key: cord-0854259-bi3bl5qt authors: Zhou, Rui; Li, Furong; Chen, Fengjuan; Liu, Huamin; Zheng, Jiazhen; Lei, Chunliang; Wu, Xianbo title: Viral dynamics in asymptomatic patients with COVID-19 date: 2020-05-11 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2020.05.030 sha: d24066fe17fed6ea2bd67d6e06307ef8947f1fd1 doc_id: 854259 cord_uid: bi3bl5qt Abstract Data are limited on the viral load, viral shedding patterns and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). We included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in incubation period (APIs); the other 9 patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The cycle threshold (Ct) values of APs (39.0, IQR 37.5-39.5) was significantly higher than those of APIs (34.5, IQR 32.2-37.0), which indicated a lower viral load in APs, but the duration of viral shedding remained similar between the two groups (7 days IQR 5-14 vs. 8 days IQR 5-16). The study findings demonstrated that although they have a lower viral load, APs with COVID-19 still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid tests are warranted. APIs, n=14 Graphical Abstract (for review) 1. The viral load and viral shedding patterns of asymptomatic patients with COVID-19 were described. 2. The viral load of asymptomatic patients peaked during the early stage of hospitalization. 3. The cycle threshold (Ct) values of those who remained asymptomatic during hospitalization were higher than those who presented symptoms after admission. shedding, which suggested the possibility of transmission during the asymptomatic period. Rui Zhou a,1 , Furong Li a,1 , Fengjuan Chen b,1 , Huamin Liu a , Jiazhen Zheng a , Chunliang Lei b,* , Xianbo Table S1 ). All patients underwent chest computed tomography (CT) scans on admission and were followed up every three days or as necessary. Four (44.44%) APs and 9 (41.93%) APIs showed bilateral abnormalities typical of pneumonia. Of the APIs, 6 (27.27%) showed radiographic progression 8 days (IQR 7-9) after admission, but all exhibited improvement before discharge (Figure 1) . Five APs and 14 APIs who had positive RNA tests during hospitalization had available Ct values. The median viral load during hospitalization in APs (39.0, IQR 37.5-39.5) was significantly lower than that in APIs (34.5, IQR 32.2-37.0). To evaluate the viral dynamics of asymptomatic cases of COVID-19, we further stratified these data according to length of hospital stay (LOS) at the time of sampling. The median Ct values of APs were consistently higher during hospitalization than those of APIs (Figure 2A) . The viral load of APs peaked during the first week after admission, while that of APIs peaked during the second week. We also studied serial samples from five APs and 14 APIs ( Figure 2B ). All APs tested negative for SARS-CoV-2 RNA within two weeks after admission, while APIs tended to have a longer viral shedding duration, though no significant difference was found. Among APs, those who never experienced pulmonary symptoms and tested negative for SARS-CoV-2 RNA later should be regarded as having subclinical infections. Other patients may not have shown subjective signs but they developed pulmonary symptoms including ground glass opacity or subsegmental areas of consolidation, and these patients were considered to be in the period of illness. J o u r n a l P r e -p r o o f 5 The 22 patients who developed symptoms after admission were considered to be asymptomatic patients who were in the incubation period, which is the time from virus vector exposure to the appearance of disease symptoms and signs. We noted that the viral load of APs peaked during the early stage of hospitalization, which was different from the results observed in patients with Severe Acute Respiratory Syndrome (SARS) in 2003 (Peiris et al. 2003) , while those of APIs peaked during the second week as symptoms appeared. The phenomenon in which APs have a lower viral load than APIs has also been observed for the Influenza virus. However, the duration of viral shedding of APs and APIs was similar, which reflected the potential of APs to transmit the virus to communities (Ip et al. 2016) . Overall, our study demonstrated that even though these patients may be asymptomatic, they still have a certain period of viral shedding, which suggested the possibility of transmission during the asymptomatic period. These asymptomatic cases of COVID-19 could be an important source of the contagion that need to be controlled by longitudinal surveillance via virus nucleic acid tests. Further studies are needed to investigate and quantify the contribution of persons with asymptomatic COVID-19 infections to COVID-19 transmission. This research was supported by Open Project of Guangdong Provincial Key Laboratory of Tropical Disease Research. The funding source had no role in the design, execution, analysis, interpretation of data, or decision to submit the results of this study. The study was approved by the institutional ethics board of Guangzhou Eighth People's Hospital and the requirement for informed consent was waived by the ethics board. APs: patient 1-9; APIs: patient 10-31 Abbreviations: AP, asymptomatic patient; API, asymptomatic patient in incubation period. Presumed Asymptomatic Carrier Transmission of COVID-19 Covid-19: four fifths of cases are asymptomatic, China figures indicate Viral Shedding and Transmission Potential of Asymptomatic and Paucisymptomatic Influenza Virus Infections in the Community National Institute for Viral Disease Control and Prevention (China) Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: A prospective study Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases We acknowledge the patients, staffs at Guangzhou Eighth People's Hospital and staffs at the Control and Prevention for their input and collaboration on this research.