The present study describes the clinical characteristics of 33 COVID-19 patients with recurrent PCR positivity after discharge. Most of these patients were asymptomatic during the duration of the recurrent RNA positivity. These asymptomatic carriers brought more challenges to the identification and control of the COVID-19 epidemic worldwide.
In the present study, some patients presented with mild nonspecific symptoms, including cough, fatigue, sore throat, fever and expectoration. In other reports, merely 32% of patients had mild cough during the duration of the recurrent RNA positivity. Furthermore, many cases reported that the clinical symptoms of COVID-19 patients with recurrent PCR positivity did not aggravate.[7, 10] However, there has been no reports on the infectious capacity of COVID-19 patients with recurrent PCR positivity. Therefore, it remains difficult to identify and control such patients through clinical symptoms. In order to avoid such patients from becoming a potential source of infection again, all discharged patients should be quarantined and regularly tested for infectivity assessment by rechecking the PCR.
The median duration of recurrent RNA positivity was 9.0 days. Furthermore, it was found that serum SARS-CoV-2-specific IgG antibody titer, serum creatinine level and female gender were risk factors for the prolonged duration of recurrent RNA positivity. The duration of positive RT-PCR persistence was associated with antibody response and clinical manifestations. Patients with symptoms and the development of anti-SARS-CoV-2 IgM antibodies had a shorter duration of positive RT-PCR results, and had no worsening clinical conditions, when compared to patients without the presence of anti-SARS-CoV-2 IgM antibodies. Specific IgG antibodies are important for protecting the host from infection by blocking viral entry into host cells after viral infection. The median duration of IgG was detected at 14 days (IQR, 10–18) after symptom onset, with a positive rate of 77.9%. There was no association between plateau IgG levels and the clinical characteristics of patients. According to the report of Kaijin Xu, male gender was an independent risk factor for prolonged viral RNA shedding in COVID-19 patients. In the present study, female patients presented with a longer duration of recurrent RNA positivity. Histopathological studies have provided direct evidence of the invasion of SARS-CoV-2 into kidney tissues. Cheng Y et al. reported that elevated baseline serum creatinine was an independent risk factors for in-hospital death. However, there has been no report on the relationship between serum creatinine level and the duration of recurrent RNA positivity. Hence, the influence factor on the duration of recurrent RNA positivity needs further studies.
The cause for the recurrent positive viral RNA test after discharge in COVID-19 patients remains unclear. The deficiency of cellular immune function may lead to the incomplete shedding of the virus, resulting to the occurrence of "recurrence". Yao X et al. reported a case with negative detection of SARS-CoV-2 virus nucleic acid from nasopharyngeal swabs. However, the autopsy revealed residual SARS-CoV-2 in the lungs. These results highlight the remaining of SARS-CoV-2 in the lungs of discharged COVID-19 patients. Comorbidity and therapeutic drugs, such as antiviral drugs and glucocorticoids, may also affect virus shedding. After becoming infected with the virus, the human body responds with specific antibodies production to avoid reinfection of the virus. If SARS-CoV-2 mutates within a short period of time, similar to hepatitis C virus, the patient may be infected again. The possibility of reinfection is unknown.
Two consecutive negative RNA tests is recognized as one of the discharge criteria.  According to the report of Wu et al., the positive rate of the SARS-CoV-2 RT-PCT test of nasopharyngeal swab, sputum, blood, feces and anal swabs is 38.13%, 48.68%, 3.03%, 9.83% and 10.00%, respectively. Xiao et al. reported that 21.4% of patients presented with a positive virus RNA test again after two consecutive negative tests. It has been speculated that these patients may have experienced a false negative RT-PCR result or prolonged viral clearance, rather than a “turn positive” or “recurrence”. However, the clinical characteristics and subgroup analysis was not performed for these patients. Hence, the false negative RT-PCR result or prolonged viral clearance may be the cause for these patients to turn from negative to positive after discharge. It has been suggested that performing more viral RNA tests, combined with clinical improvements, could avoid false negative and reduce the recurrence.
In order to prevent the missed diagnosis of discharged patients, whose PCR assays turned positive, the following suggestions are given: (1) Both nasopharyngeal and oropharyngeal swabs test for SARS-CoV-2 RNA should be performed to reduce the false-negative rate. Furthermore, more tests, more specimens, and more methods should be considered. (2) Patients in convalescence should also be regularly tested for infectivity assessment, and all discharged patients should be home quarantined for at least 14 days. (3) Some laboratory examinations, such as serum creatinine level, SARS-CoV-2-specific antibody titer, D-dimer, lymphocyte count and platelet count, should be combined with the RT-PCR negative test as an additional measure, in order to ensure that the infected patient has completely recovered, and can be released from quarantine.[10, 23]
The present study had several limitations. First, merely 33 discharged patients were included. Collecting data from a larger cohort would provide a more comprehensive understanding of these discharged patients. Second, the present study lacks a control group of COVID-19 patients discharged at the same time. Furthermore, even if anti-virus medicine was used for these readmitted patients, it was difficult to assess its effect on virus clearance. The etiological mechanism of COVID-19 patients with recurrent PCR positivity after hospital discharge should also be investigated.