key: cord-0834623-7jadf7mr
authors: Kijima, Yu; Shimizu, Tomokazu; Kato, Shinya; Sekido, Eri; Kano, Kana; Toguchi, Makoto; Horiuchi, Toshihide; Nozaki, Taiji; Omoto, Kazuya; Inui, Masashi; Toma, Hiroshi; Iida, Shoichi; Takagi, Toshio
title: Suspected pneumonia caused by COVID-19 after kidney transplantation: A Case Report
date: 2021-09-30
journal: Transplant Proc
DOI: 10.1016/j.transproceed.2021.09.009
sha: 2cd28b4e8bde933ff673ae2465956511e1786852
doc_id: 834623
cord_uid: 7jadf7mr

BACKGROUND: Coronavirus disease-2019 (COVID-19) infection may become more severe in those who have undergone kidney transplantation than in the general population. False-negative reverse transcription-polymerase chain reaction (RT-PCR) results have been reported for COVID-19 infection.Patients might carry infection even though RT-PCR results are negative. CASE REPORT: A 65-year-old man with a 19-year history of ABO-incompatible kidney transplantation presented with fever and arthralgia. Although the RT-PCR result was negative, a focal slit glass shadow in the left upper lobe on computed tomography (CT) suggested COVID-19 pneumonia. His symptoms did not improve until after 10 days and CT showed multiple slit-glass shadows in the bilateral lung fields. However, RT-PCR remained negative. The patient was admitted and mycophenolate mofetil was discontinued. Anticoagulants were administered on the 3(rd) day of hospitalization. Due to poor oxygenation, the patient was intubated in the intensive care unit on the 5th day, and sivelestat sodium was administered. The patient was extubated on the 12(th) day following improvement in oxygenation. There was no exacerbation, and CT showed improvements on the 51(st) day. CONCLUSIONS: We report a case of pneumonia with suspected COVID-19 infection 18 years after living-donor kidney transplantation. If COVID-19 is suspected, infection control and aggressive therapeutic interventions should be undertaken with the possibility of a positive result in mind.

The coronavirus disease-2019 (COVID-19) infection can be more severe in patients who have undergone kidney transplantation than in the general population. In addition, false-negative reverse transcription-polymerase chain reaction (RT-PCR) has been reported even in those with active COVID-19 infection. Patients might still have COVID-19 infection even though RT-PCR results are negative. In this study, we report a case of suspected COVID-19 pneumonia after a living donor kidney transplantation.

A 65-year-old man underwent ABO-incompatible kidney transplantation for chronic renal failure due to IgA nephropathy. Medical history was notable for recurrent IgA nephropathy (bilateral palatine tonsillectomy was performed), adenocarcinoma of the lung (left thoracoscopic partial pneumonectomy was performed), cerebral infarction, brain tumor, hypertension, dyslipidemia, and diabetes mellitus. The patient was maintained on an immunosuppressive therapy regimen that included tacrolimus, mycophenolate mofetil (MMF), and methylprednisolone. Nineteen years later, the patient presented with fever and arthralgia. Computed tomography (CT) showed a focal slit glass shadow in the left upper lobe, suggesting COVID-19 pneumonia, although RT-PCR was negative. Considering the positive pneumococcal antigen in the urine, the patient was diagnosed with pneumococcal pneumonia and started on oral amoxicillin-clavulanic acid. The symptoms did not improve despite 10 days of treatment, and the patient's fever and cough persisted. CT showed multiple slit-glass shadows in the bilateral lung fields (Figure 1 ), leading to the diagnosis of COVID-19 pneumonia; however, the RT-PCR performed on the same day was negative. Based on the clinical symptoms and CT findings, the patient was admitted to the hospital as an emergency case with a diagnosis of suspected COVID-19 pneumonia. Physical examination revealed a Glasgow Coma Scale score of E4V5M6; body temperature, 38.2°C; blood pressure, 118/78 mmHg; pulse, 88 beats/min; and blood oxygen saturation (SPO 2 ), 97% (in room air). Laboratory data showed an increase in the white blood cells (13,120 /μL) and C-reactive protein (CRP) (9.50 mg/dL) due to inflammatory reaction. Blood urea nitrogen (46.3 mg/dL) and serum creatinine (2.22 mg/dL) levels were elevated ( Table 1 ). The patient's clinical course is shown in Figure   2 .

Ciprofloxacin and bactolamine (ST fixed-dose combination) were started on the 1 st day of hospitalization after initially suspecting bacterial pneumonia and Pneumocystis jirovecii pneumonia and MMF was discontinued. As a septicemic treatment, massive intravenous immunoglobulin (IVIG) and pulsed steroid therapy were administered on the 2 nd day. The antimicrobial agent was changed to meropenem, and anticoagulants (nafamostat mesylate) were administered due to the upward trend of CRP in the blood test on the 3 rd day. The patient was transferred from the general ward to the intensive care unit (ICU) because of poor oxygenation with a SpO 2 of 90% under an oxygen mask with a flow rate of 8 L/min and was intubated and placed on a ventilator on the 5 th day. Sivelestat was administered as a treatment for acute respiratory distress syndrome (ARDS). CT showed markedly enlarged frosted margins in the bilateral lung fields on the 5 th day (Figure 3 ). Following improvement in the general condition, the patient was extubated and transferred to a general ward the following day, with good oxygenation on the 13 th day. No exacerbation was observed. A CT scan to evaluate pneumonia on the 51 st day revealed a decrease in the density of the bilateral lung slit and infiltrate shadows and a tendency for improvement ( Figure 4 ).

The patient was discharged on the 59 th day, with the renal function restored to the level before treatment.

In this study, we encountered a case of pneumonia suspected to be caused by a COVID-19 infection that developed 18 years after kidney transplantation.

False-negative RT-PCR results have been reported even in hospitalized patients with clinically diagnosed COVID-19 [1, 2] . False-negative results have also been confirmed after two negative RT-PCR results [1] . The accuracy of specimen collection and the number of antigens might affect the test results. In this case, there was no change from the initial diagnosis. Although we confirmed a negative RT-PCR at the time of initial diagnosis and hospitalization, it is possible that the test would have been positive if the patient had been retested. Even if RT-PCR is negative, COVID-19 can be clinically suspected based on the findings of a chest CT [3] . In this case, COVID-19 pneumonia was suspected based on clinical symptoms and imaging findings. COVID-19 infection after living donor kidney transplantation is associated with a higher mortality rate (28%) than in the general population or in patients older than 70 years [4] . Treatment with mycophenolic acid and everolimus has been reportedly reduced or discontinued (68%), and calcineurin inhibitors discontinued (32%) [5] . Currently, there are no treatment options available for COVID-19 infection, and adjuvant therapy includes corticosteroid/anti-cytokine treatment and immunosuppressant/immunoglobulin therapy [6] . Remdesivir, dexamethasone, and baricitinib have been approved for use in Japan. Heparin is indicated in patients with moderate disease II and above [7] . Anticoagulation has been reported to be the most crucial treatment for reducing COVID-19-related mortalities [8] . We administered anticoagulants (nafamostat mesylate) to our patient for COVID-19 pneumonia due to the lack of established treatment methods at the time. However, we subsequently changed the treatment to IVIG, steroid pulse, and anticoagulants (nafamostat mesylate). Sivelestat sodium has been reported to be effective against acute lung injury and ARDS [9] . A previous study reported the efficacy of sivelestat sodium in cases of severe COVID-19 pneumonia requiring ventilator use. Our patient was administered sivelestat at the time of admission to the ICU [10] . The patient's general condition improved, and the patient was extubated and transferred to a general ward the following day with good oxygenation on the 13 th day. 

Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19

False-negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: Rather than recurrence

Use of chest CT in combination with negative RT-PCR assay for the 2019 novel coronavirus but high clinical suspicion

Covid-19 and kidney transplantation

COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium

Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review

Guide to the Treatment of COVID-19 version 5

COVID-19 Treatment Combinations and Associations with Mortality in a Large Multi-Site Healthcare System

Elaspor®) for the treatment of acute respiratory distress syndrome (ARDS)

Infection control and treatment of severe COVID-19 pneumonia requiring ventilator use in a city hospital

The authors would like to thank Editage (www.editage.jp) for English language editing. This case was presented at the 85 th meeting of the Saitama Branch of the Japanese Urological Association.

The authors declare no conflicts of interest.

Informed consent: Written informed consent was obtained from the patient for publication of this case report and accompanying images.Registry and the registration no. of the study/trial: Not applicable.

 Figure 4