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Research

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 doi: https://doi.org/10.1136/bmj.m1443 (Published 21 April 2020) Cite this as: BMJ 2020;369:m1443

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  1. Shufa Zheng, assistant research fellow1234,
  2. Jian Fan, associate research fellow234,
  3. Fei Yu, assistant research fellow234,
  4. Baihuan Feng, assistant research fellow234,
  5. Bin Lou, associate research fellow234,
  6. Qianda Zou, assistant research fellow234,
  7. Guoliang Xie, molecular biologist234,
  8. Sha Lin, assistant research fellow23,
  9. Ruonan Wang, assistant research fellow23,
  10. Xianzhi Yang, assistant research fellow23,
  11. Weizhen Chen, assistant research fellow234,
  12. Qi Wang, assistant research fellow234,
  13. Dan Zhang, assistant research fellow234,
  14. Yanchao Liu, assistant research fellow23,
  15. Renjie Gong, assistant research fellow23,
  16. Zhaohui Ma, assistant research fellow23,
  17. Siming Lu, assistant research fellow23,
  18. Yanyan Xiao, assistant research fellow23,
  19. Yaxi Gu, assistant research fellow23,
  20. Jinming Zhang, assistant research fellow23,
  21. Hangping Yao, professor1,
  22. Kaijin Xu, infectious disease physician1,
  23. Xiaoyang Lu, professor5,
  24. Guoqing Wei, professor6,
  25. Jianying Zhou, respiratory physician7,
  26. Qiang Fang, critical care physician8,
  27. Hongliu Cai, critical care physician8,
  28. Yunqing Qiu, professor1,
  29. Jifang Sheng, professor1,
  30. Yu Chen, professor1234,
  31. Tingbo Liang, professor91011
  1. 1State 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
  2. 2Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
  3. 3Centre of Clinical Laboratory, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  4. 4Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China
  5. 5Department of Pharmacy, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  6. 6Bone Marrow Transplantation Centre, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  7. 7Department of Respiratory Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  8. 8Department of Critical Care Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  9. 9Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  10. 10Zhejiang Provincial Key Laboratory of Pancreatic Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
  11. 11The Innovation Centre for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China
  1. Correspondence to: T Liang, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China liangtingbo{at}zju.edu.cn
  • Accepted 6 April 2020

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.

Footnotes

  • Contributors: TL and YC contributed equally to this paper and are joint corresponding authors. SZ, JF, FY, and BF are joint first authors. The corresponding and first authors conceived and designed the study. All authors selected the articles and extracted data. TL and YC were co-principal investigators. They designed and supervised the study and wrote the grant application (assisted by SZ). KX, XL, GW, JZ, QF, HC, YQ, and JS had roles in recruitment, data collection, and clinical management. SZ, JF, FY, BF, BL, QZ, GX, SL, RW, XY, WC, QW, DZ, YL, RG, ZM, SL, YX, YG, JZ, and HY did clinical laboratory testing and analysis. SZ, FY, BF, YC, and TL drafted the manuscript. All authors reviewed and revised the manuscript and approved the final version. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. TL and YC are the guarantors.

  • Funding: This work was supported by the China National Mega-Projects for Infectious Diseases (grant Nos 2017ZX10103008 and 2018ZX10101001) and the National Natural Science Foundation of China (grant Nos 81672014 and 81702079). The research was designed, conducted, analysed, and interpreted by the authors entirely independently of the funding sources.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the China National Mega-Projects for Infectious Diseases and the National Natural Science Foundation of China, for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethics committee of the First Affiliated Hospital, Zhejiang University School of Medicine (2020IIT A0107).

  • Patient consent: Obtained.

  • Data sharing: No additional data available.

  • The lead authors and manuscript’s guarantors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

  • Dissemination to participants and related patient and public communities: No study participants were involved in the preparation of this article. The results of the article will be summarised in media press releases from the Zhejiang University and presented at relevant conferences.

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