Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study

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.

Fig 1

Duration of detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by sample types and disease severity. Coloured bars represent medians and black bars represent interquartile ranges

Fig 2

Comparison of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load by sample types and disease severity. Coloured bars represent medians and black bars represent interquartile ranges

Fig 3

Smooth lines were fitted using loess method to explore the variation of viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the days since symptoms onset in respiratory samples from patients with mild and severe disease and in stool samples

Fig 4

Association between sex and age and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Coloured bars represent medians and black bars represent interquartile ranges