<?xml version="1.1" encoding="utf-8"?>
<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">UR</journal-id><journal-title-group><journal-title>Urology Research</journal-title></journal-title-group><issn>3083-4910</issn><eissn>2981-8230</eissn><publisher><publisher-name>Bio-Byword Scientific Publishing Pty. Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.26689/ur.v2i3.8513</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Clinical Features and Risk Factors of COVID-19-Associated Fungal Infections in Kidney Transplant Recipients</title><url>https://artdesignp.com/journal/UR/2/3/10.26689/ur.v2i3.8513</url><author>SunChonghao,DongHao,TanHaotian,ShenCongrong,DingZhenshan,ZhaoYing,WangJianfeng</author><pub-date pub-type="publication-year"><year>2024</year></pub-date><volume>2</volume><issue>3</issue><history><date date-type="pub"><published-time>2024-10-15</published-time></date></history><abstract>Objective: To investigate the clinical features, outcomes, and risk factors of fungal infections in kidney transplant recipients (KTRs) as a result of coronavirus disease 2019 (COVID-19). Methods: We retrospectively analyzed 54 KTRs with COVID-19 who were hospitalized at the China-Japan Friendship Hospital from December 1, 2022, to April 1, 2023. With a mean age of 50 ± 12 years, there were 43 men and 11 women participated. For KTRs with COVID-19, we employed multivariate logistic regression analysis to identify the risk factors. Results: Twenty (37.0%) patients in this study had fungal infections as a result of COVID-19. Patients with fungal infections had significantly higher rates of mortality (50.0%, 10/20 vs. 2.9%, 1/34, P &amp;lt; 0.001), acute respiratory distress syndrome (ARDS) (65.0%, 13/20 vs. 26.5%, 9/34, P = 0.005), and acute kidney injury (AKI) (60%, 12/20 vs. 23.5%, 8/34, P = 0.007) than those without fungal infections. The result of the multivariate analysis showed that the incidence of fungal infections in KTRs with COVID-19 was independently correlated with age (increased by 10 years, OR = 2.221), history of diabetes mellitus (OR = 12.293), ARDS (OR = 12.849), and bacterial co-infections (OR = 30.461). Conclusion: Compared to KTRs without fungal infections, those with COVID-19-related fungal infections had worse clinical courses and less favorable results. The conditions including bacterial co-infections, ARDS, older age, and comorbidity of diabetes mellitus increased the incidence of secondary fungal infections.</abstract><keywords/></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Zhou F, Yu T, Du R, et al., 2020, Clinical Course and Risk Factors for Mortality of Adult Inpatients with COVID-19 in Wuhan, China: A Retrospective Cohort Study. Lancet, 395(10229): 1054–1062.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B2" content-type="article"><label>2</label><element-citation publication-type="journal"><p>Raja MA, Mendoza MA, Villavicencio A, et al., 2021, COVID-19 in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis of Current Literature. Transplant Rev (Orlando), 35(1): 100588.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B3" content-type="article"><label>3</label><element-citation publication-type="journal"><p>Yang X, Yu Y, Xu J, et al., 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 8(5): 475–481.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B4" content-type="article"><label>4</label><element-citation publication-type="journal"><p>Wang J, Yang Q, Zhang P, et al., 2020, Clinical Characteristics of Invasive Pulmonary Aspergillosis in Patients with COVID-19 in Zhejiang, China: A Retrospective Case Series. Crit Care, 24(1): 299.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B5" content-type="article"><label>5</label><element-citation publication-type="journal"><p>Raut A, Huy NT, 2021, Rising Incidence of Mucormycosis in Patients with COVID-19: Another Challenge for India Amidst the Second Wave? Lancet Respir Med, 9(8): e77.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B6" content-type="article"><label>6</label><element-citation publication-type="journal"><p>Naveen KV, Saravanakumar K, Sathiyaseelan A, et al., 2022, Human Fungal Infection, Immune Response, and Clinical Challenge-A Perspective During COVID-19 Pandemic. Appl Biochem Biotechnol, 194(9): 4244–4257.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B7" content-type="article"><label>7</label><element-citation publication-type="journal"><p>Cruzado Vega LL, Santos Garcia A, 2022, SARS-CoV-2 and Aspergillus Pneumonia in Kidney Transplantation: More Frequent Than We Think? Nefrologia (Engl Ed), 42(3): 359–360.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B8" content-type="article"><label>8</label><element-citation publication-type="journal"><p>Casalini G, Giacomelli A, Ridolfo A, et al., 2021, Invasive Fungal Infections Complicating COVID-19: A Narrative Review. J Fungi (Basel), 7(11): 921.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B9" content-type="article"><label>9</label><element-citation publication-type="journal"><p>Shishido AA, Mathew M, Baddley JW, 2022, Overview of COVID-19-Associated Invasive Fungal Infection. Curr Fungal Infect Rep, 16(3): 87–97.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B10" content-type="article"><label>10</label><element-citation publication-type="journal"><p>Hoenigl M, Seidel D, Sprute R, et al., 2022, COVID-19-Associated Fungal Infections. Nat Microbiol, 7(8): 1127–1140.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B11" content-type="article"><label>11</label><element-citation publication-type="journal"><p>Maartens G, Wood MJ, 1991, The Clinical Presentation and Diagnosis of Invasive Fungal Infections. J Antimicrob Chemother, 28(Suppl A): 13–22.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B12" content-type="article"><label>12</label><element-citation publication-type="journal"><p>Koehler P, Bassetti M, Chakrabarti A, et al., 2021, Defining and Managing COVID-19-Associated Pulmonary Aspergillosis: The 2020 ECMM/ISHAM Consensus Criteria for Research and Clinical Guidance. Lancet Infect Dis, 21(6): e149–e162.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B13" content-type="article"><label>13</label><element-citation publication-type="journal"><p>White PL, Dhillon R, Cordey A, et al., 2021, A National Strategy to Diagnose Coronavirus Disease 2019-Associated Invasive Fungal Disease in the Intensive Care Unit. Clin Infect Dis, 73(7): e1634–e1644.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B14" content-type="article"><label>14</label><element-citation publication-type="journal"><p>Wilmes D, Coche E, Rodriguez-Villalobos H, et al., 2021, Fungal Pneumonia in Kidney Transplant Recipients. Respir Med, (185): 106492.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B15" content-type="article"><label>15</label><element-citation publication-type="journal"><p>Tragiannidis A, Gkampeta A, Vousvouki M, et al., 2021, Antifungal Agents and the Kidney: Pharmacokinetics, Clinical Nephrotoxicity, and Interactions. Expert Opin Drug Saf, 20(9): 1061–1074.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B16" content-type="article"><label>16</label><element-citation publication-type="journal"><p>Gangneux JP, Dannaoui E, Fekkar A, et al., 2022, Fungal Infections in Mechanically Ventilated Patients with COVID-19 During the First Wave: The French Multicentre MYCOVID Study. Lancet Respir Med, 10(2): 180–190.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B17" content-type="article"><label>17</label><element-citation publication-type="journal"><p>Chong WH, Saha BK, Neu KP, 2022, Comparing the Clinical Characteristics and Outcomes of COVID-19-Associate Pulmonary Aspergillosis (CAPA): A Systematic Review and Meta-Analysis. Infection, 50(1): 43–56.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B18" content-type="article"><label>18</label><element-citation publication-type="journal"><p>Singh S, Verma N, Kanaujia R, et al., 2021, Mortality in Critically Ill Patients with Coronavirus Disease 2019-Associated Pulmonary Aspergillosis: A Systematic Review and Meta-Analysis. Mycoses, 64(9): 1015–1027.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B19" content-type="article"><label>19</label><element-citation publication-type="journal"><p>Trujillo H, Fernandez-Ruiz M, Gutierrez E, et al., 2021, Invasive Pulmonary Aspergillosis Associated with COVID-19 in a Kidney Transplant Recipient. Transpl Infect Dis, 23(2): e13501.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B20" content-type="article"><label>20</label><element-citation publication-type="journal"><p>Kellum JA, Lameire N, 2013, Diagnosis, Evaluation, and Management of Acute Kidney Injury: A KDIGO Summary (Part 1). Crit Care, 17(1): 204.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B21" content-type="article"><label>21</label><element-citation publication-type="journal"><p>Ranieri VM, Rubenfeld GD, Thompson BT, et al., 2012, Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA, 307(23): 2526–2533.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B22" content-type="article"><label>22</label><element-citation publication-type="journal"><p>Permpalung N, Chiang TPY, Manothummetha K, et al., Invasive Fungal Infections in Inpatient Solid Organ Transplant Recipients With COVID-19: A Multicenter Retrospective Cohort. Transplantation, 108(7): 1613–1622.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B23" content-type="article"><label>23</label><element-citation publication-type="journal"><p>Avery RK, Chiang TPY, Marr KA, et al., 2021, Inpatient COVID-19 Outcomes in Solid Organ Transplant Recipients Compared to Non-Solid Organ Transplant Patients: A Retrospective Cohort. Am J Transplant, 21(7): 2498–2508.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B24" content-type="article"><label>24</label><element-citation publication-type="journal"><p>Pennington KM, Martin MJ, Murad MH, et al., Risk Factors for Early Fungal Disease in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis. Transplantation, 108(4): 970–984.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B25" content-type="article"><label>25</label><element-citation publication-type="journal"><p>Fernandez-Ruiz M, Andres A, Loinaz C, et al., 2020, COVID-19 in Solid Organ Transplant Recipients: A Single-Center Case Series from Spain. Am J Transplant, 20(7): 1849–1858.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B26" content-type="article"><label>26</label><element-citation publication-type="journal"><p>Chong WH, Saha BK, Ananthakrishnan R, et al., 2021, State-of-the-Art Review of Secondary Pulmonary Infections in Patients with COVID-19 Pneumonia. Infection, 49(4): 591–605.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B27" content-type="article"><label>27</label><element-citation publication-type="journal"><p>Frydrych LM, Bian G, O’Lone DE, et al., 2018, Obesity and Type 2 Diabetes Mellitus Drive Immune Dysfunction, Infection Development, and Sepsis Mortality. J Leukoc Biol, 104(3): 525–534.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B28" content-type="article"><label>28</label><element-citation publication-type="journal"><p>Schwartz MD, Emerson SG, Punt J, et al., 2020, Decreased Naïve T-cell Production Leading to Cytokine Storm as Cause of Increased COVID-19 Severity with Comorbidities. Aging Dis, 11(4): 742–745.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B29" content-type="article"><label>29</label><element-citation publication-type="journal"><p>Li H, Liu L, Zhang D, et al., 2020, SARS-CoV-2 and Viral Sepsis: Observations and Hypotheses. Lancet, 395(10235): 1517–1520.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B30" content-type="article"><label>30</label><element-citation publication-type="journal"><p>Nimmo A, Gardiner D, Ushiro-Lumb I, et al., 2022, The Global Impact of COVID-19 on Solid Organ Transplantation: Two Years Into a Pandemic. Transplantation, 106(7): 1312–1329.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B31" content-type="article"><label>31</label><element-citation publication-type="journal"><p>Marjot T, Webb GJ, Barritt AS, et al., 2021, COVID-19 and Liver Disease: Mechanistic and Clinical Perspectives. Nat Rev Gastroenterol Hepatol, 18(5): 348–364.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B32" content-type="article"><label>32</label><element-citation publication-type="journal"><p>Austermeier S, Pekmezovic M, Porschitz P, et al., 2021, Albumin Neutralizes Hydrophobic Toxins and Modulates Candida albicans Pathogenicity. mBio, 12(3): e0053121.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B33" content-type="article"><label>33</label><element-citation publication-type="journal"><p>Deshmukh H, Speth C, Sheppard DC, et al., 2020, Aspergillus-Derived Galactosaminogalactan Triggers Complement Activation on Human Platelets. Front Immunol, (11): 550827.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B34" content-type="article"><label>34</label><element-citation publication-type="journal"><p>Algin O, Gokalp G, Topal U, 2011, Signs in Chest Imaging. Diagn Interv Radiol, 17(1): 18–29.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B35" content-type="article"><label>35</label><element-citation publication-type="journal"><p>Negm EM, Mohamed MS, Rabie RA, et al., 2023, Fungal Infection Profile in Critically Ill COVID-19 Patients: A Prospective Study at a Large Teaching Hospital in a Middle-Income Country. BMC Infect Dis, 23(1): 246.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B36" content-type="article"><label>36</label><element-citation publication-type="journal"><p>Tang L, Yin Z, Hu Y, et al., 2020, Controlling Cytokine Storm Is Vital in COVID-19. Front Immunol, (11): 570993.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B37" content-type="article"><label>37</label><element-citation publication-type="journal"><p>Yang X, Tian S, Guo H, 2021, Acute Kidney Injury and Renal Replacement Therapy in COVID-19 Patients: A Systematic Review and Meta-Analysis. Int Immunopharmacol, (90): 107159.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B38" content-type="article"><label>38</label><element-citation publication-type="journal"><p>Duarsa GWK, Sugianto R, Yusari IGAAA, et al., 2023, Predictor Factor for Worse Outcomes in Kidney Transplant Recipients Infected with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis. Transpl Immunol, (76): 101739.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B39" content-type="article"><label>39</label><element-citation publication-type="journal"><p>Tolou-Ghamari Z, 2012, Nephro and Neurotoxicity of Calcineurin Inhibitors and Mechanisms of Rejections: A Review on Tacrolimus and Cyclosporin in Organ Transplantation. J Nephropathol, 1(1): 23–30.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B40" content-type="article"><label>40</label><element-citation publication-type="journal"><p>Fishman JA, 2017, Infection in Organ Transplantation. Am J Transplant, 17(4): 856–879.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B41" content-type="article"><label>41</label><element-citation publication-type="journal"><p>Zhang H, Zhang Y, Wu J, et al., 2020, Risks and Features of Secondary Infections in Severe and Critical Ill COVID-19 Patients. Emerg Microbes Infect, 9(1): 1958–1964.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B42" content-type="article"><label>42</label><element-citation publication-type="journal"><p>Tejerina EE, Abril E, Padilla R, et al., 2019, Invasive Aspergillosis in Critically Ill Patients: An Autopsy Study. Mycoses, 62(8): 673–679.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B43" content-type="article"><label>43</label><element-citation publication-type="journal"><p>Thompson GR, Miceli MH, Jiang J, et al., 2023, Secondary Invasive Fungal Infection in Hospitalised Patients with COVID-19 in the United States. Mycoses, 66(6): 527–539.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B44" content-type="article"><label>44</label><element-citation publication-type="journal"><p>Clancy CJ, Nguyen MH, 2020, Coronavirus Disease 2019, Superinfections, and Antimicrobial Development: What Can We Expect? Clin Infect Dis, 71(10): 2736–2743.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B45" content-type="article"><label>45</label><element-citation publication-type="journal"><p>Prattes J, Wauters J, Giacobbe DR, et al., 2022, Risk Factors and Outcome of Pulmonary Aspergillosis in Critically Ill Coronavirus Disease 2019 Patients-A Multinational Observational Study by the European Confederation of Medical Mycology. Clin Microbiol Infect, 28(4): 580–587.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B46" content-type="article"><label>46</label><element-citation publication-type="journal"><p>Stephens ML, Mathew A, Banerjee D, et al., 2022, COVID-Associated Pulmonary Aspergillosis and Herpes Simplex Virus Pneumonia in a Renal Transplant Recipient. Transpl Infect Dis, 24(6): e13978.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B47" content-type="article"><label>47</label><element-citation publication-type="journal"><p>Akbar AN, Gilroy DW, 2020, Aging Immunity May Exacerbate COVID-19. Science, 369(6501): 256–257.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B48" content-type="article"><label>48</label><element-citation publication-type="journal"><p>Villanego F, Mazuecos A, Perez-Flores IM, et al., 2021, Predictors of Severe COVID-19 in Kidney Transplant Recipients in the Different Epidemic Waves: Analysis of the Spanish Registry. Am J Transplant, 21(7): 2573–2582.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B49" content-type="article"><label>49</label><element-citation publication-type="journal"><p>Shafiekhani M, Shekari Z, Boorboor A, et al., 2022, Bacterial and Fungal Co-Infections with SARS-CoV-2 in Solid Organ Recipients: A Retrospective Study. Virol J, 19(1): 35.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B50" content-type="article"><label>50</label><element-citation publication-type="journal"><p>Ballering AV, van Zon SKR, Olde Hartman TC, et al., 2022, Persistence of Somatic Symptoms After COVID-19 in the Netherlands: An Observational Cohort Study. Lancet, 400(10350): 452–461.</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
