Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study
Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study
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2020 年 1 月至 3 月中国浙江省 SARS-CoV-2 感染患者的病毒载量动态和疾病严重程度：回顾性队列研究
DOI：
10.1136/bmj.m1443
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发表时间：
2020-04-21
影响因子：
105.7
通讯作者：
Liang, Tingbo
中科院分区：
文献类型：
--
作者：
Zheng, Shufa;Fan, Jian;Liang, Tingbo
摘要目的评价浙江省2019年严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染患者在疫情前4个月疾病进展不同阶段的病毒载量。设计回顾性队列研究。地点中国浙江省新冠肺炎患者定点医院。参与者96例连续入院的实验室确诊的SARS-CoV-2感染患者：22例轻度疾病和74例重度疾病。数据于二零二零年一月十九日至二零二零年三月二十日收集。主要结果测量呼吸道、粪便、血清和尿液样本中的核糖核酸（RNA）病毒载量。将循环阈值（核酸浓度的量度）绘制到基于标准产品构建的标准曲线上。通过电子病历中的数据收集表获得流行病学、临床和实验室特征以及治疗和结局数据，并分析临床数据与疾病严重程度之间的关系。结果共采集患者呼吸道、粪便、血清和尿液标本3497份，检测SARS冠状病毒2型RNA病毒载量。通过检测痰液和唾液样本确认所有患者感染。在55例（59%）患者的粪便和39例（41%）患者的血清中检测到RNA。一名患者的尿样对SARS-CoV-2呈阳性。粪便中病毒的中位持续时间（22天，四分位距17-31天）显著长于呼吸道（18天，13-29天; P=0.02）和血清样本（16天，11-21天; P<0.001）。重度疾病患者呼吸道样本中病毒的中位持续时间（21天，14-30天）显著长于轻度疾病患者（14天，10-21天; P=0.04）。在轻度组中，病毒载量在疾病发作后第二周达到峰值，而在重度组中，病毒载量在第三周期间继续保持高水平。年龄大于60岁的患者和男性患者的病毒持续时间较长。结论SARS-CoV-2在粪便标本中的持续时间明显长于呼吸道和血清标本，提示疫情防控中应加强粪便标本的管理，且病毒在重症患者呼吸道组织中的持续时间较长，载量较高，峰值出现较晚。
Abstract Objective To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China. Design Retrospective cohort study. Setting A designated hospital for patients with covid-19 in Zhejiang province, China. Participants 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020. Main outcome measures Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed. Results 3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients. Conclusion The duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.