systemic autoimmune The risk factors and causes of AKI in COVID-19 pa-
diseases. tients are diverse. The severity of pneumonia is the most
For such patients, the provision of andrology services important factor in the development of AKI in COV-
cannot be regarded as a low priority [56]. Therefore, some ID-19 patients. The basic pathophysiology of patients
experts believe that ART treatment can be carried out if with pneumonia is severe acute respiratory distress syn-
the patient is considered high priority and has signed in- drome, which has been identified as an independent risk
formed consent, agreeing to receive treatment and freez- factor related to AKI [63]. This data indicates that it is
ing procedures during a pandemic. necessary to provide in-depth support and careful moni-

Challenges in Urology during the Urol Int 7

COVID-19 Pandemic DOI: 10.1159/000512880
toring of COVID-19 patients with severe pneumonia to Bladder Cancer
improve their complications. However, in a study of 116 Patients with high-risk non-muscle-invasive bladder
COVID-19 hospitalized patients, Wang et al. [64] found cancer need to be revisited to receive Calmette-Guérin
that all patients without chronic kidney disease showed Bacillus (BCG) intravesical instillation to reduce progres-
no obvious abnormality of renal function, and none of sion and recurrence after transurethral resection of the
these patients showed AKI. Patients with chronic kidney bladder [66]. It has been reported that nearly 30% of pa-
disease who underwent CRRT were stable, without exac- tients over 65 years of age may develop acute respiratory
erbation of chronic kidney disease throughout the course distress syndrome after infection with COVID-19 [66].
of treatment of COVID-19. Most patients with non-muscle-invasive bladder cancer
have a higher risk of severe forms of COVID-19 and may
Renal Cancer need to enter the intensive care unit for invasive ventila-
The current COVID-19 pandemic is forcing medical tion because the median age of these patients is greater
staff to adapt their clinical practice, especially for the than 70 years [67].
management of life-threatening diseases, such as malig- In confirmed COVID-19 cases, due to the lack of data
nant urological tumors. It is important to weigh the risk on the tolerance of intravesical BCG, the recommended
of contamination related to treatment and the risk of de- and cautious approach is to delay additional instillation
laying treatment. of BCG. Based on the infection status of COVID-19, it is
The CCAFU recommendations for the treatment of recommended to delay the installation of BCG for at least
renal cancer during the COVID-19 pandemic are as fol- 3 weeks after initial symptoms appear to improve. When
lows [65]: dealing with side effects related to intravesical BCG infu-
• Small T1a tumors, cystic tumors (Bosniak III and IV), sion, attention should be paid to persistent fever by isolat-
and T1b tumors: surgery should be postponed under ing and testing for COVID-19 [11]. Additionally, al-
supervision though side effects should be specifically treated ac­
• CT2 tumors: surgery can be postponed under quar- cording to current EAU guidelines, nonsteroidal anti-
terly supervision inflammatory drugs should only be used in patients with
• T3 tumors, thrombus of the renal vein, vena cava no COVID-19 infection because these drugs may lead to
thrombus, macroscopic lymphadenopathy without a higher risk of hospitalization and intensive care unit ad-
other secondary lesions, signs of locoregional inva- mission [66].
sion, and symptomatic tumors (pain, hematuria), for
which no endoscopic or vascular treatment is possible: Prostate Cancer
surgery must be maintained as a priority Surgery is recognized as the gold-standard treatment
• Indications of cytoreductive nephrectomy: favor ac- for several malignancies, including prostate cancer (PCa).
cording to the prognostic stage, monitoring, or medi- With all healthcare systems and resources focused on
cal treatment controlling and treating COVID-19, oncologic surgery
• Metastatic renal cancer with a good prognosis: favor a has been reduced worldwide. Surgery is associated with a
tyrosine kinase inhibitor by encouraging telephone higher overall and cancer-specific survival compared to
follow-up or teleconsultations radiation therapy alone. Apart from the theoretical ad-
• Metastatic renal cancer with a poor or intermediate vantage of radiation therapy in eliminating local micro-
prognosis: the benefits of current standard treatments metastases, clinical evidence shows that a real multimod-
based on a ipilimumab-nivolumab combination must al approach is best for patients choosing to undergo radi-
be weighed against the risk of severe toxicity in the cal prostatectomy [68]. Delay in the detection or treatment
context of reduced access to an intensive care unit. The of PCa can lead to impaired functional outcomes and
use of sunitinib by default is suboptimal but can be higher rates of biochemical recurrence [69].
discussed in this context. Patients who have an inter- Surgery should only be performed in sterile COVID-
mediate prognosis with a low tumor load and are as- 19-free facilities; otherwise, according to reports from
ymptomatic can be treated with tyrosine kinase inhib- Wuhan, postoperative mortality can reach 20% [61]. Un-
itor. For patients with a poor prognosis and in poor fortunately, the preservation of such facilities is impos-
general condition (PS ≥2), exclusive palliative treat- sible. According to the Italian experience, both asymp-
ment may be preferred. tomatic caregivers and patients can be a source of infec-
tion, causing further spread within the hospital [70]. To

8 Urol Int Jin/Park/Jung/Kim

DOI: 10.1159/000512880
maintain a truly COVID-19-free facility, preoperative or even been canceled. The latest EAU guidelines recom-
isolation and laboratory testing are needed to ensure that mend the implementation of telemedicine during this
staff and patients have no infections. time [55]. The development of telemedicine has been a
Recently, studies have pointed out that there may be a pragmatic approach to reducing the risk of further trans-
potential link between PCa and COVID-19 [71]. A study mission. Nonemergency patients, such as those with fol-
showed that PCa patients who received androgen depri- low-up tumors, benign conditions (such as moderate
vation therapy had a 4-fold risk of SARS-CoV-2 infection lower urinary tract symptom and prostate enlargement),
than those who did not receive androgen deprivation and urinary tract infections, can be given a consultation
therapy [71]. So far, there are 2 main genes related to the over the telephone. Clinical priority should be given to
entry of the COVID-19 virus into host alveolar epithelial patients with a suspected relapse or new malignant tu-
cells, i.e., ACE2 and TMPRSS2. The expression of TM- mors, severe lower urinary tract syndromes, or potential
PRSS2 is regulated by androgen/AR signaling. In primary obstructive/purulent urinary tract stones and those need-
and metastatic castration-resistant PCa, the expressions ing an immediate postoperative examination [78].
of AR and TMPRSS2 were significantly positively corre- If a face-to-face interview is needed, both the provider
lated [72]. These findings indicate that more androgens and the patient need to wear masks and maintain social
may mean an increased expression of TMPRSS2, which distancing [79]. Patients should also answer questions
may increase the susceptibility to SARS-CoV-2. Interest- about their COVID-19-related exposure history or symp-
ingly, a recent study showed that ACE2 expression is toms [80]. Patients with a positive screening are referred
higher in men and may be regulated by androgen/AR sig- to isolated treatment. In the case of a negative screening,
naling [73]. Therefore, androgen deprivation therapy can clinicians and patients must be provided with infection
have a potential curative effect on COVID-19. control procedures throughout the length of care.
Due to technological improvements and cost reduc-
Effects on the Testes tions as well as the widespread popularity of high-speed
The testes may be affected by COVID-19. A study re- internet and smartphones, patients can quickly deploy
ported that 19% of COVID-19 men suffer from scrotal telemedicine consultation from home [81]. The benefits
discomfort, suggesting viral orchitis [74]. Orchitis has not of telemedicine include convenience, access to care from
been confirmed as a possible complication of SARS- a distance, and lower medical costs. At the same time, it
CoV-2 infection. The virus may not directly infect the can reduce contact with patients and potential infection.
testes, but it may trigger a secondary autoimmune re- Providers in quarantine or isolation can also continue to
sponse that can cause autoimmune orchitis. COVID-19 work [82]. One of the main disadvantages of telemedicine
is related to abnormal blood clotting, so orchitis could is that consumers lack awareness of its use, services, and
also be the result of segmental vasculitis. A recent study costs. In addition, the lack of physical contact between
provided insight into impaired male gonadal function af- patients and doctors also poses challenges when conduct-
ter COVID-19 infection [75]. That study showed that the ing remote physical examinations. Most countries lack a
testosterone-to-luteinizing hormone ratio in 81 patients regulatory framework to authorize, integrate, and reim-
with COVID-19 was dramatically decreased in compari- burse telemedicine care for all patients, especially in
son to 100 age-matched healthy counterparts [76]. The emergencies and outbreak situations [83].
serum testosterone-to-luteinizing hormone ratio could When it comes to face-to-face medical consultations,
be a potential marker of impairment of reproductive the effects of facial coverings by masks can have a signifi-
health caused by COVID-19. Another study also con- cant negative impact on patients [84]. The “distance” ef-
firmed that the serum LH level of patients with CO­ fect produced by maintaining social distancing requires a
VID-19 was significantly higher than that of healthy men louder voice for communication, which in turn may harm
with normal fertility, while the ratio of serum testosterone patient privacy and reduce patient satisfaction [85].
to luteinizing hormone was significantly decreased, which
is indicative of subclinical hypogonadism [77]. Urological Surgery
Most benign urological surgeries, including surgeries
Effects of the COVID-19 Pandemic on Urologists for incontinence, benign prostatic hyperplasia, recon-
Outpatient Care struction, infertility, erectile dysfunction, and genitouri-
Due to the increased spread of the pandemic over time, nary prolapse [86], should be postponed until the pan-
in-person visits in the outpatient setting have decreased demic is over.

Challenges in Urology during the Urol Int 9

COVID-19 Pandemic DOI: 10.1159/000512880
 Ficarra et al. [86] and Stensland et al. [87] proposed should receive a preoperative COVID-19 test. For pa-
excellent recommendations for urological practice dur- tients without any clinical symptoms and no history of
ing the COVID-19 pandemic. With regard to urinary contact with COVID-19-positive patients, it is recom-
tract obstruction or infection, ureteral stents or neph- mended that they undergo a COVID-19 test within 48 h
rostomy tubes under local anesthesia should be firstly before surgery. In general, medical staff should use com-
considered. If this is not possible, stents under general plete PPE regardless of the patient’s COVID-19 status.
anesthesia should be the next option. Acute urinary re- Patients also need to wear a full set of PPE if they are
tention can be managed through insertion of a urethral found to be positive for COVID-19. The operation should
or suprapubic catheter under local anesthesia. In cases be performed by experienced surgeons and all unneces-
of clot retention due to bladder cancer or PCa, a cysto- sary personnel should remain outside the operating
scopic evacuation should be considered and transure- room. Electrocautery devices should be used on reduced
thral hemostasis of the tumor should be done to avoid power settings to decrease the generation of surgical
the need for blood transfusions. Additionally, interven- smoke. Flushing fluid should be collected through a
tions should only be considered for pediatric urological closed system during the urological procedure. Elderly
emergencies, such as acute torsion (implement scrotal patients with comorbidities, even in high-priority cases,
exploration and orchidopexy) and genitourinary ob- should be carefully considered for surgery. If a surgical
struction (consider a Foley catheter and a suprapubic patient is diagnosed with COVID-19, a special operating
tube). In patients with a genitourinary trauma, surgical room must be prepared.
exploration is recommended only in hemodynamically
unstable patients [87]; otherwise, procedures that can be Organ Transplantation in Urology
performed with local anesthesia may be used. Lastly, the Patients with end-stage kidney disease are at a higher
authors recommend immediate intervention for pa- risk of contracting infectious diseases due to their intrin-
tients with refractory priapism (consider shunting), a sic fragility caused by their defective immune system [90].
scrotal abscess or Fournier gangrene (consider drainage Although there is no evidence that COVID-19 is trans-
and debridement, respectively), and an infected artifi- mitted through organ donations, this cannot be ignored
cial urethral sphincter or penile prosthesis (removal of because the virus has been detected in approximately 15%
the infected device) [86, 87]. of patients [91]. The Transplant Association recommends
Aerosol transmission of COVID-19 cannot be ignored COVID-19 testing of donors suspected of having the vi-
because it can survive in the environment for 3 h [88]. rus, coming from endemic areas, or having a history of
Because of this, it is recommended to use the lowest intra- possible contact [92]. Special care should be given solid
abdominal pressure on the pneumoperitoneum during organ transplant recipients as they are usually under
robotic or laparoscopic surgery to reduce the risk of med- chronic immunosuppression, which puts them at a high-
ical staff aerosol infection. Zheng et al. [89] recommend er risk of COVID-19 infection. On the other hand, the
using lower power settings on electrocautery since ultra- safety of the transplantation team is another concern;
sonic scalpels or electrical devices may produce a large they can be exposed to transplant recipients who may po-
amount of surgical smoke. Additionally, adequate and tentially harbor higher viral loads than that of normal
complete deflation of the pneumoperitoneum may re- contact [91]. Therefore, the transplantation team must be
duce the risk of infection. All console surgeons should cautious in areas with widespread community diffusion
wear goggles or sealed sunshades and carefully disinfect of COVID-19. In such situations, the US Organ Procure-
the console’s head support between shells. Furthermore, ment and Transplantation Network suggests following
it is recommended that endoscopic procedures and ure- CDC recommendations when evaluating suspected CO-
thral catheterization be performed with caution, and sur- VID-19 patients (mask the patient, place the patient in an
geons should be completely protected against infection if isolation room, medical personnel must take airborne
the patient has suspected or confirmed COVID-19 [86]. and contact precautions when contacting the patient, and
In the latest EAU guidelines [55], there is some guid- inform the local authorities about the case) [93].
ance on preoperative management, general surgery, and
surgery for COVID-positive patients during the COVID Training for Urologists
pandemic. For example, in the preoperative stage, pa- The COVID-19 pandemic has influenced residency
tients with clinical symptoms and/or those who have training programs and medical graduate education. Most
been in contact with COVID-19-positive individuals clinical rounds are canceled in many countries. Medical

10 Urol Int Jin/Park/Jung/Kim

DOI: 10.1159/000512880
training programs and teaching activities have switched using the “molecular clamp,” a transformative technolo-
to online platforms. For instance, in Singapore, interhos- gy [102]. Inovio Pharmaceuticals, in collaboration with
pital staff movement among hospitals has been put on Beijing Advaccine Biotechnology, has started preclinical
hold, while residents training in other hospitals will stay trials for a DNA vaccine (INO-4800) against SARS-
there indefinitely [94]. However, efforts are being made CoV-2 [103]. Moderna, Inc., has started phase I clinical
to ensure that these actions do not harm the long-term trials for mRNA-1273, an mRNA vaccine, encoding the
needs of medical trainees. Attention must be focused on viral spike (S) protein of SARS-CoV-2 [104].
how the COVID-19 pandemic and its effects, including
the suspension of all nonemergency elective procedures,
delay of inpatient examinations, and cessation of clinical Conclusions
rounds, may have a stressful impact on residents and stu-
dents [95]. The COVID-19 pandemic is the biggest modern chal-
lenge facing the global healthcare system. After the pan-
Clinical and Lab-Based Urological Research demic, how will COVID-19 transform urological practice
During the first stages of the COVID-19 outbreak, and research? Due to the limited supply of ventilators,
many researchers focused on researching the treatment manpower, and hospital resources, there is an urgent
and prevention of the virus. Currently, there are no ap- need to establish a new set of systems to meet demands in
proved therapies or vaccines. Several national and inter- emergencies, such as replacing traditional outpatient ser-
national research groups are working collaboratively on vices with telemedicine, reducing the number of nonnec-
a variety of preventative and therapeutic interventions. essary operations, and implementing network teaching.
Some potential antiviral drugs, including nucleoside ana- In relation to urology, it is necessary to strengthen the
logs, chloroquine, and protease inhibitors, are being ur- safety training of medical staff. Since exposure to patients
gently administered to patients with COVID-19 [3]. and bodily fluids presents potential increased risks of vi-
Favipiravir (T-705) is a guanine analog. A recent ral transmission, medical staff must be adequately pro-
study suggested that favipiravir is a potential candidate tected. The concern of renal damage in patients from CO-
for treating COVID-19, showing effective antiviral ac- VID-19 also requires much attention. Lastly, it is impera-
tivities in Vero E6 cells [96]. Remdesivir (GS-5734) is an tive to channel international resources into high-quality
adenine analog. Remdesivir has emerged as the most clinical trials with robust scientific rationale and vigorous
promising candidate for the treatment of COVID-19 in- statistical rigor to overcome this pandemic.
fection [96]. Both lopinavir and ritonavir are protease
inhibitors and have been reported to have antiviral ac-
tivities against SARS and MERS [97, 98]. For treatment Acknowledgement
of COVID-19, clinical trials (ChiCTR2000029539) have
been initiated to test the antiviral activity of these prote- This research was supported by the Samuel Oschin Compre-
hensive Cancer Institute (SOCCI) at Cedars-Sinai Medical Center
ase inhibitors in patients [99]. However, the antiviral ef-
through the 2019 Lucy S. Gonda Award.
ficacy of HIV protease inhibitors in coronavirus prote-
ases is controversial.
Vaccines are the most effective strategy for preventing
Conflict of Interest Statement
infectious diseases because they are more cost-effective
than treatments and can reduce morbidity and mortality The authors have nothing to disclose.
without long-lasting effects. However, there are still no
approved vaccines for human coronaviruses. Research
groups around the world are accelerating the develop- Funding Source
ment of COVID-19 vaccines using various approaches,
including vaccination based on subunit, DNA, and This research was funded by the National Institutes of Health
mRNA [100]. (1U01DK103260, 1R01DK100974, U24 DK097154, and NIH
Clover Biopharmaceuticals is conducting preclinical NCATS UCLA CTSI UL1TR000124), the Department of Defense
(W81XWH-15-1-0415 and W81XWH-19-1-0109), the Centers
testing of a recombinant subunit vaccine based on the tri- for Disease Control and Prevention (1U01DP006079), and the US-
meric S protein (S-Trimer) of SARS-CoV-2 [101]. The Egypt Science and Technology Development Fund by the Nation-
University of Queensland is developing subunit vaccines al Academies of Sciences, Engineering, and Medicine (all to J.K.).

Challenges in Urology during the Urol Int 11

COVID-19 Pandemic DOI: 10.1159/000512880
This article is derived from the subject data funded in whole or part Author Contributions
by the National Academies of Sciences, Engineering, and Medicine
(NAS) and the United States Agency for International Develop- Research conception and design: J.K. Data analysis and inter-
ment (USAID). Any opinions, findings, conclusions, or recom- pretation: P.J. and H.P. Drafting of this paper: P.J., S.J., and J.K.
mendations expressed in this article are those of the authors alone Supervision: J.K. Approval of the final version of this work: all of
and do not necessarily reflect the views of the USAID or the NAS. the authors.

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14 Urol Int Jin/Park/Jung/Kim

DOI: 10.1159/000512880