key: cord-355655-l684uy4h authors: Ning, Ling; Liu, Lei; Li, Wenyuan; Liu, Hongtao; Wang, Jizhou; Yao, Ziqin; Zhang, Shengyu; Zhao, Desheng; Nashan, Björn; Shen, Aizong; Liu, Lianxin; Li, Lei title: Novel coronavirus (SARS‐CoV‐2) infection in a renal transplant recipient: Case report date: 2020-05-08 journal: Am J Transplant DOI: 10.1111/ajt.15897 sha: doc_id: 355655 cord_uid: l684uy4h An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS‐CoV‐2) started in Wuhan, China, with cases now confirmed in multiple countries. The clinical course of patients remains to be fully characterized, clinical presentation ranges from asymptomatic infection to acute respiratory distress syndrome and acute renal failure, and no pharmacological therapies of proven efficacy yet exist. We report a case of SARS‐CoV‐2 infection in a renal transplant recipient with excellent outcome. This case states the importance of close monitoring of the concentration of cyclosporine in patients treated with lopinavir/ritonavir; the routine treatment of corticosteroid can be continued. This is a rare report of SARS‐CoV‐2 infection in a renal transplant recipient. Further data are needed to achieve better understanding of the impact of immunosuppressive therapy on the clinical presentation, severity, and outcome of SARS‐CoV‐2 infections in solid organ transplant recipients. A 29-year-old male patient, with a clinical history of arterial hypertension and later chronic kidney disease, underwent hemodialysis for 9 months and then received a living kidney transplant donated by his mother on December 27, 2018. His routine immunosuppressive regimen consisted of mycophenolate mofetil 0.5 g q12h, cyclosporine (CsA) q12h (75 mg every morning and 75 mg/100 mg alternating every other night), and methylprednisolone 8 mg daily. Simultaneously, he was given a maintenance treatment with esomeprazole 20 mg daily, aspirin 0.1 g daily, metoprolol succinate 47.5 mg daily, felodipine 5 mg twice daily, valsartan 80 mg every night, and diammonium glycyrrhizinate 150 mg 3 times daily. He presented to the fever clinic of the local hospital in Fuyang city, Anhui province, on February 6, 2020, complaining of generalized fatigue and chills for 2 days and a low-grade fever of 37.7℃ After admission, he was started on broad-spectrum antibiotic therapy with moxifloxacin in addition to trimethoprim/sulfamethoxazole; the immunosuppressive regimen and maintenance treatment were not changed. Mild chest tightness, nasal stuffiness, loss of appetite, nausea, and vomiting developed 12 hours later ( Figure 1 ). His laboratory testing revealed an elevated white cell count, mild thrombocytopenia, hyponatremia, and hypoalbuminemia (Table 1) Table 1 ). The 24-hour urine volume on hospital day 3 was 500 mL. To improve the oliguria and hyponatremia, individually tailored fluid administration based on real-time urine volume was conducted, and 24-hour urine volume for hospital days 4 and 5 was 2000 and 2500 mL, respectively. Chest CT was performed on hospital day 5 ( Figure 2B ) and revealed extensive but slightly improved ground-glass shadowing over both lungs and a strip-like sign over bilateral superior lobes and right lower lobe. Both the sputum and oropharyngeal swab specimens later tested negative on RT-PCR for SARS-CoV-2. Given unavailable laboratory testing of CsA concentration in blood, our major concern was the metabolic interactions on cytochrome P450 (CYP) between CsA and lopinavir/ritonavir. This issue was addressed in a multidisciplinary team meeting, performed online on hospital day 6, in which it was decided to discontinue esomeprazole and reduce lopinavir/ritonavir by 25% to 750 mg daily. Dosage of baseline immunosuppression remained unchanged. Laboratory results on day 6 of hospitalization showed improved creatinine level and hyponatremia; again, the sputum and oropharyngeal swab specimens tested negative on RT-PCR for SARS-CoV-2. Given the stable clinical presentation, chest CT revealed significant improvement on day 12 of hospitalization ( Figure 2C) White-cell count ( The value in the patient was below normal. Figure 2D ). Both oropharyngeal swab and sputum were negative for SARS-CoV-2 on RT-PCR twice, on February 25 and February 26. C 0 and C 2 of CsA were measured on February 26; C 0 was 260.58 ng/ mL and C 2 was 319.19 ng/mL. No changes were made to the dosing at this time, and further evaluation will be performed. We report a case of COVID-19 occurring in a kidney transplant recipient. Diagnosis was confirmed using RT-PCR assays. Although the source of his SARS-CoV-2 infection is unknown, evidence of personto-person transmission has been confirmed. 4 Specific drugs to treat SARS-CoV-2 will take several years to develop and evaluate. In an attempt to treat the COVID-19, interferon and ribavirin were deemed to be not suitable for a renal transplantation recipient due to their side effects, including the potential to trigger an acute rejection. Therefore, the protease inhibitors lopinavir/ritonavir were initiated based on Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (trial version 5). Lopinavir and ritonavir are the inhibitors of CYP3A enzyme 12 causing irreversible inhibition of CYP3A4 with increased blood levels of ciclosporin/tacrolimus. 13 While we were unable to monitor C 0 of CsA in blood because laboratory testing was restricted by biosafety level, we empirically adjusted the dosage of lopinavir/ritonavir to three quarters of the recommended dose. We retrospectively tested CsA levels on stored specimens which coincidentally had been collected from one day before and after the treatment with lopinavir/ritonavir. We found the C 0 of CsA before treatment within the patients usual CsA exposure while the C 2 level after treatment was higher than the C 2 recommended level. 14 To confirm the interaction between CsA and lopinavir/ritonavir, follow-up monitoring of C 0 and C 2 levels were implemented 1 week after discharge (8 days after lopinavir/ritonavir discontinued). The C 0 was elevated, but C 2 was decreased indicating that lopinavir/ritonavir may strongly interact via CYP450 with the concentration of CsA even after discontinuation of the protease inhibitors. Nevertheless, no serious hepatic and renal dysfunction was observed in our case and we assume further normalization of CsA levels. Methylprednisolone was routinely used as baseline immunosuppression in this case, although its use for the treatment of SARS-CoV-2 infection remains controversial. 15 No clinical data exist to indicate that net benefit is derived from corticosteroids in the treatment of respiratory infection due to coronavirus included SARS-CoV and MERS-CoV. 15 Furthermore, corticosteroid treatment may be associated with delayed clearance of MERS-CoV viral RNA from respiratory tract secretions. 16 In conclusion, we report COVID-19 in a renal transplant recipient successfully treated with lopinavir/ritonavir. The patient had a relatively mild illness, atypical pneumonia resolved rapidly under the antiviral therapy and an excellent clinical recovery was observed. No significant complications were found during the infection although baseline immunosuppression was continued. Maintenance treatment with corticosteroids was continued as well since no negative impact was found. Furthermore, lopinavir/ritonavir has a strong effect on CsA blood concentration, hence these patients need close monitoring and if necessary, adjustment such as dosage reduction or discontinuation. More data are needed to gain better understanding of SARS-CoV-2 infections in solid organ transplant recipients. The authors of this manuscript have no conflict of interest to disclose as described by the American Journal of Transplantation. Data sharing is not applicable to this article as no new data were created or analyzed in this study. 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