Positive RT-PCR Test Results in Discharged COVID-19 Patients: Reinfection or Residual?

Background: The coronavirus disease-19 (COVID-19) is a highly infectious disease. Moreover, 14% of the discharged patients tested virus positive again. However, the underlying clinical mechanisms are still under investigation. Case presentation: The current study summarized the clinical course, radiological features and laboratory test results of two COVID-19 patients who tested positive again during the quarantine after hospital discharge. We found that while all symptoms were relieved, their lesions in lungs were not fully recovered, and both of them had slight coughs. In addition, when the lesions were further recovered and the cough symptoms were further remitted, they tested virus negative again. Conclusions: These results implied that the positive result is unlikely caused by the reinfection from others or the remained virus. Rather, it may derive from the remained virus transferred from the lower respiratory tract to the throat or nose with coughs. Accordingly, we proposed some suggestions regarding the discharge management. This study enhances our knowledge of the progress of COVID-19 and benefit the control of this disease.

discharging from the hospital [9][10]. According to Caixin magazine's report [10], approximately 14% of discharged patients in Guangdong province are readmitted after testing positive again. However, the clinical mechanisms underlying this phenomenon remain obscure.
Wenzhou, a city in the southeast of China, has the largest number of cases (504 to date) in China outside Hubei Province. The First Affiliated Hospital of Wenzhou Medical University, one of the designated hospitals for treating COVID-19, received two patients who tested positive again after hospital discharge. Here, we summarized the clinical course, radiological features and laboratory test results of these two patients. This study was approved by the ethical committee of the First Hospital Affiliated to Wenzhou Medical University and written informed consent was waived for this retrospective study.
was less than 0.499mg/L normal range, 0-8mg/L). On admission, non-enhanced chest computed tomography (CT) was performed ( Figure 1F), which showed multiple bilateral mixed pattern of ground-glass opacities and consolidation in lungs, including inferior lingual segment of left upper lobe, dorsal segment of left lower lobe, lateral basal segment of left lower lobe, lateral segment of right middle lobe, lateral basal segment of right lower lobe and posterior basal segment of right lower lobe. This patient tested positive RT-PCR nucleic acid 3 days after hospitalization. Note: *means the value abnormally decreased. #means the value abnormally increased.
After 13 days of treatment, including interferon inhalation, antiviral therapy of lopinaviritonavir tablets and symptomatic supportive care, the patient's symptoms were remitted and her body temperature became normal. At day 14, chest CT showed decreased ground-glass opacities ( Figure 1G). RT-PCR of the patient's pharyngeal swab became negative in two consecutive tests with one day interval combined with negative stool nucleic acid test. Eighteen days after the hospitalization, the patient met hospital discharge criteria and was discharged. According to the diagnosis and treatment of COVID-19 in China (trial sixth Edition), the criteria for hospital discharge are as follows: (1) normal body temperature lasts for longer than three days, (2) Figure 2G). On day 16, the patient met the discharge criteria and was discharged.

Follow-up
After hospital discharge, the two patients were quarantined. They were required to monitor their temperature and symptoms by themselves and return to hospital after one week, two weeks, and four weeks, respectively. Six days after the discharge, both of them were found virus positive again and were readmitted to the hospital. On readmission, they both had no fever but slight coughs, and none of them showed renewed symptoms.
Laboratory test results (Table 1)

Discussion And Conclusion
Since the patients were quarantined after hospital discharge, they were unlikely to be infected by others. Since the follow-up CT scans showed that the lesions were not fully recovered, it is reasonable to assume that these discharged patients might still carry the virus [13]. However, all the symptoms were remitted, which rule out the possibility of the Accordingly, it is suggested that the specimen detection of bronchoalveolar lavage fluid from the lower respiratory tract should be used as the discharge criteria. Meanwhile, since previous studies had reported false-negative RT-PCR nucleic acid test results [7,14], more consecutive nucleic acid tests for more tissues should be performed before discharge. We also suggest that the patients should not be discharged until their cough symptoms are largely recovered. We estimated that this may costed two weeks more quarantine time in the hospital. Even if the above suggestion cannot be fully adopted due to the limited health care resource, the discharged patients should wear masks and be retested one week, two weeks and four weeks, respectively after discharged, in order to reduce the risk of reinfection and further transmission. issues can be addressed with larger sample size and more case-control studies.
The current study described the clinical information and radiological features of two COVID-19 patients who tested positive again after hospital discharge. The results imply the progress trajectories of this disease. Therefore, we suggest that the hospital discharge criteria should be revised and the management of discharged patients should be strengthened. In summary, our study provides a better understanding of the progress of this disease, and provides some direction for future studies. It also benefits the public health by making policies accordingly.
corresponding author.

Competing Interests
The authors have declared that no competing interest exists.

Funding
This study was supported by Zhejiang Medical and Health Sciences and Technology Program (2019KY102) and Wenzhou Science and Technology Bureau Project (2018Y0144).