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Vol. 66 No. 6: Issue 6

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Diagnostic and methodological evaluation of studies on the urinary shedding of SARS-CoV-2, compared to stool and serum: A systematic review and meta-analysis

https://doi.org/10.14715/cmb/2020.66.6.26
Mohammad Reza Roshandel
Urology Department of Icahn School of Medicine, Mount Sinai Hospitals, NY, USA
Masoud Nateqi
Center for Biotechnology and Genomics, Texas Tech University, Lubbock, TX, USA
Ramin Lak
Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran
Pooya Aavani
Department of Biology, Emory University, Atlanta, Georgia, USA
Reza Sari Motlagh
Urology Department of Medical University of Vienna, Austria
Shahrokh F. Shariat
Urology Department of Medical University of Vienna, Austria
Tannaz Aghaei Badr
Urology Department of Icahn School of Medicine, Mount Sinai Hospitals, NY, USA
John Sfakianos
Urology Department of Icahn School of Medicine, Mount Sinai Hospitals, NY, USA
Steven A Kaplan
Urology Department of Icahn School of Medicine, Mount Sinai Hospitals, NY, USA
Ashutosh K Tewari
Urology Department of Icahn School of Medicine, Mount Sinai Hospitals, NY, USA

Corresponding Author(s) : Ashutosh K Tewari

ashtewari@mountsinai.org

Cellular and Molecular Biology, Vol. 66 No. 6: Issue 6

Abstract

Investigating the infectivity of body fluid can be useful for preventative measures in the community and ensuring safety in the operating rooms and on the laboratory practices. We performed a literature search of clinical trials, cohorts, and case series using PubMed/MEDLINE, Google Scholar, and Cochrane library, and downloadable database of CDC. We excluded case reports and searched all-language articles for review and repeated until the final drafting. The search protocol was registered in the PROSPERO database. Thirty studies with urinary sampling for viral shedding were included. A total number of 1,271 patients were enrolled initially, among which 569 patients had undergone urinary testing. Nine studies observed urinary viral shedding in urine from 41 patients. The total incidence of urinary SARS-CoV-2 shedding was 8%, compared to 21.3% and 39.5 % for blood and stool, respectively. The summarized risk ratio (RR) estimates for urine positive rates compared to the pharyngeal rate was 0.08. The pertaining RR urine compared to blood and stool positive rates were 0.20 and 0.33, respectively. Our review concludes that not only the SARS-CoV-2 can be excreted in the urine in eight percent of patients but also its incidence may have associations with the severity of the systemic disease, ICU admission, and fatality rates. Moreover, the findings in our review suggest that a larger population size may reveal more positive urinary cases possibly by minimizing biases.

Keywords

SARS-CoV-2 COVID-19 Urine Real-time RT-PCR Infection.
Roshandel, M. R., Nateqi, M., Lak, R., Aavani, P., Sari Motlagh, R., F. Shariat, S., Aghaei Badr, T., Sfakianos, J., Kaplan, S. A., & Tewari, A. K. (2020). Diagnostic and methodological evaluation of studies on the urinary shedding of SARS-CoV-2, compared to stool and serum: A systematic review and meta-analysis. Cellular and Molecular Biology, 66(6), 148–156. https://doi.org/10.14715/cmb/2020.66.6.26
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References
  1. Delforge M-L, Costa E, Brancart F, Goldman D, Montesinos I, Zaytouni S, et al. Presence of Cytomegalovirus in urine and blood of pregnant women with primary infection might be associated with fetal infection. J Clin Virol. 2017;90:14-7.
  2. Niedrig M, Patel P, El Wahed AA, Schädler R, Yactayo S. Find the right sample: A study on the versatility of saliva and urine samples for the diagnosis of emerging viruses. BMC Infectious Diseases. 2018;18(1):707.
  3. Knutsson M, Kidd"Ljunggren K. Urine from chronic hepatitis B virus carriers: implications for infectivity. Journal of medical virology. 2000;60(1):17-20.
  4. Coronavirus disease 2019 (COVID-19): situation report, 131 [Internet]. World Health Organization. 2020 [cited 30 May 2020]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports.
  5. HUI DSC, WONG PC, Wang C. SARS: clinical features and diagnosis. Respirology. 2003;8:S20-S4.
  6. Rabaan AA, Al-Ahmed SH, Haque S, Sah R, Tiwari R, Malik YS, et al. SARS-CoV-2, SARS-CoV, and MERS-CoV: a comparative overview. Le Infezioni in Medicina. 2020;2:174-84.
  7. Zhang N, Gong Y, Meng F, Bi Y, Yang P, Wang F. Virus shedding patterns in nasopharyngeal and fecal specimens of COVID-19 patients. medRxiv. 2020.
  8. Ling Y, Xu S-B, Lin Y-X, Tian D, Zhu Z-Q, Dai F-H, et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chinese medical journal. 2020.
  9. Wang L, Li X, Chen H, Yan S, Li Y, Li D, et al. SARS-CoV-2 infection does not significantly cause acute renal injury: an analysis of 116 hospitalized patients with COVID-19 in a single hospital, Wuhan, China. Wuhan, China (2/17/2020). 2020.
  10. Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ (Clinical research ed). 2020;369:m1443.
  11. Tan W, Lu Y, Zhang J, Wang J, Dan Y, Tan Z, et al. Viral kinetics and antibody responses in patients with COVID-19. medRxiv. 2020.
  12. Peng L, Liu J, Xu W, Luo Q, Chen D, Lei Z, et al. SARS-CoV-2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens. Journal of Medical Virology.n/a(n/a).
  13. Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann H-W, et al. Randomized comparison of tenofovir disoproxil fumarate vs emtricitabine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology. 2014;146(4):980-8. e1.
  14. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nature Microbiology. 2020;5(4):562-9.
  15. Lo IL, Lio CF, Cheong HH, Lei CI, Cheong TH, Zhong X, et al. Evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical characteristics of 10 patients with COVID-19 in Macau. International Journal of Biological Sciences. 2020;16(10):1698.
  16. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet (London, England). 2020;395(10223):514-23.
  17. Mottrie A. ERUS (EAU Robotic Urology Section) guidelines during COVID-19 emergency. https://uroweb.org/wp-content/uploads/ERUS-guidelines-for-COVID-def.pdf: EAU; 2020.
  18. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. New England Journal of Medicine. 2020;382(16):1564-7.
  19. Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. Journal of Travel Medicine. 2020;27(2).
  20. Hasan S, Ahmad S, Masood R, Saeed S. Ebola virus: A global public health menace: A narrative review. Journal of Family Medicine and Primary Care. 2019;8(7):2189-201.
  21. Iwen PC, Smith PW, Hewlett AL, Kratochvil CJ, Lisco SJ, Sullivan JN, et al. Safety considerations in the laboratory testing of specimens suspected or known to contain Ebola virus. Oxford University Press Oxford, UK; 2015.
  22. Iwen PC, Stiles KL, Pentella MA. Safety considerations in the laboratory testing of specimens suspected or known to contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). American Journal of Clinical Pathology. 2020;153(5):567-70.
  23. Decaro N, Lorusso A. Novel human coronavirus (SARS-CoV-2): A lesson from animal coronaviruses. Vet Microbiol. 2020;244:108693.
  24. Lam SD, Bordin N, Waman VP, Scholes HM, Ashford P, Sen N, et al. SARS-CoV-2 spike protein predicted to form stable complexes with host receptor protein orthologues from mammals, but not fish, birds or reptiles. bioRxiv. 2020.
  25. Kariwa H, Fujiki M, Yoshimatsu K, Arikawa J, Takashima I, Hashimoto N. Urine-associated horizontal transmission of Seoul virus among rats. Archives of Virology. 1998;143(2):365-74.
  26. Li M, Wang B, Li L, Wong G, Liu Y, Ma J, et al. Rift Valley Fever Virus and Yellow Fever Virus in Urine: A Potential Source of Infection. Virologica Sinica. 2019;34(3):342-5.
  27. Ling Y, Xu SB, Lin YX, Tian D, Zhu ZQ, Dai FH, et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin Med J (Engl). 2020;133(9):1039-43.
  28. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gí¸tzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009;151(4):W65-94.
  29. Munn Z, Stern C, Aromataris E, Lockwood C, Jordan Z. What kind of systematic review should I conduct? A proposed typology and guidance for systematic reviewers in the medical and health sciences. BMC medical research methodology. 2018;18(1):5.
  30. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. International journal of evidence-based healthcare. 2015;13(3):147-53.
  31. Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, et al. Chapter 7: Systematic reviews of etiology and risk. Joanna Briggs Institute Reviewer's Manual The Joanna Briggs Institute. 2017:2019-05.
  32. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Annals of internal medicine. 2011;155(8):529-36.
  33. Zhang N, Gong Y, Meng F, Bi Y, Yang P, Wang F. Virus shedding patterns in nasopharyngeal and fecal specimens of COVID-19 patients. 2020:2020.03.28.20043059.
  34. Ling Y, Xu S-B, Lin Y-X, Tian D, Zhu Z-Q, Dai F-H, et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin Med J (Engl). 2020;133(9):1039-43.
  35. Wang L, Li X, Chen H, Yan S, Li D, Li Y, et al. Coronavirus Disease 19 Infection Does Not Result in Acute Kidney Injury: An Analysis of 116 Hospitalized Patients from Wuhan, China. American journal of nephrology. 2020;51(5):343-8.
  36. Tan W, Lu Y, Zhang J, Wang J, Dan Y, Tan Z, et al. Viral kinetics and antibody responses in patients with COVID-19. 2020.
  37. Mondanizadeh M, Rahimi E, Sarmadian H, Jamalian M, Khansarinejad B. Evaluation of SARS-CoV-2 existence in blood, urine, and rectal swab in positive patients with different virus titers. 2020.
  38. Peng L, Liu J, Xu W, Luo Q, Chen D, Lei Z, et al. SARS"CoV"2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens. 2020.
  39. Kujawski SA, Wong KK, Collins JP, Epstein L, Killerby ME, Midgley CM, et al. First 12 patients with coronavirus disease 2019 (COVID-19) in the United States. 2020.
  40. Ghinai I, McPherson TD, Hunter JC, Kirking HL, Christiansen D, Joshi K, et al. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. The Lancet. 2020;395(10230):1137-44.
  41. Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. 2020;323(15):1488-94.
  42. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. 2020;581(7809):465-9.
  43. Lescure F-X, Bouadma L, Nguyen D, Parisey M, Wicky P-H, Behillil S, et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. The Lancet Infectious Diseases. 2020;20(6):697-706.
  44. Yu F, Yan L, Wang N, Yang S, Wang L, Tang Y, et al. Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020;71(15):793-8.
  45. To KK-W, Tsang OT-Y, Leung W-S, Tam AR, Wu T-C, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. 2020.
  46. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. Jama. 2020;323(18):1843-4.
  47. Pan Y, Zhang D, Yang P, Poon LL, Wang QJTLID. Viral load of SARS-CoV-2 in clinical samples. 2020;20(4):411-2.
  48. Lo IL, Lio CF, Cheong HH, Lei CI, Cheong TH, Zhong X, et al. Evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical characteristics of 10 patients with COVID-19 in Macau. 2020;16(10):1698.
  49. Chan JF-W, Yip CC-Y, To KK-W, Tang TH-C, Wong SC-Y, Leung K-H, et al. Improved molecular diagnosis of COVID-19 by the novel, highly sensitive and specific COVID-19-RdRp/Hel real-time reverse transcription-PCR assay validated in vitro and with clinical specimens. 2020;58(5).
  50. Chen Y, Chen L, Deng Q, Zhang G, Wu K, Ni L, et al. The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients. 2020;92(7):833-40.
  51. Fang Z, Zhang Y, Hang C, Ai J, Li S, Zhang W. Comparisons of viral shedding time of SARS-CoV-2 of different samples in ICU and non-ICU patients. The Journal of infection. 2020;81(1):147-78.
  52. Mumm J-N, Osterman A, Ruzicka M, Stihl C, Vilsmaier T, Munker D, et al. Urinary Frequency as a Possibly Overlooked Symptom in COVID-19 Patients: Does SARS-CoV-2 Cause Viral Cystitis? European Urology. 2020.
  53. Diao B, Wen K, Chen J, Liu Y, Yuan Z, Han C, et al. Diagnosis of acute respiratory syndrome coronavirus 2 infection by detection of nucleocapsid protein. 2020.
  54. Qiu L, Liu X, Xiao M, Xie J, Cao W, Liu Z, et al. SARS-CoV-2 is not detectable in the vaginal fluid of women with severe COVID-19 infection. 2020.
  55. Xie C, Jiang L, Huang G, Pu H, Gong B, Lin H, et al. Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests. 2020.
  56. Kim JY, Ko JH, Kim Y, Kim YJ, Kim JM, Chung YS, et al. Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea. J Korean Med Sci. 2020;35(7):e86-e.
  57. Couturier A, Ferlicot S, Chevalier K, Guillet M, Essig M, Jauréguiberry S, et al. Indirect effects of severe acute respiratory syndrome coronavirus 2 on the kidney in coronavirus disease patients. Clinical kidney journal. 2020;13(3):347-53.
  58. Jeong HW, Kim SM, Kim HS, Kim YI, Kim JH, Cho JY, et al. Viable SARS-CoV-2 in various specimens from COVID-19 patients. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2020.
  59. Liu P, Cai J, Jia R, Xia S, Wang X, Cao L, et al. Dynamic surveillance of SARS-CoV-2 shedding and neutralizing antibody in children with COVID-19. 2020;9(1):1254-8.
  60. Kim JM, Kim HM, Lee EJ, Jo HJ, Yoon Y, Lee NJ, et al. Detection and Isolation of SARS-CoV-2 in Serum, Urine, and Stool Specimens of COVID-19 Patients from the Republic of Korea. Osong public health and research perspectives. 2020;11(3):112-7.
  61. Hung I, Cheng V, Wu A, Tang B, Chan K, Chu C, et al. Viral loads in clinical specimens and SARS manifestations. Emerging infectious diseases. 2004;10(9):1550.
  62. Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 2020;395(10223):514-23.
  63. Fang Z, Zhang Y, Hang C, Zhang W, Ai J, Li S. Comparisons of nucleic acid conversion time of SARS-CoV-2 of different samples in ICU and non-ICU patients. The Journal of infection. 2020.
  64. Kujawski SA, Wong KK, Collins JP, Epstein L, Killerby ME, Midgley CM, et al. First 12 patients with coronavirus disease 2019 (COVID-19) in the United States. MedRxiv. 2020.
  65. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020:1-5.
  66. Chan PK, To W-K, Ng K-C, Lam RK, Ng T-K, Chan RC, et al. Laboratory diagnosis of SARS. Emerging infectious diseases. 2004;10(5):825.
  67. Xu D, Zhang Z, Jin L, Chu F, Mao Y, Wang H, et al. Persistent shedding of viable SARS-CoV in urine and stool of SARS patients during the convalescent phase. Eur J Clin Microbiol Infect Dis. 2005;24(3):165-71.
  68. Wang L, Li X, Chen H, Yan S, Li Y, Li D, et al. SARS-CoV-2 infection does not significantly cause acute renal injury: an analysis of 116 hospitalized patients with COVID-19 in a single hospital, Wuhan, China. 2020.
  69. Yu F, Yan L, Wang N, Yang S, Wang L, Tang Y, et al. Quantitative detection and viral load analysis of SARS-CoV-2 in infected patients. Clinical Infectious Diseases. 2020.
  70. Pan Y, Zhang D, Yang P, Poon LL, Wang Q. Viral load of SARS-CoV-2 in clinical samples. The Lancet infectious diseases. 2020;20(4):411-2.
  71. Cheung KS, Hung IF, Chan PP, Lung K, Tso E, Liu R, et al. 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. 2020.
  72. Chan JF, Yip CC, To KK, Tang TH, Wong SC, Leung KH, et al. Improved Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro and with Clinical Specimens. J Clin Microbiol. 2020;58(5).
  73. Overbergh L, Giulietti A, Valckx D, Decallonne R, Bouillon R, Mathieu C. The use of real-time reverse transcriptase PCR for the quantification of cytokine gene expression. J Biomol Tech. 2003;14(1):33-43.
  74. Winichakoon P, Chaiwarith R, Liwsrisakun C, Salee P, Goonna A, Limsukon A, et al. Negative nasopharyngeal and oropharyngeal swabs do not rule out COVID-19. Journal of clinical microbiology. 2020;58(5).
  75. Wu J, Liu J, Zhao X, Liu C, Wang W, Wang D, et al. Clinical Characteristics of Imported Cases of Coronavirus Disease 2019 (COVID-19) in Jiangsu Province: A Multicenter Descriptive Study. Clinical Infectious Diseases. 2020.
  76. Parshionikar S, Laseke I, Fout GS. Use of propidium monoazide in reverse transcriptase PCR to distinguish between infectious and noninfectious enteric viruses in water samples. Appl Environ Microbiol. 2010;76(13):4318-26.
  77. Cheng VC, Lau SK, Woo PC, Yuen KY. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev. 2007;20(4):660-94.
  78. Bharucha T, Sengvilaipaseuth O, Seephonelee M, Vongsouvath M, Vongsouvath M, Rattanavong S, et al. Viral RNA Degradation Makes Urine a Challenging Specimen for Detection of Japanese Encephalitis Virus in Patients With Suspected CNS Infection. Open Forum Infect Dis. 2019;6(3):ofz048-ofz.
  79. Janvier F, Delaune D, Poyot T, Valade E, Merens A, Rollin PE, et al. Ebola virus RNA stability in human blood and urine in West Africa's environmental conditions. Emerging Infectious Diseases. 2016;22:292+.
  80. Niedrig M, Patel P, Abd El Wahed A, Schädler R, Yactayo S. Find the right sample: A study on the versatility of saliva and urine samples for the diagnosis of emerging viruses. BMC infectious diseases. 2018;18(1):1-14.
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Author Biographies

John Sfakianos, Urology Department of Icahn School of Medicine, Mount Sinai Hospitals, NY, USA
Urology department
Steven A Kaplan, Urology Department of Icahn School of Medicine, Mount Sinai Hospitals, NY, USA
Urology department
Ashutosh K Tewari, Urology Department of Icahn School of Medicine, Mount Sinai Hospitals, NY, USA
Urology department
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