In the present study, we evaluated the time correlation between serial RT-PCR results and serial chest CT findings and investigated lung imaging changes of COVID-19 pneumonia by the time. The major findings of the study were twofold: first, the time of initial chest CT abnormality was significantly shorter than that of initial RT-PCR positive result, the time of lung CT improvement shorter than that of RT-PCR conversion to negative; second, chest CT is a reliable, non-invasive, rapid tool to monitor the occurrence, deterioration and improvement of COVID-19 pneumonia.
The confirmation of COVID-19 infection was dependent on viral nucleic acid test by RT-PCR assay, which determined the patient hospitalization or quarantine home. But RT-PCR test had its distinct limitations due to its low sensitivity, insufficient stability, and relatively long processing time to get the results. Some scholars reported the positive rate of RT-PCR assay for throat swab samples was 30-60% (15, 16). A lot of factors can affect the RT-PCR results, including sampling operations, specimens source (upper or lower respiratory tract), sampling timing, and performance of detection kids (16). The recent study showed salivary viral load was highest during the first week after symptom onset (17), which could account for the fast spreading nature of this pandemic at the early stage. Those patients without timely isolation and therapy due to initial negative RT-PCR results, would definitely promote COVID-19 to spread.
Chest CT is a non-invasive, rapid, convenient imaging diagnostic tool and can detect mild lung abnormality at the early stage of COVID-19 pneumonia. Our study showed the time of initial chest CT abnormality (3.23±3.04 days) was significantly shorter than that of initial RT-PCR positive result (5.84±3.23 days). Therefore, CT plays a vital role in the early detection of COVID-19 pneumonia, especially for the patient with initial negative RT-PCR results. Of course, the specificity of CT in diagnosing COVID-19 pneumonia is low in spite of its high sensitivity. T.A et al (15) reported the sensitivity and specificity of chest CT in indicating COVID-19 infection were 97% and 25%, respectively. Although RT-PCR test is the gold standard for the diagnosis of COVID-19 infection, chest CT examination is essential for the early identification of the potential patients and helps determine the next measure. The COVID-19 infection has been currently upgraded from epidemic to pandemic disease by the World Health Organization (WHO) (18), chest CT will certainly play a crucial role in the early detection of the disease and contain the pandemic spread.
Our study also found the time of lung CT improvement (11.58±4.59 days) was significantly shorter than that of RT-PCR conversion to negative (14.38±5.78 days). This indicates CT is very useful to monitor the course of COVID-19 pneumonia and direct the clinician to adjust the therapeutic strategy.
In our study, dynamic serial chest CT examination (4-6 times) with relatively big patient population provided us reliable data to observe the disease course. We divided the disease into 3 stages according to the time since the onset of the initial symptoms. At the early stage, CT features of COVID-19 are predominantly GGO and small vessel thickening. GGO is the main CT feature, and small vessel thickening is the secondary feature. With the disease progression, GGO evolves to consolidation. In the process of progression, crazy paving sign is also markedly enhanced. At stage 2, air bronchogram sign is also dramatically increased as secondary sign of consolidation. Small vessel thickening is still abundant as the secondary sign of GGO and consolidation. We also noticed fibrotic lesions were gradually added, which represents reparative process. At stage 3, a prominent feature lay in fibrotic lesions significantly increased, accompanying more consolidation, GGO and crazy paving sign. This indicates reparative and progressive process of COVID-19 pneumonia simultaneously and various CT features coexist at stage 3. Our study demonstrated the time of lung improvement was 11.58±4.59 days. The lung CT appearance may be consistent with the pathology. The autopsy and histological examination of COVID-19 pneumonia showed bilateral diffuse alveolar damage with proteinaceous exudate, cellular fibromyxoid exudate, pulmonary edema, reactive hyperplasia of pneumocytes, desquamation of pneumocyte, hyaline membrane formation, fibroblastic plugs in airspaces and interstitial mononuclear inflammatory infiltration (19, 20), which may be accord with the appearance of GGO, consolidation and crazy paving sign. Tian et al pointed out patchy pneumocyte hyperplasia and interstitial thickening indicating an ongoing reparative process at the early stage of COVID-19 pneumonia (20). Notably, when the patients met the discharge criteria, there was still patchy consolidation left in the lung. Could this explain that RT-PCR test converted to positive again for the individual cases after leaving hospital? A larger-scale investigation is required for a full validation. Anyway, this phenomenon suggests that the arrangement is reasonable for patients quarantining home for another period (two weeks in China) after discharge.
Our study also showed typical COVID-19 pneumonia started as unilateral of bilateral sub-pleural GGO, then evolved to consolidation, which involved sub-pleural and central areas. Our study also found 12.9% patients showed normal chest CT images at the early stage. Then the number of involved lung lobes was increased at the stage 2. However, the number of involved lung lobes was still more at the stage 3 and had no significant difference compared to that of stage 2. Residual GGO, scattered consolidation and sub-pleural parenchymal bands still existed at the stage 3. So the patients still need to be followed up after hospital discharge.
There are several limitations in the present study. First, this is a retrospective study in a short time, and long term radiological follow up is needed to supervise the pulmonary outcome due to the novel coronavirus infection. Second, this study lacks of more severe COVID-19 pneumonia patients (including respiratory failure needing mechanical ventilation, shock, multiple organ failure needing ICU care) (4), so for those patients the changes of CT findings need to be investigated in next study. Third, the radiation dose of CT scans was not evaluated, but it is more important to detect the infected patients, understand the disease course, manage the patients and contain the pandemic.
In conclusion, chest CT is playing a vital role in the early detection of COVID-19 pneumonia, monitoring lesion progression and improvement. It is earlier to show lung abnormality than the time of initial positive nucleic acid test with RT-PCR in the detection of COVID-19 infection. It is also earlier to demonstrate lung improvement than the time of RT-PCR conversion to negative. Chest CT should be considered as a screening of COVID-19, especially under circumstance of pandemic worldwide.