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      Reply to Peng He, Xiaohui Wang, and Hao Li’s Letter to the Editor re: Yu Xiao, Kaiyu Qian, Yongwen Luo, et al. Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Renal Failure Patients: A Potential Covert Source of Infection. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.03.025

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          Abstract

          We appreciate the letter from He et al on our recent paper [1]. The authors provided strong clinical data in support of our primary findings. As He et al mentioned, chronic kidney disease (CKD) patients have a high rate of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in hemodialysis (HD) centers. Therefore, we once again call on medical providers to pay special attention to SARS-CoV-2 infection of dialysis patients. So far, no molecular mechanism has been identified to explain why the SARS-CoV-2 infection rate is higher among patients with CKD than in the normal population. We hypothesized that an immunosuppressive state could be linked to greater susceptibility to SARS-CoV-2. Therefore, organ transplant recipients and long-term users of immunosuppressive agents may be more susceptible to SARS-CoV-2 compared with the normal population. In 1971, a novel human polyomavirus, named BK polyomavirus (BKV), was identified from the urine of an immunosuppressed renal transplant recipient. Subsequent studies found that 80% of the normal population tested positive for anti-BKV antibodies without any symptoms. While nearly 10% of renal transplantation patients suffered from polyomavirus-associated nephropathy. Thereafter, it was generally accepted that intense immunosuppression might be a risk factor for BKV nephropathy [2]. Researchers in Italy recently reported that among 20 patients with COVID-19 who underwent transplantation, five died, four were admitted to the intensive care unit, and three were discharged; among 21 patients with COVID-19 undergoing HD, five died and four were discharged; and among five patients with CKD, two died and two were discharged [3]. The results indicate higher severity and mortality among these immunosuppressed patients. The authors point out that treatment can be divided into two phases. The first phase is associated with viral replication, for which antiviral drugs may be considered. The second phase involves lung and cytokine release syndromes, for which immunomodulatory drugs may be of benefit [3]. Furthermore, Zhu et al [4] enrolled ten renal transplant recipients with COVID-19 and ten of their family members diagnosed with COVID-19 pneumonia as a control group. They found that the transplant recipients had more severe disease and a longer virus shedding time than those in the control group. After a regimen involving cessation or reduction of immunosuppressive agents and administration of antiviral and supportive treatment, nine of the ten patients survived. The authors concluded that immunosuppression may have two opposing effects on the disease: making the early course of infection more severe and reducing mortality by suppressing the overactive immune response, in agreement with the opinions of Alberici et al. HD patients and renal transplant recipients are more vulnerable to SARS-CoV-2, possibly because of long-term immunosuppression, and are more likely to develop severe infection that may even be fatal. The treatment of COVID-19 in immunosuppressed patients may be more complicated than that in the normal population. More attention and special efforts are required to deal with the virus in this patient cohort. 

 Conflicts of interest: The authors have nothing to disclose. 

 Acknowledgments: We are grateful for a grant from the Medical Science Advancement Program of 10.13039/501100007046 Wuhan University (TFLC2018002).

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          Most cited references 1

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          BK polyomavirus in solid organ transplantation.

           P Randhawa,  Hans H. Hirsch,   (2013)
          The human BK polyomavirus (BKV) is the major cause of polyomavirus-associated nephropathy (PyVAN) putting 1-15% of kidney transplant patients at risk of premature allograft failure, but is less common in other solid organ transplants. Because effective antiviral therapies are lacking, screening kidney transplant patients for BKV replication in urine and blood has become the key recommendation to guide the reduction of immunosuppression in patients with BKV viremia. This intervention allows for expanding BKV-specific cellular immune responses, curtailing of BKV replication in the graft, and clearance of BKV viremia in 70-90% patients. Postintervention rejection episodes occur in 8-12%, most of which are corticosteroid responsive. Late diagnosis is faced with irreversible functional decline, poor treatment response, and graft loss. Adjunct therapies such as cidofovir, leflunomide and intravenous immunoglobulins have been used, but the benefit is not documented in trials. Retransplantation after PyVAN is largely successful, but requires close monitoring for recurrent BKV viremia. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
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            Author and article information

            Contributors
            Journal
            Eur Urol
            Eur. Urol
            European Urology
            Published by Elsevier B.V. on behalf of European Association of Urology.
            0302-2838
            1873-7560
            13 May 2020
            13 May 2020
            Affiliations
            [a ]Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
            [b ]Cancer Precision Diagnosis and Treatment and Translational Medicine, Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China
            Author notes
            [* ]Corresponding author. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. Tel.: +86 2767813104. wangxinghuan@ 123456whu.edu.cn
            Article
            S0302-2838(20)30348-1
            10.1016/j.eururo.2020.05.008
            7218393
            32405138
            © 2020 Published by Elsevier B.V. on behalf of European Association of Urology.

            Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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            Urology

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