重症新型冠状病毒感染患者服用奈玛特韦/利托那韦后病毒核酸变化的相关因素 ——一项单中心回顾性队列研究

Related factors of viral nucleic acid change in critically ill patients with SARS-CoV-2 infection after treatment with Nirmatrelvir/Ritonavir:a single center retrospective cohort study

目的描述重症新型冠状病毒(新冠病毒)感染患者服用奈玛特韦/利托那韦后核酸转阴、复阳情况,并探讨核酸不能转阴和复阳的相关因素及预后情况。方法采用单中心回顾性队列研究,纳入2022年12月7日至2023年1月27日北京大学第一医院收治的符合新冠病毒感染重型、危重型诊断和分型并服用奈玛特韦/利托那韦满5 d的年龄≥16岁的患者。从电子病例系统采集患者基本特征和临床资料,采用Kaplan-Meier曲线绘制核酸转阴时间曲线;选取P<0.10的指标纳入多因素Logistic回归模型,分析各因素与核酸持续阳性和核酸复阳的关系。结果共纳入新冠病毒感染重型患者31例、危重型患者37例。重型、危重型患者服用奈玛特韦/利托那韦后核酸转阴中位时间均为6.0 d,15 d病毒核酸转阴率分别为93.5%和86.5%。7例(11.3%)患者出现核酸复阳,其中重型1例,危重型6例。将7例复阳患者和6例核酸不能转阴患者与55例核酸持续转阴患者进行比较,选取淋巴细胞计数(LYM)最低值、D-二聚体最高值、降钙素原(PCT)最高值、首次阳性最低Ct值和除高血压、心脏病以外的其他心血管疾病等P<0.10的指标纳入多因素Logistic回归分析,显示发病时LYM下降〔优势比(OR)=0.146,95%可信区间(95%CI)为0.031~0.689,P=0.015〕和PCT升高(OR=2.008,95%CI为1.042~3.868,P=0.037)是核酸不能转阴或核酸复阳的独立危险因素。核酸持续阳性和复阳患者机械通气比例(84.6%比38.2%)、有创通气比例(69.2%比25.5%)明显高于核酸持续转阴患者(均P<0.01),但两组间机械通气时间和有创通气时间差异无统计学意义。76.9%的核酸持续阳性和复阳患者需要转入重症监护病房(ICU)治疗,高于核酸持续转阴组患者ICU转入率(50.9%),且ICU住院时间也略长〔d:13.0(10.3,24.3)比11.0(5.3,23.0),P>0.05〕。结论发病时LYM降低和PCT升高是重症新冠病毒感染患者核酸不能转阴及核酸复阳的独立危险因素,核酸不能转阴和核酸复阳患者的临床预后不佳,应引起临床医师的重视。

ObjectiveTo describe negative conversion and rebound of patients with severe and critical acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection after treatment with Nirmatrelvir/Ritonavir,and to analyze related factors associating with failure of SARS-CoV-2 negative conversion and relapse and prognosis.MethodsA single center retrospective cohort study was conducted.Patients aged≥16 years old who were diagnosed with severe or critical SARS-CoV-2 infection and took Nirmatrelvir/Ritonavir for 5 days in Peking University First Hospital from December 7,2022 to January 27,2023,were included.General characteristics and clinical data were collected from electronic medical record system.The Kaplan-Meier curve of SARS-CoV-2 negative conversion was drawn.Factors with P<0.10 were incorporated into multivariate Logistic regression model to analyze the relationship between the factors and persistent nucleic acid positive and rebound.ResultsA total of 31 severe and 37 critical SARS-CoV-2 infection patients were included.The median duration from initiation of Nirmatrelvir/Ritonavir to negative conversion of SARS-CoV-2 for both was 6.0 days,and the negative conversion rate on day 15 was 93.5%and 86.5%,respectively.SARS-CoV-2 rebound was observed in 7 patients(11.3%),among whom were 1 severe patient and 6 critical patients.The above 7 patients with SARS-CoV-2 rebound and 6 patients with failure of SARS-CoV-2 negative conversion were compared with 55 patients with persistent negative conversion.Factors with P<0.10,including the lowest lymphocyte count(LYM),the highest D-dimer,the highest procalcitonin(PCT),the lowest Ct value,cardiovascular diseases other than hypertension and coronary heart disease,were incorporated into multivariate Logistic regression analysis.The decreased LYM[odds ratio(OR)=0.146,95%confidence interval(95%CI)was 0.031-0.689,P=0.015]and the increased PCT(OR=2.008,95%CI was 1.042-3.868,P=0.037)were revealed to be independent risk factors of the failure of SARS-CoV-2 negative conversion or rebound.The proportion of mechanical ventilation and invasive ventilation were significantly higher in patients with persistent SARS-CoV-2 infection or rebound than those in patients with SARS-CoV-2 negative conversion(84.6%vs.38.2%,69.2%vs.25.5%,both P<0.01),but no significant difference in mechanical ventilation and invasive ventilation duration was observed.Compared with the patients with SARS-CoV-2 negative conversion,more patients with persistent SARS-CoV-2 infection or rebound were admitted to intensive care unit(ICU,76.9%vs.50.9%),and length of ICU stay in patients with persistent SARS-CoV-2 infection or rebound tended to be longer[days:13.0(10.3,24.3)vs.11.0(5.3,23.0),P>0.05].ConclusionsThe decreased LYM and increased PCT are independent risk factors for the failure of SARS-CoV-2 negative conversion or rebound in patients with severe and critical SARS-CoV-2 infection.Attention should be paid to these patients for their poor prognosis.