key: cord-317948-svgguadm
authors: Xiao, Ai Tang; Tong, Yi Xin; Zhang, Sheng
title: Profile of RT-PCR for SARS-CoV-2: a preliminary study from 56 COVID-19 patients
date: 2020-04-19
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa460
sha: 
doc_id: 317948
cord_uid: svgguadm

A novel coronavirus (COVID-19) pandemic threatens the world. Here, we first studied the dynamics profile of SARS-CoV-2 from 56 recovered COVID-19 patients. We found virus shedding was up to 6 weeks after onset of symptoms. Prolonged observation period is necessary for older patients.

To date, an outbreak of infectious diseases--coronavirus disease 2019 (COVID-19) associated with Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) continues in Wuhan, China and threatens countries such as Korea, Italy, Iraq and Japan, etc. [1] [2] Over 50 countries are fighting against the disease. As of March 4 th , 2020, more than 85,000 cases were diagnosed worldwide with a death rate around 2%.

Before this study, some studies reported cases of viral detection by RT-PCR at different timepoints throughout the disease course. [3] [4] [5] However, these reports monitored SARS-CoV-2 in the acute phase of infection. Currently no study reported the viral dynamics of SARS-CoV-2 infection in a long observation period. Understandings the profile of virus in patients' respiratory specimens can assist diagnosis and reflect the disease course. Therefore, we collected clinical specimens from 56 COVID-19 patients and reported the results of SARS-CoV-2 detection during the disease course. reading frame 1ab (ORF1ab) and nucleocapsid protein (N), were tested during the real-time RT-PCR assay. If two consecutive negative results were achieved, the period between symptoms onset and the date of first negative RT-PCR test result was defined as viral nucleic acid conversion time. All data (test dates and results of RT-PCR assay) were collected up to the final follow-up date (March 3 rd , 2020).

A total of 56 patients diagnosed as COVID-19 were included in this study. According to the guideline, all included patients were mild to moderate [7] . No patient was transferred to ICU. The median age was 55 years (interquartile range, IQR, 42-68; range, 25-83), comprising 34 (60.7%) men and 22 (39.3%) women. At the end of follow-up, all patients recovered and were discharged from hospital.

The total number of SARS-CoV-2 RT-PCR assay from 56 patients was 299, with 5 tests per patient.

The longest duration between RT-PCR test for SARS-CoV-2 was 42 days after onset of symptoms. The median duration between onset of symptom to nucleic acid conversion was 24 days (IQR, 18-31). The details of demographic characteristics and RT-PCR test results were shown in supplemental Table 1 .

The number of positive and negative results of RT-PCR tests were shown in Figure 1A . In first 3 weeks after symptoms onset, majority results of RT-PCR for SARS-CoV-2 were positive. From week 3 after symptoms onset, number of negative RT-PCR results increased. All results of RT-PCR tests were negative in week 6 after onset. (Supplemental Table 2 ) The positive rate of RT-PCR test results was highest at week 1 (100%), followed by 89.3%, 66.1%, 32.1%, 5.4% and 0% at week 2, week 3, week 4, week 5 and week 6 respectively. (Figure 1B) We divided patients into non-prolonged and prolonged shedding group according to nucleic acid conversion time (≤24 days or >24 days). As shown in supplemental table 3, patients with prolonged viral shedding tend to be older (p=0.011) and were more likely to have comorbidities as diabetes (p=0.016) and hypertension (p=0.006). test results kept declining in 6 weeks. (Figure 1) The above findings suggested that SARS-CoV-2 viral replication has a relatively long period in infected patients.

Our study attempted to explore the correlation between clinical characteristics and viral shedding in COVID-19 patients. We found that patients with prolonged viral nucleic acid conversion tend to be older and with more comorbidities. Previous studies suggested that coronavirus is more likely to infect older individuals, for whom the immunopathogenesis and induction of a proinflammatory cytokine storm might be the culprit. [12] Older patients with impaired immune function might have a prolonged period of viral elimination. 6 As a result of errors in sampling and testing, false negative result of RT-PCR for SARS-CoV-2 is very common in clinical settings. Meanwhile, it is recommended by the current diagnosis and treatment guideline for SARS-CoV-2 from Chinese National Health Committee that the criteria to discharge a patient included the relief of symptoms, improvement in radiography and two consecutive negative RT-PCR results for SARS-CoV-2. [7] In our study we found two consecutive negative RT-PCR test results followed by a positive result in 4 patients (patient number 20, 24, 37 and 56). Evidence suggested that the outbreaks of COVID-19 may be correlated to its rapid person-toperson transmission ability. [2] Since specific treatment had not been validated for COVID-19, traditional public health tactics-isolation, quarantine and community containment are critical to control the spread. [14] [15] [16] This preliminary study has found evidence of the dynamic profile of SARS-CoV-2 in non-ICU COVID-19 patients during disease course. According to the results in our study, we suggested prolonged observation and repeat confirmation of RT-PCR test from respiratory specimens for safe discharges and discontinuation of quarantine.

All authors participated in the study design. ATX and SZ conceived the study, analyzed the data and drafted the manuscript. YXT helped critically revise the manuscript and collected data. All authors have agreed on the final version and meet the major criteria recommended by the ICMJE 12 Figure 1 

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We thank Ms. Cheng Chen for English grammatic correction of this manuscript. This study was approved by the Ethics committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. All procedures followed in this study were in accordance with the 1964 Helsinki Declaration and later versions. Oral consent was obtained from patients involved before enrollment when data were collected retrospectively. The database used and/or analyzed during the current study is not publicly available (to maintain privacy) but can be available from the corresponding author on reasonable request.

Funding No funding resources to declare for this study.

All authors declare that there are no conflicts of interest.8