COVID-19 associated acute transplant failure after AB0-incompatible living donor kidney transplantation – a case report

Boss et al. BMC Nephrology (2023) 24:19 https://doi.org/10.1186/s12882-023-03070-z BMC Nephrology Open Access CASE REPORT COVID-19 associated acute transplant failure after AB0-incompatible living donor kidney transplantation – a case report Kristina Boss1*, Margarethe Konik2, Jan Hinrich Bräsen3, Jessica Schmitz3, Christiane Jürgens1, Andreas Kribben1, Oliver Witzke2, Sebastian Dolff2 and Anja Gäckler1 Abstract Introduction Immunosuppressive therapy is associated with an increased risk of severe courses of SARS-CoV-2 infection, with frequently delayed viral clearance. We report a case of an acute kidney transplant failure in persistent SARS-CoV-2 infection in a patient with absolute B-cell depletion after administration of rituximab for AB0incompatible living donor kidney transplantation. Case presentation A 34-year-old unvaccinated patient is diagnosed with SARS-CoV-2 infection four months after kidney transplantation. With only mild symptoms and an estimated glomerular filtration rate (eGFR) of 44 ml/min/1.73 m2, therapy with molnupiravir was initially given. Within the next eight weeks, transplant biopsies were performed for acute graft failure. These showed acute T-cell rejection with severe acute tubular epithelial damage with only mild interstitial fibrosis and tubular atrophy (BANFF cat. 4 IB), and borderline rejection (BANFF cat. 3). A therapy with prednisolone and intravenous immunoglobulins was performed twice. With unchanged graft failure, the third biopsy also formally showed BANFF cat. 4 IB. However, fluorescence in situ hybridization detected SARS-CoV-2 viruses in large portions of the distal tubules. After nine weeks of persistent COVID-19 disease neither anti-SARS-CoV-2 IgG nor a SARS-CoV-2-specific cellular immune response could be detected, leading to the administration of sotrovimab and remdesivir. Among them, SARS-CoV-2 clearance, detection of IgG, and improvement of graft function were achieved. Conclusion Lack of viral clearance can lead to complications of SARS-CoV-2 infection with atypical manifestations. In kidney transplant patients, before initiating therapy, the differential diagnoses of “rejection” and “virus infection” should be weighed against each other in an interdisciplinary team of nephrologists, infectious diseases specialists and pathologists. Keywords AB0-incompatible, Kidney transplantation, COVID-19, Rejection, Case report *Correspondence: Kristina Boss 1 Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany 2 Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany 3 Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Boss et al. BMC Nephrology (2023) 24:19 Introduction Covid-19 produces high burden of inflammation. In transplant recipients this effect may be alleviated by immunosuppressive drugs [1]. On the other hand, immunosuppressive therapy is associated with an increased risk of severe courses of SARS-CoV-2 infection, with frequently delayed viral clearance and the COVID19 related mortality rate is higher in kidney transplant recipients than in nontransplant patients [4]. We report a case of an acute kidney transplant failure in persistent SARS-CoV-2 infection in a patient with absolute B-cell depletion after administration of rituximab for AB0incompatible living donor kidney transplantation. Case presentation A 34-year-old unvaccinated man is diagnosed with SARSCoV-2 infection by a naso-pharyngeal swab and reverse transcription polymerase chain reaction (PCR) assay four months after transplantation. The immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and prednisone. Hospitalisation for remdesivir therapy was refused by the patient. A SARS-CoV-2 neutralizing antibody was not available at this time (Jan 2022), so with an eGFR of 44 ml/min/1.73 m2 and only mild symptoms, a therapy with molnupiravir was initially given. The patient did not report any drug-related adverse reactions. There were no thrombocytopenia or elevated transaminases. In the following weeks there was a progressive deterioration in transplant function, so that the patient was finally admitted to hospital four weeks after onset of infection. Blood analysis showed leukopenia and an absolute B-cell depletion. The first transplant biopsy demonstrated an acute T-cell rejection with severe acute tubular epithelial damage with only mild interstitial fibrosis and tubular atrophy (BANFF cat. 4 IB). The patient received prednisolone intravenously over three days with a cumulative dose of 1 g. As the transplant function did not improve, a second biopsy was performed, which demonstrated a borderline rejection (BANFF cat. 3). This was followed by a second prednisolone therapy as well as the administration of intravenous immunoglobulins (iVIG) with a cumulative dose of 60 g over three days. Tacrolimus trough levels were measured at short intervals and were within the therapeutic range of 5–7 ng/ml. There was no evidence for donor specific binding HLA IgG antibodies. Approximately eight weeks after the onset of infection, the patient developed a COVID-19 pneumonia with bacterial superinfection, which was treated anti-infectively with tazobactam/piperacillin and clarithromycin and immunomodulatory with dexamethasone (6 mg/d for 7 days) and renewed iVIG. Several microbiologic tests have been performed without Page 2 of 5 identification of a certain pathogen. So, blood and urine analyses, fungal diagnostics in blood and bronchoalveolar lavage and mycoplasma tests remained negative. With unchanged highly restricted graft function, a third biopsy showed formally acute T-cell rejection, BANFF cat. 4 IB. However, fluorescent in situ hybridization (FISH), using the XRNA SARS-CoV-2 RNA FISH probe (MetaSystems Probes, Altlußheim, Ger (...truncated)