探讨肾移植术后重型及危重型新型冠状病毒感染(COVID-19)受者临床诊疗经验。

回顾性分析空军军医大学第一附属医院泌尿外科2022年12月至2023年1月收治的14例重型或危重型COVID-19肾移植受者临床资料。收集受者人口学资料、临床表现以及实验室检查、胸部CT检查及宏基因组二代测序结果。正态分布计量资料采用配对t检验进行比较，非正态分布计量资料采用配对样本Wilcoxon符号秩和检验进行比较。P<0.05为差异有统计学意义。

14例受者入院时咽拭子新型冠状病毒(以下简称新冠病毒)核酸检测均为阳性，且静息状态下吸入空气指氧饱和度均≤93%，诊断为重型，其中病例1及14在治疗过程中出现氧合指数进行性下降，合并移植肾功能不全，需无创呼吸机辅助通气及透析治疗，诊断为危重型。14例受者中10例入院后血清肌酐较前基本维持稳定；2例入院时血清肌酐较基线水平分别上升30%和50%；2例入院后血清肌酐进行性上升，分别升至600和700 μmol/L，须行肾脏替代治疗。14例受者入院时及治疗过程中均接受胸部CT检查，最常见的表现为双肺近胸膜下多发磨玻璃密度影，部分患者以双下肺及背侧受累较为明显。14例受者在明确诊断后予常规心电及血氧饱和度监测、氧疗、对症支持治疗、抗病毒治疗、免疫抑制剂调整、免疫调节剂使用、抗菌药物、抗凝及其他药物治疗。经过治疗后，12例诊断为重型COVID-19受者一般情况均较入院前好转，全身症状及呼吸道症状减轻，静息状态下指氧饱和度≥95%，胸部CT检查较前明显吸收或稳定。12例重型COVID-19受者治疗前及出院前外周血淋巴细胞计数、血清肌酐、血清淀粉蛋白A、C-反应蛋白、纤维蛋白原和IL-6差异均有统计学意义(t＝5.74、3.65、6.41、7.86和7.40，Z＝－2.35，P均<0.05)。2例诊断为危重型COVID-19受者出院后仍需要规律行肾脏替代治疗。14例受者对治疗方案耐受总体尚可，未出现因不良反应停药事件，治疗过程中未出现死亡。

肾移植受者感染新冠病毒后，在调整免疫抑制剂用量基础上应尽早使用抗病毒药物进行治疗。对于发病时间较长，且已进展为重症的受者，Paxlovid联合巴瑞替尼仍有较好的治疗效果。

To evaluate the clinical experience in the diagnosis and treatment of COVID-19 in kidney transplant recipients.

The clinical data of 14 kidney transplant recipients diagnosed with severe or critical COVID-19 were retrospectively analyzed. The demography data, clinical manifestations, and test results of laboratory examination, chest CT and metagenomic next-generation sequencing of the 14 kidney transplant recipients were collected. The paired t-test was used to compare the normally distributed measurement data, the paired sample Wilcoxon rank-sum test was used to compare non-normally distributed measurement data. P<0.05 indicates that the difference is statistically significant.

14 recipients had positive results for novel coronavirus nucleic acid detection of throat swabs, and the oxygen saturation levels at rest were all ≤93%. They were diagnosed with severe cases. Among the 14 recipients, case 1 and case 14 had progressive decline in oxygenation index during treatment and developed allograft dysfunction, and both of them required non-invasive ventilator-assisted ventilation as well as dialysis and therefore diagnosed with critical COVID-19. Among the 14 recipients, 10 cases had stable serum creatinine levels during admission; 2 cases had serum creatinine levels that increased by 30% and 50% compared to baseline; 2 cases had progressive increases in serum creatinine levels, which rose to 600 and 700 μmol/L, respectively, and required renal replacement therapy. Chest CT was performed on all recipients upon admission and during treatment. The most common manifestation was multiple subpleural ground-glass opacities in both lungs, with more obvious involvement in the lower lungs and dorsal regions in some recipients. After diagnosis, all recipients received routine electrocardiogram and blood oxygen saturation monitoring, oxygen therapy, symptomatic supportive treatment, antiviral treatment, immunosuppressant adjustment, immunomodulator use, antibacterial drugs therapy, anticoagulant treatment, and other drug treatments. After treatment, the general condition of the 12 recipients diagnosed with severe cases improved compared to before admission. Systemic symptoms and respiratory symptoms were relieved; oxygen saturation levels at rest were all ≥95%; chest CT showed obvious absorption or stabilization. The peripheral blood lymphocyte counts, serum creatinine levels, serum amyloid A levels, C-reactive protein levels, fibrinogen levels, and IL-6 levels showed statistically significant differences between before treatment and before discharge (t=5.74, 3.65, 6.41, 7.86 and 7.40, Z=-2.35, all P<0.05). The two critical cases required regular renal replacement therapy after discharge. The treatment plan was generally well-tolerated by the recipients without any drug withdrawal events due to adverse reactions during treatment. No deaths occurred during the treatment process.

Early administration of antiviral agent is critical for improving the prognosis. Treatment of Paxlovid with Baritinib might still be beneficial for kidney recipient with prolonged course and those already developed severe symptoms.