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Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study.
BMJ. 2020 04 21; 369:m1443.BMJ

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.

Authors+Show Affiliations

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Department of Pharmacy, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Bone Marrow Transplantation Centre, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Department of Respiratory Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Department of Critical Care Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.Department of Critical Care Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Centre for Infectious Diseases, Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China. Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China liangtingbo@zju.edu.cn. Zhejiang Provincial Key Laboratory of Pancreatic Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. The Innovation Centre for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32317267

Citation

Zheng, Shufa, et al. "Viral Load Dynamics and Disease Severity in Patients Infected With SARS-CoV-2 in Zhejiang Province, China, January-March 2020: Retrospective Cohort Study." BMJ (Clinical Research Ed.), vol. 369, 2020, pp. m1443.
Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ. 2020;369:m1443.
Zheng, S., Fan, J., Yu, F., Feng, B., Lou, B., Zou, Q., Xie, G., Lin, S., Wang, R., Yang, X., Chen, W., Wang, Q., Zhang, D., Liu, Y., Gong, R., Ma, Z., Lu, S., Xiao, Y., Gu, Y., ... Liang, T. (2020). Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ (Clinical Research Ed.), 369, m1443. https://doi.org/10.1136/bmj.m1443
Zheng S, et al. Viral Load Dynamics and Disease Severity in Patients Infected With SARS-CoV-2 in Zhejiang Province, China, January-March 2020: Retrospective Cohort Study. BMJ. 2020 04 21;369:m1443. PubMed PMID: 32317267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. AU - Zheng,Shufa, AU - Fan,Jian, AU - Yu,Fei, AU - Feng,Baihuan, AU - Lou,Bin, AU - Zou,Qianda, AU - Xie,Guoliang, AU - Lin,Sha, AU - Wang,Ruonan, AU - Yang,Xianzhi, AU - Chen,Weizhen, AU - Wang,Qi, AU - Zhang,Dan, AU - Liu,Yanchao, AU - Gong,Renjie, AU - Ma,Zhaohui, AU - Lu,Siming, AU - Xiao,Yanyan, AU - Gu,Yaxi, AU - Zhang,Jinming, AU - Yao,Hangping, AU - Xu,Kaijin, AU - Lu,Xiaoyang, AU - Wei,Guoqing, AU - Zhou,Jianying, AU - Fang,Qiang, AU - Cai,Hongliu, AU - Qiu,Yunqing, AU - Sheng,Jifang, AU - Chen,Yu, AU - Liang,Tingbo, Y1 - 2020/04/21/ PY - 2020/4/23/entrez PY - 2020/4/23/pubmed PY - 2020/4/25/medline SP - m1443 EP - m1443 JF - BMJ (Clinical research ed.) JO - BMJ VL - 369 N2 - 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. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/32317267/full_citation L2 - https://www.bmj.com/lookup/pmidlookup?view=long&amp;pmid=32317267 DB - PRIME DP - Unbound Medicine ER -