Different clinical presentations of two renal transplant recipients with coronavirus disease 2019: a case report

A 57-year-old man who underwent a living-related kidney transplant due to chronic glomerulonephritis in 2013, was admitted to Union hospital in Wuhan on February 11, 2020, complaining of an unexplained fever (up to a maximum of 39.2 °C) for 6 days. This was followed by cough, fatigue, nausea, and shortness of breath, while no chest pain, diarrhea, or abdominal pain were present. The patient had no history of smoking or alcohol abuse, cardiovascular disease, or pulmonary disease. His immunosuppressive regimen consisted of tacrolimus 1.5 mg orally twice daily (trough serum levels 5 ng/mL ~ 8 ng/mL during the past year), and mycophenolate mofetil 0.75 g twice daily until 2 days prior to his visit. And there was no acute rejection or augmented or adjusted on immunosuppression in recent 2 years prior to infection. Two days ago, the patient went to the outpatient center due to consistent fever and all his immunosuppressants were discontinued as the doctor advised.

On admission, his chest computed tomography (CT) scan showed multiple patchy ground-glass opacities in the bilateral lungs (Fig. 1a). Laboratory testing revealed an absolute lymphocyte count of 0.98 × 10⁹/L (normal range, 1.1–3.2 × 10⁹/L), serum creatinine 142 μmolL (normal range, 59–104 μmolL), and estimated glomerular filtration rate (eGFR) of 49.3 ml/min/1.73 m² (normal range, > 90 ml/min/1.73 m²). A nasopharyngeal swab specimen was obtained and sent for detection of SARS-CoV-2 according to the CDC guidelines [5]. In brief, throat-swab specimens from the upper respiratory tract were obtained and maintained in a viral-transport medium. SARS-CoV-2 was confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) as previously reported [6]. Eight respiratory pathogens were tested using IgM and IgG antibody tests including respiratory syncytial virus, influenza virus A, influenza virus B, adenovirus, legionella pneumoniae, mycoplasma, parainfluenza, and chlamydia. These negative results indicated that no co-infection was present. The patient was diagnosed with COVID-19 according to the positive detection of SARS-CoV-2 and chest CT display.

Combination therapy was initiated with immunoglobin (200 mg/kg/day), methylprednisolone (40 mg daily), recombinant human interferon-alpha 2b (10 million IU daily), arbidol hydrochloride (0.6 g daily), and biapenem (0.6 g daily), for 12 days, in order to inhibit virus replication and implement empirical antibiotic treatment. Four days after admission, the alanine aminotransferase level increased to 76 U/L (normal range, 0–40 U/L), and by day 8 it had increased further to 93 U/L, which indicated hepatic damage. Glutathione was then initiated by 1.8 g intravenous injection daily for 9 days. Immunosuppression was resumed on day 2 after admission, including tacrolimus 1 mg twice daily, and mycophenolate mofetil 0.375 g twice daily (adjusted to 0.75 g twice daily on day 10). High-flow humidification oxygen administration was used to prevent acute hypoxic respiratory failure.

During treatment, the patient’s symptoms resolved with body temperature falling to between 36.3 °C and 37.1 °C, and his cough, nausea, and shortness of breath disappeared. The laboratory results were also improved, in particular, the lymphocyte count, serum creatinine, eGFR, and alanine aminotransferase (Fig. 2). And the kidney allograft function also improved during the course of therapy. On day 4, the second chest CT scan indicated that his pneumonia had aggravated (Fig. 1b). On day 9, the third chest CT scan (Fig. 1c) showed significant improvement of bilateral ground glass opacities compared to the previous scans. Based on the persistent negative results of SARS-CoV-2 RT-PCR on days 7 and 9, as well as the lung lesions partially decreased, the patient was discharged on day 13. To date, the patient has been in good health at home for 4 months.

A 55-year-old man, who underwent a renal transplant from a deceased donor in 2013 due to chronic kidney disease presented to the emergency department of Tongji Hospital on February 13, 2020, complaining of oliguria (< 400 ml) and a cough for 10 days, and shortness of breath for 2 days. He did not complain of fever, sore throat, or diarrhea. The patient had a history of surgery for urinary tract obstruction due to kidney stones and concomitant myocardial infarction in 2019. His immunosuppression was mycophenolate mofetil 0.5 g twice daily, tacrolimus 2.5 mg twice daily (trough serum levels 5 ng/mL ~ 10 ng/mL during the past year), and methylprednisolone 8 mg once daily. And there was no acute rejection or augmented or adjusted on immunosuppression in recent 6 months prior to infection.

On admission, the patient received a 7 L/min of oxygen administration to maintain an oxygen saturation of 95%, with a blood pressure of 82/50 mmHg and a heart rate of 99 bpm. His chest CT scan showed bilateral diffuse ground-glass changes (Fig. 3a). Laboratory testing revealed an absolute lymphocyte count of 0.31 × 10⁹/L, serum creatinine 247 μmolL, eGFR 24.4 ml/min/1.73 m², high-sensitivity troponin I (hsTNI) 312.8 pg/mL (normal range, < 34.2 pg/mL), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 70,000 pg/mL (normal range, < 161 pg/mL). Nasopharyngeal swabs on admission were positive for SARS-CoV-2 RT-PCR. Then veno-venous hemodialysis and hemofiltration therapy was initiated. He developed arrhythmia (atrial fibrillation with rapid ventricular rate) on day 3 and promptly received synchronized cardioversion and noninvasive mechanical ventilation with bi-level positive airway pressure therapy. On day 5, the level of hsTNI increased to 1580.3 pg/mL and the NT-proBNP level was > 70,000 pg/mL, which indicated acute congestive heart failure. After diuresis, cardiotonics, steroids, and respiratory support, the patient’s clinical condition improved and he was transferred to the general ward for infectious diseases.

The patient received treatment with immunoglobin (300 mg/kg/day from day 6 to day 13 and adjusted to 75 mg/kg/day from day 14 to day 22), arbidol hydrochloride (0.6 g daily from day 16 to day 22), recombinant human interferon-alpha2 b (10 million IU daily from day 8 to day 22), and antimicrobial therapy consisting of biapenem (0.6 g daily from day 14 to day 21) and micafungin (50 mg daily from day 16 to day 22) according to the clinical events. Antimicrobial doses were adjusted to the patient’s creatinine clearance, and the immunosuppressive regimen was adjusted to the clinical condition, including CT scans, laboratory results, FK506 blood concentration, and symptoms (Fig. 4). On day 14, due to the persistent lymphocyte depletion and an abnormal ratio of lymphocyte subsets, the dose of immunoglobin was reduced to 75 mg/kg/day, and mycophenolate mofetil to 0.5 g daily. On day 16, mycophenolate mofetil was discontinued and tacrolimus was reduced to 3 mg daily due to the development of clinically suspected bacterial and mycotic pneumonia (invasive pulmonary aspergillosis according to the positive result of serum galactomannan test), and re-adjusted (mycophenolate mofetil 0.5 g daily and tacrolimus 4 mg daily) on day 22 due to the negative results of SARS-CoV-2 RT-PCR (Fig. 4).

During treatment, the patient’s symptoms resolved and laboratory tests, including D-dimer, C-reactive protein (CRP), and interleukin 6 (IL-6), were improved significantly with days, although the lymphocyte count did not change significantly until the day of discharge (Fig. 5a). And the results of serum creatinine and eGFR were improved significantly, which indicated the kidney allograft function also improved. However, when comparing the lymphocyte subsets, the percentages of CD3⁺ T cells, CD3⁺CD4⁺ T cells (helper/inducer T cells), and the ratio of CD3⁺CD4⁺ T cells/CD3⁺CD8⁺ T cells decreased with the clinical course of the disease, while the percentage of CD3⁺CD8⁺ T cells (suppressor/cytotoxic T cells) and CD16⁺CD56⁺ T cells (natural killer cells, NK) increased with the clinical course of the disease (Fig. 5b). On day 10, the second chest CT scan indicated that his pneumonia aggravated with multiple patchy opacities and local consolidation (Fig. 3b). On day 18, the third chest CT scan showed significant improvement of multiple patchy opacities (Fig. 3c). On day 25, the fourth chest CT scan showed local consolidation decreased compared to the third scan (Fig. 3d). In addition, the high flow oxygen administration was removed on day 26. Given the remission of the disease, as well as the persistent negative results of SARS-CoV-2 RT-PCR, the patient was discharged on day 28. To date, the patient has been in good health at home for 3 months.