This is a descriptive case series of 51 COVID-19 patients after obtained two sequential negative nucleic acid testing results. It presents the clinical and CT imaging features when COVID-19 cases turn to negative in nucleic acid detection tests. The clinical data continue return to normal, and nearly half of the moderate patients with CT ground-glass absorption reduced less than 60% within one week, which might need further attention. In addition, fecal positive for SARS-CoV-2 is common among this group of cases.
Since December 2019, COVID-19 first occurred in Wuhan [17, 18]. China, this disease had rapidly spread from Wuhan to other areas and worldwide. The rapid escalation in the number of COVID-19 cases has resulted in an insufficiency of health-care resources [19]. To improve the availability and accessibility of health-care resource in China, the Chinese government had issued policies and criteria for the diagnosis and treatment of COVID-19. In Shenzhen, China, all suspected and confirmed cases were sent to the government assigned hospital for diagnosis and initial treatment, and patients that reached discharge criteria but still had clinical symptoms would be transferred to other hospital for further treatment, which helped to improve quality of medical services and make a better use of medical resources. However, the effectiveness and the usefulness of this further treatment for COVID-19 remain unclear.
In our study, the most common symptoms by the time of diagnosis were fever and cough, which was similar with previous studies [12]. In a meta-analysis with a total of 61 studies (59,254 patients) [12], the most common disease-related symptoms were fever (82%, 95% confidence interval (CI) 56%-99%) and cough (61%, 95% CI 39%-81%). Compared with mild cases, moderate cases had higher proportion of comorbidities. After negative in nucleic acid detection tests, no cases suffered fever and the proportion of cough also decreased significantly (60.8% vs. 33.3%), indicating that the initial symptomatic treatments were effective. However, the proportions of other symptoms such as sore throat, nasal congestion and runny nose, and dyspnea were generally the same, but the non-specific symptoms were observed.
In our study, left lower lobe was most commonly affected, and right lower lobe was second common location of lesions. This finding is consistent with the previous radiological studies of patients with COVID-19 infection [20, 21]. Generally, lower lobes are commonly affected due to the anatomical structure of the trachea and bronchi: the right bronchus is short and straight. By the time patients transferred to our hospital, the most common CT imaging manifestations were ground-glass density shadow only and strip-like density shadow. Serial CT imaging of patients helped to continuously monitor disease changes.
At the end of the first week, lesion range reduced over 50% than that of the baseline among 7/12 patients. However, there were still half of the patients with abnormal imaging, and 4 cases with absorption were less than 5% within one week. The phenomenon suggested that, even after the negative for throat swab nuclear acids test, the virus might be still existed in the human body, but under the detection threshold level of throat swab test [22]. Study has showed that chest CT was more sensitive than RT-PCR [23]. Further repeated tests for this group of patients, even with negative for throat swab, positive results for fecal tests were observed in same of the patients, which mean that the virus might be not completely eliminated and still be a risk of transmission. Though the clinical features of the participants continued return to normal after negative throat swab nuclear acids test with treatment, the imaging features still abnormal and further isolation and treatment for patients after the negative for throat swab nuclear acids test is necessary. Studies has indicated that if patients had clinical symptoms, epidemiological characteristics, and chest CT imaging characteristics of viral pneumonia that were compatible with COVID-19 infection, careful consideration of the isolation and treatment of these patients is still needed even if the RT-PCR test is negative [24].
In one case (case 17), the ground-glass with absorption < 5% lasted for almost one month. Considering the asymptomatic persistently and negative for nuclear acids, we speculated that this abnormal imaging might cause by old lesions due to other respiratory diseases.
There were also several limitations in the present study. First, the COVID-19 cases were confirmed through nucleic acid tests using respiratory tract specimens. After these patients obtained two sequential negative respiratory tract sample results, part of they were transferred to our hospital for further treatment till the clinical symptoms were mostly improved. For some patients with fecal test were still positive. However, our study reported these patients’ the clinical characteristics and its dynamic changes during hospitalization, which could be a supplement to the current evidence of 2019-nCoV. Second, given the small sample size, it is difficult to systematically explore the differences between mild case and moderate case, and the type I error should take into account. Moreover, the analyses have not been adjusted for multiple comparisons, the findings should be interpreted as exploratory and descriptive. Third, among the 51 cases, given the requirements of patients, the treatment including drug and traditional Chinese medicine, and this could be an important confounder for comparison. Finally, for retrospective study design, some of the data were not collected or measured. For example, only less than half of the patients with repeated clinical measurements.