肾移植受者新型冠状病毒奥密克戎变异株感染181例单中心临床诊治经验

Diagnosis and treatment of kidney transplant recipients infected with novel coronavirus Omicron variant:a single-center experience of 181 cases

目的探讨奥密克戎变异株传播期间肾移植受者新型冠状病毒(以下简称新冠病毒)感染后病情进展的危险因素,以及抗RNA病毒药物在阻断肾移植受者新冠病毒感染后病情进展中的作用。方法回顾性分析2022年12月4日至2023年1月31日在清华大学附属北京清华长庚医院器官移植中心肾移植科随访的232例肾移植受者新冠病毒感染的临床资料,观察时间为新冠病毒感染后30 d。根据肾移植受者是否确诊新冠病毒感染,分为感染组(181例)和未感染组(51例);感染组受者,根据是否进展为重型,分为病情进展组(23例)和病情稳定组(158例)。对比分析各组受者性别、年龄、身体质量指数、移植术后时间、基础病(高血压、糖尿病、冠心病、慢性肺部疾病史)、吸烟史、是否使用抗RNA病毒药物及种类等资料。采用单因素和多因素logistic回归分析法分析肾移植受者新冠病毒感染临床分型进展的独立危险因素。结果232例肾移植受者中新冠病毒感染率为78.0%(181/232),临床分型为:轻型112例、中型46例、重型21例、危重型2例,重症率为12.7%(23/181)。新冠病毒感染后,年龄≥65岁的13例受者中有5例由轻/中型进展为重型,年龄<65岁的168例受者中有18例进展为重型;患有糖尿病的68例受者中有13例(19.1%)由轻/中型进展为重型,无糖尿病的113例中受者有10例(8.8%)进展为重型,二者比较,差异有统计学意义(P=0.045)。单因素logistic分析结果显示,年龄≥65岁(OR=5.21,95%CI:1.54~17.64,P=0.008)和患有糖尿病(OR=2.44,95%CI:1.003~5.911,P=0.049)可显著增加新冠病毒感染受者由轻/中型向重型进展发生的危险;多因素logistic分析结果显示,年龄≥65岁(OR=4.03,95%CI:1.14~14.34,P=0.031)是新冠病毒感染受者由轻/中型进展为重型的独立危险因素。181例轻/中型新冠病毒感染受者,有18例使用奈玛特韦/利托那韦、10例使用阿兹夫定进行抗RNA病毒治疗,均未进展为重型;153例未使用抗RNA病毒药物治疗,有23例(15.0%)进展为重型,差异有统计学意义(P=0.028)。23例重型受者中,有14例使用奈玛特韦/利托那韦、2例使用阿兹夫定进行抗RNA病毒治疗,前者均未进展为危重型,后者中有1例进展为危重型并死亡;7例未使用抗RNA病毒药物的受者中有1例进展为危重型并死亡,另外6例均未进展为危重型。结论年龄≥65岁或患有糖尿病的肾移植受者,新冠病毒感染后由轻/中型进展为重型的风险更大。其中,年龄≥65岁是新冠病毒感染受者由轻/中型进展为重型的独立危险因素。肾移植受者在新冠病毒感染轻/中型阶段使用奈玛特韦/利托那韦或阿兹夫定进行抗病毒治疗,可显著降低重症率。在重型阶段使用奈玛特韦/利托那韦进行治疗仍有效。

Objective To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4,2022 to January 31,2023 at Department of Renal Transplantation,Organ Transplantation Center,Beijing Tsinghua Changgung Hospital.Inclusion criteria were age≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19,KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases).In infection group,recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender,age,body mass index(BMI),time after transplantation,underlying diseases(history of hypertension,diabetes mellitus,coronary heart disease&chronic lung disease),smoking history and dosing of anti-RNA virus agents were collected.Pearson χ^(2) test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients.Results Among 232 KT recipients,infection rate of COVID-19 was 78.0%(181/232).The clinical classification was mild(112 cases),moderate(46 cases),severe(21 cases)and critical(n=2 cases).The severe rate was 12.7%(23/181).After infection with COVID-19,the proportion of KT recipients aged≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)].The difference was statistically significant(P=0.014);The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)].The difference was statistically significant(P=0.045).Univariate Logistic analysis showed similar results.Age≥65 years(OR=5.21,95%CI:1.54-17.64,P=0.008)or diabetes mellitus(OR=2.44,95%CI:1.003-5.911,P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age≥65 years(OR=4.03,95%CI:1.14-14.34,P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients,18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However,none of them progressed to severe;153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant(P=0.028).Among 23 severe cases,14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death;1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness.Conclusions KT recipients aged≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them,age≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.