A systematic review on COVID-19: urological manifestations, viral RNA detection and special considerations in urological conditions

Abstract

Purpose and objective

We performed a systematic review on COVID-19 and its potential urological manifestations.

Methods

A literature search was performed using combination of keywords (MeSH terms and free text words) relating to COVID-19, urology, faeces and stool on multiple databases. Primary outcomes were the urological manifestations of COVID-19, and SARS-CoV-2 viral RNA detection in urine and stool samples. Meta-analyses were performed when there were two or more studies reporting on the same outcome. Special considerations in urological conditions that were relevant in the pandemic of COVID-19 were reported in a narrative manner.

Results

There were a total of 21 studies with 3714 COVID-19 patients, and urinary symptoms were absent in all of them. In patients with COVID-19, 7.58% (95% CI 3.30–13.54%) developed acute kidney injury with a mortality rate of 93.27% (95% CI 81.46–100%) amongst them. 5.74% (95% CI 2.88–9.44%) of COVID-19 patients had positive viral RNA in urine samples, but the duration of viral shedding in urine was unknown. 65.82% (95% CI 45.71–83.51%) of COVID-19 patients had positive viral RNA in stool samples, which were detected from 2 to 47 days from symptom onset. 31.6% of renal transplant recipients with COVID-19 required non-invasive ventilation, and the overall mortality rate was 15.4%.

Conclusions

Acute kidney injury leading to mortality is common amongst COVID-19 patients, likely as a result of direct viral toxicity. Viral RNA positivity was detected in both urine and stool samples, so precautions are needed when we perform transurethral or transrectal procedures.

Introduction

As cases of Coronavirus Disease 2019 (COVID-19) reaches the 1.7 million mark, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused over 100,000 deaths worldwide. Typical symptoms of COVID-19 include fever, cough, sore throat, fatigue, sputum production, shortness of breath and headache [1]. However, recent studies showed that COVID-19 could have other non-respiratory manifestations [2, 3]. As urologists, we manage patients with urological symptoms, and we perform both transurethral and transrectal procedures in our clinical practices. It is possible that we might encounter COVID-19 patients in our urological practices. To protect ourselves, our colleagues and our patients, it is important to understand thoroughly about the urological manifestations of COVID-19, and the possible routes of viral transmission via urine and stool. It is also important to understand whether there are any special considerations in managing specific urological conditions under the circumstances of COVID-19. Therefore, we performed a systematic review to summarize the clinical manifestations, viral RNA detection and special considerations of COVID-19 from an urologist’s perspective.

Material and methods

We systematically reviewed the literature on COVID-19 and its relevance to our urological practice. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [4].

Literature search

A comprehensive literature search was performed using combination of keywords (MeSH terms and free text words) including ‘COVID-19’/‘SARS-CoV-2’, ‘Urology’/‘Urogenital System’, and “Stool”/“Faeces”. MEDLINE, EMBASE and Cochrane library (CENTRAL and CDSR) were searched up to 8th April 2020. A limit of after 2019 was imposed since COVID-19 was first reported in late 2019. The search strategy was presented in Online Appendix 1. Additional articles were sought from the reference lists of the included studies.

Selection criteria

All articles identified from the literature search were screened by two independent reviewers (J.Y.C.T. and V.W.S.C.). We included studies on COVID-19 in adult patients. Case reports, case series, observational studies, non-randomized studies and randomised trials that were published in English were included in this review. Conferences abstracts, letters to editors, commentaries and editorials were also included. Studies related to obstetrics and gynaecology were excluded. Studies on severe acute respiratory syndrome (SARS) and Middles East respiratory syndrome (MERS) but not COVID-19 were excluded.

Data collection

For eligible studies, study information including first authors, site of study, inclusion and exclusion criteria, sample size, age and sex were recorded. A standardised form for data entry has been devised to focus on the following areas: (1) urological manifestations of COVID-19; (2) detection of viral RNA in urine and stool samples; (3) special considerations in urological conditions.

Data synthesis and statistical analysis

Primary outcomes of our study included urological manifestations of COVID-19, detection rates of SARS-CoV-2 viral RNA in urine and stool samples, and special considerations in urological conditions. For the urological manifestations and viral RNA detection rates, data were pool analysed using MetaXL and Microsoft Excel when there are two or more studies with at least four patients reporting the same outcome under the same definition. Random effects model was used. Double arcsine transformation was used to pool the proportions. The results were presented by forest plots, illustrating the prevalences, 95% confidence intervals and weightings. Cochran’s Q test was used to detect heterogeneity, and a p value of < 0.10 indicates significant heterogeneity. I2 statistics was calculated to measure the proportion of total variation in study estimates attributed to heterogeneity with I2 > 50% suggests substantial heterogeneity. Special considerations in urological conditions that were relevant in the pandemic of COVID-19 were reported in a narrative manner.

Results

The PRISMA flow diagram was shown in Fig. 1. A total of 303 records were identified upon literature search, and 34 additional records were sought from reference lists of the included literature. 258 records remained after removing duplicates. Among them, 154 were excluded upon initial screening, and 15 studies were excluded upon full-text review. Overall, 89 records were included in the qualitative synthesis and 25 studies were included in the quantitative synthesis. Table 1 summarised the study characteristics of the 25 studies [1, 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28] that were included in the quantitative analysis.

Fig. 1
figure1

PRISMA flow diagram

Table 1 Baseline characteristics of the studies included in the meta-analysis

Urological manifestations of COVID-19

There were a total of 21 studies reporting urinary symptoms and/or gastrointestinal symptoms, with a total of 3714 COVID-19 patients being included. Urinary symptoms were absent in all 3714 patients. Sighinolfi et al. briefly mentioned his encounter of two patients with indwelling urological devices (ureteral stent or nephrostomy tube), who had fever ‘attributed’ to urinary infection, but eventually turned out to be COVID-19 [29]. Yang et al. [23] reported one COVID-19 patient who suffered from urinary tract infection due to candida albicans during hospitalisation. To sum up, urinary symptoms is not a presenting symptom of COVID-19, but it can be a concomitant symptom due to other urological conditions.

Acute kidney injury (AKI) can be a manifestation of COVID-19 patients. Our meta-analysis included 12 studies and 3266 patients, and the pooled prevalence of AKI was 7.58% (95% CI 3.30–13.54%) (Fig. 2a). Amongst the 65 patients with AKI in three studies, the pooled mortality rate was 93.27% (95% CI 81.46–100%) (Fig. 2b). A cohort study by Cheng et al. also established associations between stage 1, 2 and 3 AKI, and in-hospital death, with hazard ratios of 1.90 (95% CI 0.76–4.75), 3.53 (95% CI 1.50–8.27) and 4.72 (95% CI 2.55–8.75) respectively [7]. Regarding the underlying pathophysiological mechanism, a recent molecular modelling study revealed that COVID-19 had a strong interaction with angiotensin converting enzyme 2 (ACE2) [30], and ACE2 had been shown to be a major receptor involved in the entry of COVID-19 into human cells [31]. Besides type II alveolar cells, proximal tubular cells of kidney also had abundant expression of ACE2 receptor [31,32,33]. Hence, the virus might be able to spread to the kidneys via the blood stream [34]. ACE2 were also expressed in other organs including testis and bladder [30, 31, 33], therefore it was postulated that these organs might be at risk of damage upon COVID-19. However, up to date, there were no reported cases of testicular or bladder manifestations following COVID-19 infection.

Fig. 2
figure2

a Pooled prevalence of acute kidney injury, and b pooled mortality rate in patients with acute kidney injury

Detection of viral RNA in urine and stool samples

There were a total of 11 studies that reported the number of patients who had their urine tested for SARS-CoV-2 viral RNA. Amongst the studies, 195 patients were included and the pooled rate of RNA positivity was 5.74% (95% CI 2.88–9.44%) (Fig. 3a). It was difficult to determine the duration of viral shedding due to the relatively low rate of RNA positivity and the lack of serial testing [13, 15, 17]. Peng et al. reported positive urine sample for a patient on the 7th day of symptom onset. Ling et al. reported three out of four cases where urine samples remained positive even after throat swabs had converted negative, but the viral RNA conversion time was not precisely reported (at least 6 days from symptom onset) [13]. The duration of viral shedding in urine samples remained largely unknown.

Fig. 3
figure3

a Pooled rate of urine RNA positivity, and b pooled rate of stool RNA positivity

Our meta-analysis included 12 studies that reported the number of patients with stools tested for SARS-CoV-2 viral RNA. Amongst the studies, 325 were included and the pooled rate of RNA positivity was 65.82% (95% CI 45.71–83.51%) (Fig. 3b). Due to a lack of a standardised serial testing protocol in the included studies, it is difficult to calculate the duration of viral shedding. However, positive viral RNA in stool could be detected as early as 2 days from symptom onset, [10, 14] and could be persistent up to day 47 from symptom onset despite a negative throat swab [21]. In a case series by Ling et al. 78.2% of the patients with positive stool samples were still positive after throat swabs had converted negative with a median delay of 2 days [13]. In the same study, the median days for RNA conversion in stool samples was 11 days, but it could be up to 20 days in patients who were on steroids.

Special considerations in managing specific urological conditions

Renal transplant recipients and COVID-19

There were six studies [35,36,37,38,39,40] reporting a total of 19 cases COVID-19 in renal transplant recipients (Table 2). The mean age was 47.4 ± 13.3 years. 21.1% of the patients were female. The majority of the patients had fever (94.7%) and cough (94.7%), and diarrhoea was present in 16.7% of them. 73.7% of the renal transplant recipients had elevated serum creatinine, and 31.6% required non-invasive ventilation. By the time of reporting, six patients were still under treatment in hospital. In the remaining 13 patients, 11 of them recovered (84.6%) and the remaining two patients died (15.4%). The proportion of patients requiring non-invasive ventilation and the mortality rate appeared to higher than the general population [1].

Table 2 Baseline characteristics of the studies included in the meta-analysis

Urolithiasis and COVID-19

There were no reports on possible associations between COVID-19 and urolithiasis. However, non-steroidal anti-inflammatory drugs (NSAIDS), a medication commonly used to alleviate stone-related colicky pain has raised concerns in the community. Fang et al. [41] reported that upregulation of ACE2 might increase the risk of developing severe and fatal COVID-19. NSAIDS also increases ACE2 and there is a worry that it might induce similar effect [41]. US Food and Drug Administration recently announced that there was not enough scientific evidence connecting the use of NSAIDs, such as ibuprofen, with worsening COVID-19 symptoms [42]. Therefore, the use of NSAIDs in renal colic management should still follow established indications.

Although urolithiasis is a non-malignant condition, stones can be obstructing and may lead to renal function deterioration if definitive surgery was delayed in the pandemic of COVID-19. Proletti et al. made recommendations on the priority of stone surgeries mainly based on patient and stone factors [43]. These recommendations will be useful in prioritising stone surgeries especially if the COVID-19 situation worsens with time.

Urological cancers and COVID-19

There were no reports demonstrating a definite association between COVID-19 and urological cancers. Interestingly, Liang et al. [44] reported a cohort of 1590 COVID-19 positive patients; it was noted that 18 cases (1%) had a history of cancer, which appeared to be of a higher incidence than the overall Chinese population (0.29%). Furthermore, cancer patients were found to have a higher risk of requiring invasive ventilation or death (39% in cancer patients vs 8% in non-cancer patients, p = 0.0003). However, among the 18 patients, only one patient had history of urological cancer (bladder cancer). The results were at most hypothesis generating and more data would be needed on this aspect.

In the pandemic of COVID-19, there has been increasing demand for ventilator-level care and we might need to consider triaging urological surgeries. Stensland et al. made recommendations on the priority of surgeries based on its potential impact on patient survival, and suggested alternatives that may spare the use of ventilators [45]. Such recommendations will be extremely helpful when prioritisation of surgeries is deemed necessary.

Discussion

The increasing number of COVID-19 cases has raised significant fear among healthcare professionals and the general population globally. While COVID-19 primarily affects the respiratory system, it is possible for the disease to have non-respiratory manifestations. It is extremely important for urologists to learn about the potential implications of COVID-19 on their clinical practices.

Our study showed that COVID-19 was unlikely to cause any urinary symptoms, so the presence of urinary symptoms alone should not raise any significant concerns of COVID-19. On the other hand, if the patient has additional symptoms such as fever on top of urinary symptoms, we cannot assume that the fever is attributed to an underlying urological cause and we must maintain a high level of suspicion for possible COVID-19 [29].

There have been suggestions on the use of procalcitonin to differentiate between COVID-19 and urological conditions presenting with fever. Procalcitonin levels are likely to rise in bacterial, parasitic and fungal infections but not viral infections [7, 29, 38]. Procalcitonin may serve as a marker to preliminarily differentiate between COVID-19 and urological infections [46]. On the other hand, rapid tests for detecting SARS-CoV-2 will be of utmost importance in case of any suspicion of COVID-19.

Our study showed that the prevalence of AKI in COVID-19 patients was 7.58%. AKI is a possible manifestation of COVID-19, and its occurrence usually indicates a severe disease with high mortality rate. The association of COVID-19 and AKI was believed to be related to ACE receptors [11, 30, 47]. As ACE receptors were also found in testis and bladder, it was postulated that COVID-19 might have manifestations in these organs [31, 33]. However, this is largely theoretical without any actual cases being reported. Further studies will be needed to determine whether such postulation is a genuine concern. Although concerns of acute kidney injury as an indirect effect of sepsis and multiorgan failure has been reported, Diao et al. has reported direct cytotoxicity of SARS-CoV-2 against kidney tubules as a result of a direct infection, initiation of CD68+ macrophage and complement C5b-9 deposition [48].

Our study showed that 5.74% of the COVID-19 patients had positive viral RNA in urine samples. However, none of the patients had urinary symptoms, so it would be difficult for us to determine the necessity of viral RNA testing without the presence of other symptoms (such as fever, respiratory and gastrointestinal symptoms). Currently, there is also insufficient data regarding the duration of viral shedding in urine. Further studies to investigate the duration of viral shedding in urine are needed to inform future clinical practice.

Our results also showed that viral shedding in stool could be persistent up to 6 weeks after symptom onset. We should incorporate this information when we manage suspected, active and recovering COVID-19 patients, and decide when it is safe to perform transrectal procedures when it is clinically indicated. When the transrectal procedure is considered mandatory in an urgent manner, the use of protective personal equipment must be ensured to protect healthcare workers from being infected.

To our knowledge, this is the first systematic review investigating COVID-19 with relevance to urology. In this study, the implications of COVID-19 on an urologist’s daily practice has been comprehensively covered. However, there are several limitations in our study. First, COVID-19 has only started five months ago, and there is a lack of high-quality evidence in this area. Second, urological symptoms might be under-reported and urine viral RNA might be under-tested. Third, most of the studies included in this systematic review were based in China. The implications of COVID-19 may be different in other areas like Europe and America, where the pandemic is most severe now. Nevertheless, we believe that COVID-19 is a rapidly evolving crisis that warrants a timely systematic review and we hope the information will be useful for urologists in their clinical practices.

Conclusions

Our systematic review showed that urinary symptom is not a clinical manifestation of COVID-19. Acute kidney injury could occur in COVID-19 patients, and its occurrence was associated with high mortality rate. As viral RNA positivity was detected in both urine and stool samples, precautions are needed when urologists perform transurethral or transrectal procedures. Special considerations in managing specific urological conditions are also needed in the pandemic of COVID-19.

References

  1. 1.

    Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, Liu L, Shan H, Lei C-l, Hui DSC, Du B, Li L-j, Zeng G, Yuen K-Y, Chen R-c, Tang C-l, Wang T, Chen P-y, Xiang J, Li S-y, Wang J-l, Liang Z-j, Peng Y-x, Wei L, Liu Y, Hu Y-h, Peng P, Wang J-m, Liu J-y, Chen Z, Li G, Zheng Z-j, Qiu S-q, Luo J, Ye C-j, Zhu S-y, Zhong N-s (2020) Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. https://doi.org/10.1056/NEJMoa2002032

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Wong SH, Lui RN, Sung JJ (2020) Covid-19 and the digestive system. J Gastroenterol Hepatol. https://doi.org/10.1111/jgh.15047

    Article  PubMed  Google Scholar 

  3. 3.

    Cheung KS, Hung IFN, Chan PPY, Lung KC, Tso E, Liu R, Ng YY, Chu MY, Chung TWH, Tam AR, Yip CCY, Leung K-H, Yim-Fong Fung A, Zhang RR, Lin Y, Cheng HM, Zhang AJX, To KKW, Chan K-H, Yuen K-Y, Leung WK (2020) Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from the Hong Kong cohort and systematic review and meta-analysis. Gastroenterology. https://doi.org/10.1053/j.gastro.2020.03.065

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535. https://doi.org/10.1136/bmj.b2535

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Chen Y, Chen L, Deng Q, Zhang G, Wu K, Ni L, Yang Y, Liu B, Wang W, Wei C, Yang J, Ye G, Cheng Z (2020) The presence of SARS-CoV-2 RNA in feces of COVID-19 patients. J Med Virol. https://doi.org/10.1002/jmv.25825

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, Wang T, Guo W, Chen J, Ding C, Zhang X, Huang J, Han M, Li S, Luo X, Zhao J, Ning Q (2020) Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 368:m1091. https://doi.org/10.1136/bmj.m1091

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G (2020) Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. https://doi.org/10.1016/j.kint.2020.03.005

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Deng Y, Liu W, Liu K, Fang YY, Shang J, Zhou L, Wang K, Leng F, Wei S, Chen L, Liu HG (2020) Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study. Chin Med J (Engl). https://doi.org/10.1097/cm9.0000000000000824

    Article  PubMed Central  Google Scholar 

  9. 9.

    Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Lescure F-X, Bouadma L, Nguyen D, Parisey M, Wicky P-H, Behillil S, Gaymard A, Bouscambert-Duchamp M, Donati F, Le Hingrat Q, Enouf V, Houhou-Fidouh N, Valette M, Mailles A, Lucet J-C, Mentre F, Duval X, Descamps D, Malvy D, Timsit J-F, Lina B, der Werf S, Yazdanpanah Y (2020) Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis. https://doi.org/10.1016/S1473-3099(20)30200-0

    Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Li Z, Wu M, Yao J, Guo J, Liao X, Song S, Li J, Duan G, Zhou Y, Wu X, Zhou Z, Wang T, Hu M, Chen X, Fu Y, Lei C, Dong H, Xu C, Hu Y, Han M, Zhou Y, Jia H, Chen X, Yan J (2020) Caution on kidney dysfunctions of COVID-19 patients. MedRxiv. https://doi.org/10.1101/2020.02.08.20021212

    Article  Google Scholar 

  12. 12.

    Lin L, Jiang X, Zhang Z, Huang S, Zhang Z, Fang Z, Gu Z, Gao L, Shi H, Mai L, Liu Y, Lin X, Lai R, Yan Z, Li X, Shan H (2020) Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. https://doi.org/10.1136/gutjnl-2020-321013

    Article  PubMed  Google Scholar 

  13. 13.

    Ling Y, Xu SB, Lin YX, Tian D, Zhu ZQ, Dai FH, Wu F, Song ZG, Huang W, Chen J, Hu BJ, Wang S, Mao EQ, Zhu L, Zhang WH, Lu HZ (2020) Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin Med J (Engl). https://doi.org/10.1097/cm9.0000000000000774

    Article  Google Scholar 

  14. 14.

    Lo IL, Lio CF, Cheong HH, Lei CI, Cheong TH, Zhong X, Tian Y, Sin NN (2020) Evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical characteristics of 10 patients with COVID-19 in Macau. Int J Biol Sci 16(10):1698–1707. https://doi.org/10.7150/ijbs.45357

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Peng L, Liu J, Xu W, Luo Q, Deng K, Lin B, Gao Z (2020) 2019 Novel Coronavirus can be detected in urine, blood, anal swabs and oropharyngeal swabs samples. medRxiv. https://doi.org/10.1101/2020.02.21.20026179

    Article  Google Scholar 

  16. 16.

    Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, Gong W, Liu X, Liang J, Zhao Q, Huang H, Yang B, Huang C (2020) Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2020.0950

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Wang L, Li X, Chen H, Yan S, Li D, Li Y, Gong Z (2020) Coronavirus disease 19 infection does not result in acute kidney injury: an analysis of 116 hospitalized patients from Wuhan, China. Am J Nephrol. https://doi.org/10.1159/000507471

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. https://doi.org/10.1001/jama.2020.1585

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan W (2020) Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. https://doi.org/10.1001/jama.2020.3786

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, Niemeyer D, Jones TC, Vollmar P, Rothe C, Hoelscher M, Bleicker T, Brünink S, Schneider J, Ehmann R, Zwirglmaier K, Drosten C, Wendtner C (2020) Virological assessment of hospitalized patients with COVID-2019. Nature. https://doi.org/10.1038/s41586-020-2196-x

    Article  PubMed  Google Scholar 

  21. 21.

    Wu Y, Guo C, Tang L, Hong Z, Zhou J, Dong X, Yin H, Xiao Q, Tang Y, Qu X, Kuang L, Fang X, Mishra N, Lu J, Shan H, Jiang G, Huang X (2020) Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. Lancet Gastroenterol Hepatol. https://doi.org/10.1016/S2468-1253(20)30083-2

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Xie C, Jiang L, Huang G, Pu H, Gong B, Lin H, Ma S, Chen X, Long B, Si G, Yu H, Jiang L, Yang X, Shi Y, Yang Z (2020) Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests. Int J Infect Dis 93:264–267. https://doi.org/10.1016/j.ijid.2020.02.050

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Yang X, Yu Y, Xu J, Shu H, Ja X, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y (2020) Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. https://doi.org/10.1016/S2213-2600(20)30079-5

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng O-T, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MI-C, Chan M, Vasoo S, Wang L-F, Tan BH, Lin RTP, Lee VJM, Leo Y-S, Lye DC, Team ftSNCOR (2020) Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. https://doi.org/10.1001/jama.2020.3204

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Yu F, Yan L, Wang N, Yang S, Wang L, Tang Y, Gao G, Wang S, Ma C, Xie R, Wang F, Tan C, Zhu L, Guo Y, Zhang F (2020) Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients. Clin Infect Dis. https://doi.org/10.1093/cid/ciaa345

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Zhang B, Zhou X, Qiu Y, Feng F, Feng J, Jia Y, Zhu H, Hu K, Liu J, Liu Z, Wang S, Gong Y, Zhou C, Zhu T, Cheng Y, Liu Z, Deng H, Tao F, Ren Y, Cheng B, Gao L, Wu X, Yu L, Huang Z, Mao Z, Song Q, Zhu B, Wang J (2020) Clinical characteristics of 82 death cases with COVID-19. medRxiv. https://doi.org/10.1101/2020.02.26.20028191

    Article  Google Scholar 

  27. 27.

    Zhang W, Du R-H, Li B, Zheng X-S, Yang X-L, Hu B, Wang Y-Y, Xiao G-F, Yan B, Shi Z-L, Zhou P (2020) Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect 9(1):386–389. https://doi.org/10.1080/22221751.2020.1729071

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Zhang J, Wang S, Xue Y (2020) Fecal specimen diagnosis 2019 novel coronavirus-infected pneumonia. J Med Virol. https://doi.org/10.1002/jmv.25742

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Sighinolfi MC, Rocco B, Mussini C (2020) COVID-19: Importance of the awareness of the clinical syndrome by urologists. Eur Urol S0302–2838(20):30204–30209. https://doi.org/10.1016/j.eururo.2020.0

    Article  Google Scholar 

  30. 30.

    Chen Y, Guo Y, Pan Y, Zhao ZJ (2020) Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2020.02.071

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Fan C, Li K, Ding Y, Lu WL, Wang J (2020) ACE2 Expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. medRxiv. https://doi.org/10.1101/2020.02.12.20022418

    Article  Google Scholar 

  32. 32.

    Qi F, Qian S, Zhang S, Zhang Z (2020) Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2020.03.044

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Zou X, Chen K, Zou J, Han P, Hao J, Han Z (2020) Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. https://doi.org/10.1007/s11684-020-0754-0

    Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Pan X-w, Xu D, Zhang H, Zhou W, Wang L-h, Cui X-g (2020) Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Med. https://doi.org/10.1007/s00134-020-06026-1

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Guillen E, Pineiro GJ, Revuelta I, Rodriguez D, Bodro M, Moreno A, Campistol JM, Diekmann F, Ventura-Aguiar P (2020) Case report of COVID-19 in a kidney transplant recipient: does immunosuppression alter the clinical presentation? Am J Transplant. https://doi.org/10.1111/ajt.15874

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Zhu L, Xu X, Ma K, Yang J, Guan H, Chen S, Chen Z, Chen G (2020) Successful recovery of COVID-19 pneumonia in a renal transplant recipient with long-term immunosuppression. Am J Transplant. https://doi.org/10.1111/ajt.15869

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Gandolfini I, Delsante M, Fiaccadori E, Zaza G, Manenti L, Degli Antoni A, Peruzzi L, Riella LV, Cravedi P, Maggiore U (2020) COVID-19 in kidney transplant recipients. Am J Transplant. https://doi.org/10.1111/ajt.15891

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Zhu L, Gong N, Liu B, Lu X, Chen D, Chen S, Shu H, Ma K, Xu X, Guo Z, Lu E, Chen D, Ge Q, Cai J, Jiang J, Wei L, Zhang W, Chen G, Chen Z (2020) Coronavirus disease 2019 pneumonia in immunosuppressed renal transplant recipients: a summary of 10 confirmed cases in Wuhan. China. Eur Urol. 77(6):748–54. https://doi.org/10.1016/j.eururo.2020.03.039

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Zhang H, Chen Y, Yuan Q, Xia Q-X, Zeng X-P, Peng J-T, Liu J, Xiao X-Y, Jiang G-S, Xiao H-Y, Xie L-B, Chen J, Liu J-L, Xiao X, Su H, Zhang C, Zhang X-P, Yang H, Li H, Wang Z-D (2020) Identification of kidney transplant recipients with coronavirus disease 2019. Eur Urol. https://doi.org/10.1016/j.eururo.2020.03.030

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Wang J, Li X, Cao G, Wu X, Wang Z, Yan T (2020) COVID-19 in a kidney transplant patient. Eur Urol. https://doi.org/10.1016/j.eururo.2020.03.036

    Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Fang L, Karakiulakis G, Roth M (2020) Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 8(4):e21. https://doi.org/10.1016/S2213-2600(20)30116-8

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    (2020) FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19. Accessed 5 April 2020

  43. 43.

    Proietti S, Gaboardi F, Giusti G (2020) Endourological stone management in the era of the COVID-19. Eur Urol. S0302–2838(20)30217: https://doi.org/10.1016/j.eururo.2020.03.042

    CAS  Article  Google Scholar 

  44. 44.

    Liang W, Guan W, Chen R, Wang W, Li J, Xu K, Li C, Ai Q, Lu W, Liang H, Li S, He J (2020) Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol 21(3):335–337. https://doi.org/10.1016/s1470-2045(20)30096-6

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Stensland KD, Morgan TM, Moinzadeh A et al (2020) Considerations in the triage of urologic surgeries during the COVID-19 pandemic. Eur Urol S0302–2838(20):30202–30205. https://doi.org/10.1016/j.eururo.2020.03.027

    CAS  Article  Google Scholar 

  46. 46.

    Sugimoto K, Adomi S, Koike H, Esa A (2013) Procalcitonin as an indicator of urosepsis. Res Rep Urol 5:77–80. https://doi.org/10.2147/RRU.S42711

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    South AM, Diz D, Chappell MC (2020) COVID-19, ACE2 and the cardiovascular consequences. Am J Physiol Heart Circ Physiol. https://doi.org/10.1152/ajpheart.00217.2020

    Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Diao B, Wang C, Wang R, Feng Z, Tan Y, Wang H, Wang C, Liu L, Liu Y, Liu Y, Wang G, Yuan Z, Ren L, Wu Y, Chen Y (2020) Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. medRxiv. https://doi.org/10.1101/2020.03.04.20031120

    Article  Google Scholar 

Download references

Funding

No funding or other financial support was received.

Author information

Affiliations

Authors

Contributions

VWSC: project development, data collection, data analysis, manuscript writing. PKFC: data analysis, manuscript writing. CHY: data analysis, manuscript writing. CYY: data collection, data analysis. CFN: data analysis, manuscript writing. JYTT: project development, data collection, data analysis, manuscript writing/editing.

Corresponding author

Correspondence to Jeremy Yuen-Chun Teoh.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals/ ethics approval

Not applicable.

Informed consent to participate

Not applicable.

Informed consent for publication

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

345_2020_3246_MOESM1_ESM.docx

Supplementary material 1 (DOCX 24 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chan, VS., Chiu, P.KF., Yee, CH. et al. A systematic review on COVID-19: urological manifestations, viral RNA detection and special considerations in urological conditions. World J Urol (2020). https://doi.org/10.1007/s00345-020-03246-4

Download citation

Keywords

  • COVID-19
  • SARS-CoV-2
  • Viral RNA
  • Urine
  • Stool
  • Urology
  • Acute kidney injury