Discussion
As reported, patients with COVID-19 usually develop clinical symptoms after an incubation period of 4.1–7.0 days [11]. After admission, chest imaging examination was performed on them. According to the results of changes in this disease in recent studies [10, 11], the patient’s condition progressively worsens on the 3–5 days after symptom onset, and the guidelines for an imaging diagnosis of COVID-19 recommend that reviewing CT or plain radiograph is needed for suspected cases 3–5 days after diagnosis to observe changes in the disease status [12]. Thus, we assigned patients to two groups according to the time of onset of symptoms to analyze the CT findings in early-stage and progressive-stage of COVID-19. In this study, 62 confirmed patients with COVID-19 underwent chest CT scans, and positive rate of detecting the pulmonary parenchymal abnormalities was 100%. In addition, the CT data in our study were obtained from the initial chest CT examination of patients who had not received any antiviral therapy; these results may better reflect the degree of viral infection and the immune system status before clinical intervention and provide an important basis for clinical classification, treatment strategy development, and prognosis prediction.
In our study, the major characteristic of COVID-19 was GGO (61.3%), followed by GGO with consolidation (35.5%), rounded opacity (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). In contrast, pulmonary fibrosis (1.6%) and pleural effusions (3.2%) were rare on chest CT images. These various CT findings are likely related to the complex pathological changes in the lungs of patients with COVID-19. Although pathological changes in the lung tissue of COVID-19 patients have not yet been studied, recent studies have reported that SARS-CoV-2 is closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)–like coronaviruses, with approximately 79% homology with SARS-CoV and approximately 50% homology with MERS-CoV [17, 18]. Because the pathogenesis of viral infections in the same family may be similar, previous studies on coronaviruses may be helpful in understanding the various CT findings in COVID-19 patients based on similar pathological changes. In SARS patients, pathological changes include injury to pulmonary epithelial cells, hyaline membrane formation on in the inner wall of the alveoli, and a large number of tissue cells and mass thrombi formed by proliferative fibrous tissue that block the small airway and air cavity [19]. These pathological changes may be the main pathological basis of the CT findings, especially the GGO.
Among all the CT findings, GGO was the most common one in both the early and progressive stages of COVID-19 and was characterized by multiple sized lesions, mainly distributed in the peripheral lung (96.8%). An analysis of thin-section CT images of SARS patients showed that multiple GGOs were the main imaging finding (68.4%) and were distributed in the periphery of the lung (71.8%), with interlobular septal thickening (24.2%) and intralobular interstitial hyperplasia (32.2%), also called the crazy-paving pattern. These findings are very similar to the CT manifestations of COVID-19 [20]. For pneumonia caused by MERS-CoV, GGO was also found on the chest CT images and was mainly distributed in the subpleural and basilar lung regions [21, 22]. Interestingly, pleural effusion was rare and no tree-in-bud pattern or cavitation was found in pneumonia patients infected by the three kinds of coronaviruses. In addition, we found that only one case of COVID-19 (1.6%) presented as consolidation without GGO. Compared with the large amount of consolidation that appears in the early stage of SARS, we speculate that the pathogenicity of SARS-CoV-2 may be less than that of SARS-CoV [23]. Thus, it is necessary to fully understand and discriminate the CT features of COVID-19 at an early stage, which is helpful for the timely isolation and respiratory care of patients and early implementation of infection prevention measures.
In addition to GGO, another important CT characteristic of COVID-19 was multiple GGOs with consolidations, accompanied by interlobular septal thickening, mainly in the peripheral part of the lung. These basic CT features were similar to the findings reported by Huang et al, whose study showed that multiple GGOs with partial consolidation appeared bilaterally on the chest CT images of COVID-19 patients [7]. Similarly, in another chest CT study of a 33-year-old patient diagnosed with COVID-19 in Wuhan, China, multiple GGOs distributed in both the peripheral lungs were found [5]. Therefore, we suggest that multiple GGOs with consolidations mainly in the periphery of the lung are a basic CT feature of COVID-19, which is helpful for the initial screening of COVID-19.
Unexpectedly, the halo sign (20.6%) was the only significantly different CT manifestation in the early stage of COVID-19 among all the CT findings. In our study, the halo sign appeared in only the early stage of COVID-19. We hypothesized that the halo sign rapidly changed into GGO within 1 week due to the aggravation of COVID-19, and no other new halo sign had been formed in the short term. In addition, there were no significant differences in the other CT findings or distribution of lesions between the two stages. For these findings, we speculated that the speed of GGO formation was due to the damage to the alveolar epithelium caused by the virus and may be similar to that of consolidation caused by an inflammatory reaction of the lung tissue, resulting in a change in different types of lesions during the synchronous increase in opacification. In pneumonia caused by SARS-CoV, Ooi et al found that GGO and consolidation formed in the first week of SARS-CoV infection increased in the second week, and only residual strips and reticular shadows were seen in the fourth week [15]. Therefore, the CT manifestations of COVID-19 are different at different stages, which helps the differential diagnosis of COVID-19.
Furthermore, our results showed that the CT scores in the progressive-stage group were significantly greater than those in the early-stage group. Further analysis showed that the CT scores were positively correlated with the maximum diameters of the lesions (r = 0.531), indicating that the range of lesions in the progressive stage was larger than and the degree of inflammation was more serious than that in the early stage. These results also showed that without any antiviral treatment, COVID-19 continued to progress 5–7 days after the onset of symptoms, without any improvement trend. Therefore, necessary clinical measures, including antiviral and supportive therapies, should be administered to prevent disease deterioration. Because of the lack of additional data, the correlation between the CT score and clinical classification and the prognosis of COVID-19 needs further study. Moreover, CT scores showed a significant positive correlation with ages in all 62 patients (r = 0.255). In a previous study on SARS, Grinblat et al considered that age was a risk factor for severe lung injury and poor prognosis of SARS [24]. Therefore, elderly patients need to be treated earlier and more actively than younger patients.
Our study had several limitations. First, because COVID-19 is a novel disease and lacks a series and long-term CT data, we can analyze only the existing information in a retrospective analysis. Moreover, the time of chest CT examination after symptom onset was inconsistent, so it was difficult to summarize the CT appearances that could reflect the whole course of the disease. Second, the sample size in our study was relatively small, and there may be deviation in the comparison of the results of CT findings. Third, most of our cases were imported cases and some were secondary cases. Further research is needed to observe whether virus variation exists in the process of infection and whether virus variation will produce different in CT manifestations. Finally, there was no histopathological evidence from deceased patients.
In conclusion, our study showed that chest CT examination was very effective in detecting pulmonary parenchymal abnormalities in the natural course of COVID-19. Multiple GGOs with consolidations in the peripheral lung was the primary CT characteristic of COVID-19. The halo sign may be a special CT feature in the early stage of COVID-19, while a significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage. In patients with dyspnea and respiratory distress, CT examination is very effective in the preclinical screening of patients with COVID-19.