key: cord-0011581-ii3a6ne7
authors: Zhao, Fang; Yang, Yang; Wang, Zhaoqin; Li, Liang; Liu, Lei; Liu, Yingxia
title: The Time Sequences of Oral and Fecal Viral Shedding of Coronavirus Disease 2019 (COVID-19) Patients
date: 2020-05-16
journal: Gastroenterology
DOI: 10.1053/j.gastro.2020.05.035
sha: df8bc77bd42aa3d2be38a85659411dc8149c6a1b
doc_id: 11581
cord_uid: ii3a6ne7

nan

contributed to the data analysis. FZ, YY, YL, LLi and LL contributed to the manuscript preparation. All the authors have read and approved the manuscript. 

Recent studies found that SARS-CoV-2 could be detected in the fecal samples, and live virus could be successfully isolated from stool and used for successful infection in cell cultures, indicating a possible fecal-oral transmission [1] [2] [3] . Although important for the disease management, information on the time sequences of oral and fecal viral shedding of Coronavirus Disease 2019 (COVID-19) patients needs more investigation 1, 4 . In this study, we tested in 401 COVID-19 patients for viral RNAs in both respiratory and rectal specimens, and tracked for more than 7 weeks to present a clear elucidation of the oral and fecal viral shedding profile, such as the duration, viral load, and relationship to patient symptoms. Table S2) . The overall coincidence rate of respiratory and rectal samples was 70.6%, and gradually increased during the disease progression (Table S2) . 11 (61.54%), 9 (56.25%), 9 (64.29%), 4 (51.14%), 3 (50%) and 2 (100%) pairs with higher viral loads in rectal than respiratory samples were found in 1~6 W.A.O, respectively ( Figure 1B ).

Patients positive for fecal viral RNA were divided into two groups according to the durations of fecal viral shedding, including >4 weeks group and ≤ 4 weeks group.

Using multivariate logistic regression model, we found that both the neutrophil levels and the intervals between antiviral treatment and illness onset were independently associated with the duration of fecal viral shedding. The odds ratios for the neutrophil levels and intervals between antiviral treatment and illness onset were 1.549 (95% CI:

1.055-2.405; p=0.034) and 1.168 (95% CI: 1.011-2.369, p=0.042), respectively.

Transmission routine varies in different viral infections, and elucidation of the viral shedding profile is crucial for the diagnosis, treatment and control of COVID-19.

Positive rate of fecal SARS-CoV-2 RNA in children (<18 years) was significantly higher than adults. The SARS-CoV-2 has a strong transmission capacity in children, but the clinical presentation of COVID-19 was generally milder in children than adults 6, 7 . Therefore, viral diagnosis in stool specimens is crucial in the diagnosis and Notably, we found that SARS-CoV-2 RNA in fecal samples remained for an unexpected long period, with higher positive rate and higher viral load than the paired respiratory samples. The longest duration observed was 43 days, much longer than the usual 3-5 weeks from symptom onset to discharge for most patients 4 , suggesting that SARS-CoV-2 test of rectal swabs is crucial to minimize false negatives for the laboratory diagnosis of COVID-19, and to reduce the potential fecal-oral transmission from asymptomatic COVID-19 patients. An obvious difference in the interval from illness onset to antiviral therapy was observed, raising the possibility that early 7 antiviral treatment might reduce SARS-CoV-2 persistence within the intestinal tract.

Our study provides a comprehensive respiratory and fecal viral shedding profile of a large COVID-19 patient cohort with the longest tracking duration to our knowledge.

The gastrointestinal viral reservoir is potentially a long-lasting fomite for SARS-CoV-2 transmission even for asymptomatic patients. were considered putatively positive. Samples whose Ct was higher than 37 were re-tested and considered positive if Ct was ≥ 37 but ≤ 40 and negative if viral RNAs were undetectable on the second test.

Categorical variables were described as frequency rates and percentages. Continuous variables were described as mean and standard deviation or median and interquartile range (IQR) values. Means for continuous variables were compared using independent group t-tests when the data were normally distributed; otherwise, the Mann-Whitney U test was performed. Comparisons of categorical variables were done using the Chi-Square test, whereas the Fisher exact test was used when the data were limited. The pairwise comparison between groups was performed and Bonferroni Correction was applied to correct for multiple comparisons. To explore factors associated with the positive detection of viral RNA in stool and the clearance time of fecal virus RNA > 4 weeks, we used a multivariable logistic regression model.

A two-sided α of less than 0.05 was considered statistically significant. All statistical analysis was done using R version 3.6.2.

Supplementary Table 1 

National Health Commission of China

O: weeks after illness onset

R: rectal swab; N: nasal swab

+): positive; (-): negative

The authors appreciated the support from Dr. Chuming Chen, Ling Qing, and Xiaohe Li (Shenzhen Third People's Hospital) on patient sample collection, and Dr. Quanying Liu, Zhichao Liang, and Haihui Wang (Southern University of Science and Technology) on data analysis.