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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 2  |  Page : 579-583
Coronavirus disease 2019 infection in kidney transplant recipients: A clinical case series

1 Department of Nephrology, Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran
2 Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
3 Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
4 Department of Radiology, Mazandaran University of Medical sciences, Sari, Iran

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Date of Web Publication11-Jan-2022


Kidney transplant recipients appear to be at increased risk for severe coronavirus disease 2019 (COVID-19) illness due to some factors such as comorbidities and chronic immunosuppression. Here, we report four cases of COVID-19 infection in kidney transplant recipients. The one case in this series with the high D-dimer levels and receiving tacrolimus had the worst outcome among reported patients. Other patients had better outcomes that probably due to the effect of immunosuppressive therapy in the prevention of COVID-19-induced cytokine storm. It was suggested that a high D-dimer level occurred in critical patients and likely prognostic and also, the immunosuppressive effect of some treatment regimens.

How to cite this article:
Asgharpour M, Afshar ZM, Ebrahimpour S, Babazadeh A, Oladzad S. Coronavirus disease 2019 infection in kidney transplant recipients: A clinical case series. Saudi J Kidney Dis Transpl 2021;32:579-83

How to cite this URL:
Asgharpour M, Afshar ZM, Ebrahimpour S, Babazadeh A, Oladzad S. Coronavirus disease 2019 infection in kidney transplant recipients: A clinical case series. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Jan 28];32:579-83. Available from: https://www.sjkdt.org/text.asp?2021/32/2/579/335475

   Introduction Top

The World Health Organization announced a coronavirus disease 2019 (COVID-19) infection outbreak due to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) as a pandemic on March 11, 2020. The COVID-19 patients included cases with a fever fever, chills, dry cough, sore throat, shortness of breath, and patients with upper/lower respiratory symptoms with radiological manifestations as single or double-sided multi-lobular infiltrations on computed tomography (CT) scan or plain chest radiography and a positive real-time reverse transcription polymerase chain reaction test.[1] There is currently no approved drug available for the treatment of COVID-19 infection but, some regimens used in different centers in the world such as favipiravir and remdesivir.

There is limited data on whether transplant recipients with COVID-19. However, lessons learned from the Middle East respiratory syndrome and SARS outbreaks can provide understanding about the shedding of these viruses and higher rates of related mortality in transplant patients. Kidney transplant recipients appear to be at high risk for COVID-19 infection due to immunosuppression and comorbidities.[2] Some reports of COVID-19 in kidney transplant recipients are now emerging. Here, we report four cases of COVID-19 infection in kidney transplant recipients.

   Case Reports Top

Case 1

A 50-year-old woman with a recipient of a kidney transplant three years earlier with dyspnea (blood oxygen saturation of 92%) in late March 2020 was admitted to the hospital. Her history did not include close contact with confirmed COVID-19 cases. The chest CT scan showed small areas of faint ground-glass opacities (GGOs) in the periphery of both lungs with linear opacities in the lower lobes, accompanied by mild bilateral effusion.

Her laboratory tests on admission included lymphopenia (600/mm3); hemoglobin (Hb), 11.2 g/dL; platelet count, 148,000/μL; serum creatinine, 1 mg/dL; D-dimer, 525 ng/mL; C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), 39 mg/L and 50 mm/h, respectively, and normal electrolytes and liver function tests. She had received kidney transplant three years ago and has been in triple immunosuppressive therapy with cyclosporin- A (CsA), mycophenolate mofetil (MMF), and prednisolone since the transplantation.

The patient isolated for respiratory illness and underwent broad-spectrum antimicrobial agents along with antiviral treatment for COVID-19, including kaletra (lopinavir plus ritonavir), and ribavirin. Also, MMF was discontinued, the CsA dose was reduced and hydrocortisone was replaced instead of prednisolone. Her dyspnea gradually subsided and her lymphopenia and inflammatory markers improved and she was discharged in good condition after eight days.

Case 2

A 63-year-old man with a recipient of a kidney transplant two years earlier with a 10-day complaint of chest tightness, nonproductive cough, nausea, vomiting, and fever in March 2020 was admitted to the hospital.

His oxygen saturation (SpO2) was 93% on admission. He had been received CsA, MMF, and prednisolone. A lung computerized tomography (CT) scan revealed multiple bilateral GGOs with subpleural distribution, more prominent in the lower lobes.

Naso-pharyngeal swab tested for SARS-CoV-2 RNA amplification was positive. Her laboratory data were as follows: white blood cell, 6.100 ×109/L with 12% lymphocytes; Hb, 11.7 g/dL; platelet, 180000/μL; D-dimer, 1868 ng/mL; CRP, 40 mg/L; ESR, 40 mm/h; serum creatinine, 1 mg/dL; sodium, 127 mEq/L, and potassium 4.3 mEq/L.

She received antivirals (Kaletra two 200 mg tablets BD, for 5–14 days) and antimicrobials; however, he developed a transient QT-interval prolongation, which abated with no intervention. His condition improved gradually and he was discharged to continue therapy out-patiently.

Case 3

A 63-year-old man with a recipient of a kidney transplant 10 years earlier with fever, cough, and epigastric pain for five days, without shortness of breath was admitted to the hospital. His comorbidities included diabetes mellitus (DM), hypertension (HTN), hyperlipidemia, and ischemic heart failure undergoing coronary-artery bypass grafting.

Furthermore, he reported a history of tuberculosis 14 years earlier. He received valsartan, metoprolol, atorvastatin, spironolactone, prednisolone, MMF, and cyclosporine. His pulse oximetry revealed SpO2 of 95% on room air. He had a lymphopenia and a moderate increase of inflammatory markers on admission. Nasopharyngeal swab tested for SARS-CoV-2 RNA amplification was positive. A lung CT scan revealed multiple patchy bilateral GGOs were consistent with COVID-19. He was started on meropenem, vancomycin, lopinavir plus ritonavir, and hydroxychloroquine. His immunosuppressive agents’ doses were adjusted. After three days, his fever subsided and he was discharged two days after defervescence.

Case 4

A 42-year-old woman with a history of end-stage kidney disease in 2013 and on hemodialysis for four years with a recipient of a kidney transplant three years ago was admitted to hospital.

Her medications included tacrolimus, MMF, and prednisolone. During an outbreak of COVID-19, she presented with one week of dyspnea, myalgia, nausea, and vomiting. Also, the laboratory tests included hypoxemia, thrombocytopenia, leukocytosis, relative lymphopenia, and high levels of D-dimer. However, naso-pharyngeal swab tested for SARS-CoV-2 RNA amplification was negative.

The chest CT scan showed multifocal crazy paving pattern as manifested by GGOs with superimposed interlobular and intralobular septal thickening in both lungs with peripheral distribution, mostly in middle and lower lobes and also dense consolidations in the lower lobes [Figure 1]. On suspicion of COVID-19 infection, supplementary oxygen, teicoplanin, imipenem, azithromycin, hydroxychloroquine, oseltamivir, and lopinavir plus ritonavir were administered along with tacrolimus dose reduction, MMF omission from her immuno-suppressant regimen, and corticosteroid dose increase. Nine days later, her hypoxemia worsened, resulting in the intensive care unit admission, continuous positive airway pressure, hemoperfusion, and receiving multiple doses of intravenous immunoglobulin (IVIg). Ultimately she recovered partially 16 days after admission.
Figure 1: The computed tomography of the chest revealed that multifocal crazy paving pattern manifested by ground-glass opacities with superimposed interlobular and intralobular septal thickening in both lungs.

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The authors obtained all appropriate consent forms from the patients, their guardians and relatives for the publication of the case reports.

   Discussion Top

The first admission of a kidney transplant patient with COVID-19 pneumonia to our treatment center in north Iran took place in March 2020. The cases comprised two men and two women, who were managed impatiently. Of these four patients, one of them needed ICU admission because of severe hypoxemia nonresponsive to nasal oxygen and needing of invasive ventilation. Furthermore, the others were managed noninvasively only with oxygen through a mask or nasal cannula.

The risk of acquiring severe COVID-19 infection among renal transplant recipients is higher than in the general population, due to immunosuppressant therapy, end-stage kidney disease, and other comorbidities, especially HTN and diabetes.[3]

Among our patients, only case number 3 had a history of DM, HTN, and ischemic heart disease.

Regarding the baseline lymphopenia commonly present in transplant recipients due to immunosuppressive therapy, prediction of the clinical outcome of posttransplant COVID-19 patients regarding the lymphopenia would be unreliable; all of our cases had severe lymphocyte depletion, which might have been the result of both immunosuppressant’s effects and COVID-19 infection. On the other hand, leukocytosis may be a bad prognostic factor, which was true only in case number 4. D-dimer is a significant prognostic factor in cases with suspected COVID-19 infection.[4] Values of higher than 3500 ng/mL indicate an unfavorable outcome.[5] Interestingly, among our cases, only one patient with high D-dimers progressed to a worse condition.

There are currently no studies investigating radiographic findings especially in immuno-compromised individuals with COVID-19 infection. However, almost all post-transplant patients with COVID-19 infection had a typical lung CT scan appearances, except for some of them with normal CT findings in the beginning stage of the disease.[6]

All four patients reported in this series had characteristic radiographic patterns, but with the last case manifested crazy paving pattern which refers to the appearance of GGOs with superimposed interlobular septal thickening and intralobularseptal thickening, highly suggestive of COVID-19 in the compatible settings.

Managing immunosuppressive agents in transplant cases is a challenging decision, for which some parameters such as the severity of infection, age, underlying diseases, and time duration posttransplant should be taken into account.[7] There are no definite recommendations for dose reduction or discontinuation of these agents in the course of COVID-19 infection; however, stopping antiproliferative agents such as MMF and imuran, increasing the dose of prednisolone and stopping or decreasing the dose of calcineurin inhibitors such as tacrolimus and cyclosporine is currently the favored approach at the time of admission in most centers, as performed in our cases.[8]

On the other hand, there is always a concern for graft rejection because of immunosuppression reduction; however, saving the patients’ lives in this potentially lethal virus outbreak might be the most important issue and the decision should be made individually. The antiviral treatment used in our patients was the same as in other COVID-19 patients (chloroquine and kaletra), but due to the risk of transplant rejection, interferons were not used and IVIg was used instead.

IVIg might be applied in deteriorating patients to prevent progression to critical illness.[9] This therapy was used for our last patient since she did not respond to comprehensive antiviral and antibacterial therapy, supportive care, and immunosuppression adjustment. Fortunately, this approach improved our patient’s outcome and saved her life.

One of the agents utilized in the immuno-suppressive regimen of post-transplant patients is the calcineurin inhibitor class (tacrolimus and cyclosporin A). The inhibitory effects of CsA on coronaviruses proliferation have been proved.[10] Hence, those patients on CsA might have better outcomes, compared with others receiving tacrolimus, as seen in the current report.

A significant precautionary strategy in transplant patients undergoing COVID-19 treatment is the probable elevation of calcineurin inhibitor levels by lopinavir plus ritonavir. Therefore, blood levels of these immuno-suppressants should be monitored closely. In all our patients, serum tacrolimus or CsA levels were measured to avoid toxicity. Despite the background of immunosuppression, our patients showed a good prognosis that was similar to reports from other transplant centers and that could be due to inhibition of the cytokine storm induced by the virus by immuno-suppressive regimens.

   Conclusion Top

The one case in this series with high D-dimer levels and receiving tacrolimus had the worst outcome among reported patients. It was suggested that the prognostic value of some laboratory tests and the immunosuppressive effects of some regimens. The management of COVID-19 infection in posttransplant cases is further complicated than expected. Many efforts should be carried out to control the SARS-CoV-2 spread and avoid posttransplant infections, particularly when the vaccine is not available.

Conflict of interest: None declared.

   References Top

Javanian M, Bayani M, Shokri M, et al. Clinical and laboratory findings from patients with COVID-19 pneumonia in Babol North of Iran: A retrospective cohort study. Rom J Intern Med 2020;58:161-7.  Back to cited text no. 1
Akalin E, Azzi Y, Bartash R, et al. COVID-19 and Kidney Transplantation. N Engl J Med 2020;382:2475-7.  Back to cited text no. 2
Alberici F, Delbarba E, Manenti C, et al. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney Int 2020;97:1083-8.  Back to cited text no. 3
Sakka M, Connors JM, Hékimian G, et al. Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and pooled analysis. J Med Vasc 2020;45:268-74.  Back to cited text no. 4
Yao Y, Cao J, Wang Q, et al. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: A case control study. J Intensive Care 2020;8:49.  Back to cited text no. 5
Nacif LS, Zanini LY, Waisberg DR, et al. COVID-19 in solid organ transplantation patients: A systematic review. Clinics (Sao Paulo) 2020;75:e1983.  Back to cited text no. 6
Johnson KM, Belfer JJ, Peterson GR, Boelkins MR, Dumkow LE. Managing COVID-19 in renal transplant recipients: A review of recent literature and case supporting corticosteroidsparing immunosuppression. Pharmacotherapy 2020;40:517-24.  Back to cited text no. 7
Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M. COVID-19 infection in kidney transplant recipients. Kidney Int 2020;97: 1076-82.  Back to cited text no. 8
Cao W, Liu X, Bai T, et al. High-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019. Open Forum Infect Dis 2020;7:ofaa102.  Back to cited text no. 9
Cure E, Kucuk A, Cumhur Cure M. Cyclosporine therapy in cytokine storm due to coronavirus disease 2019 (COVID-19). Rheumatol Int 2020;40:1177-9.  Back to cited text no. 10

Correspondence Address:
Arefeh Babazadeh
Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol
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DOI: 10.4103/1319-2442.335475

PMID: 35017357

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