key: cord-0920923-lnhr0qka authors: Namazee, Najmeh; Mahmoudi, Hilda; Afzal, Payman; Ghaffari, Sina title: Novel Corona Virus 2019 pneumonia in a kidney transplant recipient date: 2020-05-13 journal: Am J Transplant DOI: 10.1111/ajt.15999 sha: bdcd83eb11bdd040fbd83eca9f6bd0cf30607412 doc_id: 920923 cord_uid: lnhr0qka COVID 19 pandemic is spreading worldwide and the impact of the disease in transplant patients is evolving. In this case report, we presented a 63 years old female kidney transplant recipient who presented with dyspnea and cough and diagnosed with COVID 19 pneumonia. On the 4(th) day of admission, the patient’s condition worsened. Therefore, the immunosuppressive medications were discontinued, and hydrocortisone started. The patient died on the 5(th) day. A 63 years old woman, deceased donor kidney transplant recipient twenty years ago, was admitted with dyspnea and cough for seven days before admission. She didn't report headaches, fever, chills, or diarrhea. She had no history of recent travel or close contact to confirmed COVID 19 cases. The only significant previous medical history was hypertension. Her current medications were mycophenolate mofetil (Cellcept) 500mg twice daily and Cyclosporine 75 mg twice daily. Her physical exam was as follows: Temperature: 37.1°c, Pulse Rate: 80 b/min, Accepted Article (figure) The patient was admitted with an impression of COVID 19 and an oropharyngeal swab test for SARS-CoV-2 was taken. She was sent to the COVID 19 special ward and was given Hydroxychloroquine 400mg single dose orally, Kaletra (Lopinavir/Ritonavir) 400/100 mg twice daily orally and Oseltamivir 75 mg daily orally. She also received intravenous Cefepime 500mg twice daily. The pre-treatment through the level of cyclosporine was 95 ng/mL which was in target level range (70-150 ng/mL) recommended by our national protocol. The adjustments based on drug-drug interactions (DDI) were applied and the cyclosporine dose was reduced to 50 mg twice daily. The cyclosporine blood through the level was kept between 90-100 ng/ml. The pretreatment through blood level of CellCept (mycophenolate mofetil) was 1.3 mg/L. We reduced the dose to 500mg once daily. Given the potential risk of prolongation of QT by both hydroxychloroquine and lopinavir, we performed daily EKG to assess the corrected QT interval (QTc). Echocardiography showed mild pericardial effusion with Ejection Fraction of 60%. Abdominopelvic ultrasound revealed increased parenchymal echogenicity in the transplanted kidney. On the second day of the admission, the patient developed a rise in serum Creatinine (3.1 mg/dl) and O2 saturation dropped to 78% with an oxygen mask with a reservoir bag. The patient was alert and communicative, So Supportive measures continued, and Adjusted dose vancomycin was added to the medications. On the 4th day of admission, she developed respiratory distress, increased work of breathing, dyspnea, and oliguria, and she was intubated and underwent 24 hours This article is protected by copyright. All rights reserved telemetry. Creatinine raised to 3.4 mg/dl. The CRP level was 78 mg/L, ERS 85, LDH 574, PT 14.5 second, PTT 40 seconds, and platelet level was 387000/ mL. Cellcept and Cyclosporine were discontinued, and Hydrocortisone 100 mg every 8 hours started. On the 5th day, the patient developed foamy bloody discharge through the endotracheal tube, respiratory acidosis, and rise in creatinine (4.4 mg/dl). Unfortunately, the patient became bradycardic and was coded for cardiopulmonary arrest. CPR was unsuccessful. The postmortem examination is unlikely to be necessary on a deceased patient with confirmed COVID 19 infection given the risk of transmission of infectious pathogens during and after the postmortem examination. 1However, in this case, we determined that postmortem test should be pursued and asked the relatives for the permission, but the patient's surrogate refused. The overall clinical presentation, laboratory and Chest CT scan findings of the COVID 19 in the patient discussed above were similar to non-transplant cases. Regarding the treatment, we administered the standard treatment which has been recommended by the National COVID 19 interim management guidance. Among these, IL6 seems to be a leading trigger of the inflammatory cascade, which may increase alveolar-capillary blood-gas exchange dysfunction 10,11. In the presented case, we could not assess the existence of cytokine storm because IL6 monitoring was not available in our center. Although, the development of lung foamy blood discharge, hypoxia, and increased levels of inflammatory markers such as ESR, CRP, and LDH could propose the presence of the inflammatory response initiated by pro-inflammatory Cytokines such as IL6. In the presence of cytokine storm, IL-6 targeting therapies such as tocilizumab may play an important role to control acute respiratory distress syndrome (ARDS) in transplant patients contracted COVID 195 . In the presented case, it is not clear that if the patient might benefit from discontinuation of immunosuppressant upon admission. According to The Transplantation society, changes in immunosuppression are not well studied in transplant patients and adjustment of dose reduction has to balance the consequences of rejection 12. The presented patient had a risen creatinine, proteinuria, and increased parenchymal echogenicity in the transplanted kidney at the time of admission which could be accompanied by a higher risk of rejection with discontinuation of immunosuppressive medication. Therefore, we decided to reduce but not discontinue the immunosuppressants. Although we reduced the doses of immunosuppressants, nephrotoxicity secondary to drug-drug interaction could not be ruled out. The other potential explanation of kidney failure of the patient could be direct damage of COVID 19 to the kidney. It has been shown that COVID19 not only causes pneumonia but also it may cause direct damage to other organs such as the heart, liver, kidneys, as well as the blood and the immune system 8,9,13. Therefore, one possible explanation of kidney failure, in this case, could be the aggravation of kidney function due to the cytopathic effect of SARS-COV-2 on kidney 14. In summary, we discussed some factors that might contribute to the unfortunate death of the presented patient such as acute respiratory distress syndrome (ARDS) exacerbated by an inflammatory response and renal failure secondary to drug nephrotoxicity or direct injury to the kidney by SARS-COV-2. Moreover, we discussed our treatment strategy in terms of administration of Lopinavir-Ritonavir as a potentially effective antiviral medication and reduction of immunosuppressants. We tried to balance between the treatment of the patient's COVID 19 infection and the risk of her Accepted Article kidney rejection or provoked an inflammatory response. Although the treatment of the patient was not successful, we believed that the reporting of unsuccessful case treatments is crucial in order to obtain the maximum knowledge to protect the population of kidney transplant recipients. Disclosure: The Authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. This article is protected by copyright. All rights reserved The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Autopsy in suspected COVID-19 cases Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Clinical features of patients infected with 2019 novel coronavirus in Wuhan Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory medicine COVID-19) for Transplant Clinicians Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China Kidney disease is associated with in-hospital death of patients with