Since late December of 2019, an explosion in the number of cases of a new acute viral respiratory disease (coronavirus disease [COVID-19]) caused by a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) has been reported in the city of Wuhan in central China. According to the initial investigation, most cases were thought to originate from the Huanan Seafood Wholesale Market in Wuhan [1
]. At the time of the writing of this article, the virus is rapidly spreading to many other cities in China and even to other countries around the world. Although SARS-CoV-2 is a member of the coronavirus family of viruses, it is more distant from SARS coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus, is considered to be a new type of betacoronavirus that infects humans [2
], and on the basis of the current epidemic, is more infectious than SARS-CoV. As of 8:00 p.m. on February 17, 2020, a total of 68,595 confirmed cases of COVID-19 and 1667 deaths were reported. In the present study, we identified 62 patients in Wuhan, China, who had laboratory-confirmed COVID-19 pneumonia and described the CT features of this pneumonia.
Materials and Methods
The ethics committee at Huazhong University of Science and Technology waived the need for informed consent for this retrospective study.
We retrospectively reviewed 118 patients seen with suspected COVID-19 pneumonia from January 16 to January 30, 2020. All patients had abnormal CT findings that suggested pneumonia as the diagnosis. A patient with suspected COVID-19 pneumonia was defined as a patient with pneumonia who met at least three of the following five criteria: fever, a low or normal WBC count or low lymphocyte count, exclusion of other respiratory virus species on the basis of laboratory findings, no relief in symptoms noted after receipt of empirical antimicrobial or antiinfluenza treatment for 3 days, and in particular, an epidemiologic link to the Huanan Seafood Wholesale Market or a history of contact with other patients with COVID-19 pneumonia. A total of 62 patients were confirmed to have COVID-19 nucleic acid on the basis of positive findings for respiratory samples tested using real-time reverse-transcription–polymerase chain reaction. Two of the researchers recorded clinical data, including symptoms, date of onset of symptoms, laboratory examination results, and information regarding other accompanying conditions or diseases.
CT Scanning Protocol
MDCT was performed using either of the following CT scanners: the 16-MDCT LightSpeed scanner (GE Healthcare) or the uCT 760 scanner (United Imaging). The parameters used for the scanning protocol were as follows: patient in the supine position; end inspiratory acquisition; tube voltage, 100–120 kV; tube current–exposure time product, 200–300 mAs; pitch, 1.375 and 0.9125; and section thickness after reconstruction, 1.25 mm. Un-enhanced CT scans were obtained for all patients.
Image Viewing and Evaluation
Two experienced radiologists with 13 and 9 years of experience in thoracic radiology retrospectively reviewed the CT images on a PACS workstation (Synapses, Fujifilm) with multiplanar reconstruction tools and reached a decision in consensus. The images were viewed in lung window settings (width, 1000–1500 HU; level, 700 to −550 HU) and mediastinal window settings (width, 300–350 HU; level, 30–40 HU). The predominant patterns seen on CT images were classified into three major categories: lung, bronchial, and pleural changes. Each major category was divided into subcategories. Lung changes were classified into the following eight subcategories: ground-glass opacities (GGO; increased attenuation without obscuration of the underlying lung vessels) [3
], consolidation (homogeneous increased intensity of lung parenchyma with obscuration of the underlying vessels), GGO plus a reticular pattern (a reticular shadow on the background of GGO and thickening of the interlobular septum and interlobular septum, showing paving stone sign) [4
], vacuolar sign (a vacuole-like transparent shadow of < 5 mm in length observed in the lesion), microvascular dilation sign (dilated small vessels in the lesion), fibrotic streaks (an irregular strip shadow), a subpleural line (an arc-shaped linear shadow 2–5 cm in length appearing parallel to the chest wall), or a subpleural transparent line (a thin and transparent line lying between the lesions and the visceral layer of pleura). Bronchial changes were classified into two subcategories: air bronchogram (an air-filled image of bronchus in lung lesions) and bronchus distortion. Pleural changes were classified into three subcategories: thickening of the pleura, pleural retraction sign (lesions present close to the visceral pleura and pull pleura), or pleural effusion. Distribution of the lung lesions was classified as predominantly peripheral (involving mainly the peripheral region comprising one-third of the lung), central (involving mainly the central region comprising two-thirds of the lung), or peripheral plus central (involving both the peripheral and central regions) [5
]. Because no cases of lymphadenopathy and pneumothorax were found, those two signs will not be described in the present study.
The extent of involvement on thin-section CT images was also assessed by the two radiologists. Each side of the lung was divided (from top to bottom) into three zones: the upper zone (above the carina), the middle zone (from the carina to the inferior pulmonary vein), and the lower zone (below the inferior pulmonary vein). Each zone was then divided into two areas: the anterior area (the area before the vertical line of the midpoint of the diaphragm in the sagittal position) and the posterior area (the area after the vertical line of the midpoint of the diaphragm in the sagittal position). Finally, bilateral lungs were divided into 12 zones altogether. The degree of involvement in each lung zone was scored as follows [6
]: a score of 0 denoted no involvement; 1, < 25% involvement; 2, 25% to less than 50% involvement; 3, 50% to less than 75% involvement; and 4, ≥ 75% involvement. Scores were recorded and summed for each lung zone, with a maximum possible score of 48.
Data were recorded using spreadsheet software (Excel 2010, Microsoft) and were analyzed using statistical software (SPSS, version 22.0, IBM). Continuous variables were expressed as mean (± SD) values. The Kolmogorov-Smirnov test was used for the normal distribution test, and continuous variables were compared using the Mann-Whitney U test. The frequency of CT signs was expressed as the number (percentage) of occurrences and was compared for cases of early- versus advanced-phase disease using the chi-square test or the Fisher exact test. Differences for which p < 0.05 were considered statistically significant.
COVID-19 pneumonia is a new, highly contagious viral pneumonia caused by a novel coronavirus (SARS-CoV-2) of unclear origin. In this study, we investigated 62 patients with confirmed COVID-19 pneumonia. Most (62.9%) of the infected patients were men. In terms of symptoms, fever occurred in 87.1% of patients; coughing and sputum, in 45.2%; muscle pain, 32.3%; shortness of breath, 24.2%; fatigue, 22.6%; and gastrointestinal symptoms such as abdominal pain and diarrhea, 14.5%. In addition to respiratory and systemic symptoms of viral infection, some patients with COVID-19 pneumonia presented with a gastrointestinal symptom as the initial symptom; this finding suggests that gastrointestinal symptoms may be associated with the pathogenesis of COVID-19 pneumonia as a result of the virus binding to human receptor angiotensin-converting enzyme 2 [9
], which also shows high expression in the gastrointestinal tract [10
]. In terms of laboratory findings, 80.0% of patients had a decreased lymphocyte count [11
], and 50.0% of patients had a decreased percentage of lymphocytes. Of 27 patients who underwent evaluation of the erythrocyte sedimentation rate and hs-CRP level, 66.7% had an increased erythrocyte sedimentation rate, and 100.0% had an elevated hs-CRP level. Therefore, a decreased lymphocyte count and an elevated hs-CRP level were the most sensitive parameters.
In reviewing and analyzing the CT features of 62 cases of COVID-19 pneumonia, we found that cases were most often seen to manifest as multiple lesions on the initial CT scan (83.9%); however, 16.1% of cases manifested as single lesion, and of these cases, 70.0% occurred in the inferior lobe of the right lung. When patients with single and multiple lesions were compared, multiple lesions were identified on imaging performed at a mean of 6.6 ± 4.0 days after onset of symptoms, whereas single lesions were identified on imaging performed at a significantly earlier phase of the disease (2.2 ± 1.8 days). This may be because of the innate anatomic features of the right inferior lobar bronchus. The bronchus of the right lower lobe of the lung is straighter and steeper than other bronchial branches, and the angle between the right lower lobe and the long axis of the trachea is smaller, so in the early phase of the disease, the virus is more likely to invade the branches of the right inferior lobar bronchus and cause infection. Considering the range of involvement, we found that lesions showed a predominantly peripheral distribution (75.8%). The middle and lower zones and the posterior area of both lungs were significantly more involved.
We found diversified CT patterns of COVID-19 pneumonia, including lung changes (GGO [40.3%], consolidation [33.9%], GGO plus a reticular pattern [62.9%], vacuolar sign [54.8%], microvascular dilation sign [45.2%], fibrotic streaks [56.5%], subpleural line [33.9%], subpleural transparent line [53.2%]), bronchial changes (air bronchogram [72.6%] and bronchus distortion [17.7%]), and pleural changes (thickening of pleura [48.4%], pleural retraction sign [56.5%], and pleural effusion [9.7%]). On CT, the COVID-19 pneumonia was seen to have a rather mixed pattern involving both lung parenchyma and lung interstitium [12
]. The virus first invaded the pulmonary interstitium, which was characterized by edema and thickening of the interlobular septum, interlobular interstitium, subpleural interstitium, interlobular central interstitium, and peribronchovascular inter-stitium, manifesting as GGO. Consolidation might represent further infiltration of the parenchyma. The vacuole sign could be caused by an incompletely filled alveolar cluster in the exudative lung parenchyma. The micro-vascular dilation sign probably indicated increased blood supply to the inflammatory area. Air bronchogram was formed by bronchus containing air in consolidation. GGO plus a reticular pattern represented thickening of the interlobular septum resulting from the GGO, which ultimately evolved into the subpleural line. Fibrotic streaks indicated local inflammatory absorption and residual fibrosis, and bronchus distortion suggested that the local inflammation absorbed and retracted the bronchus inside or surrounded it. The pleura were often involved and were characterized by thickening and retraction resulting from the inflammatory reaction.
In early-phase COVID-19 pneumonia (≤ 7 days after the onset of symptoms), bronchus distortion (10.0%) and pleural effusion (2.5%) were relatively rare compared with other signs (frequency, 27.5–62.5%). In advanced-phase disease (8–14 days after the onset of symptoms), GGO plus a reticular pattern (86.4%), vacuolar sign (81.8%), air bronchogram (81.8%), fibrotic streaks (90.9%), and the subpleural transparent line (72.7%) were relatively more common than other signs (frequency, 22.7–59.1%). Compared with early-phase disease, advanced-phase disease was associated with a significantly increased frequency of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, air bronchogram, bronchus distortion, a subpleural line, a subpleural transparent line, and pleural effusion, but GGO was significantly decreased. These changes suggested that GGO was a relatively early sign in the course of the disease and that in the advanced phase, the involvement of lung parenchyma and interstitium was aggravated but was accompanied by repair changes. There was no significant difference between early-phase disease versus advanced-phase disease in terms of consolidation, the microvascular dilation sign, thickening of pleura, and the pleural retraction sign.
The present study has two limitations. First, because the course of COVID-19 pneumonia is short, changes seen on CT over its entire course have not been completely tracked and described for all patients. Second, there is not enough pathologic data on these patients for a comparative study to be performed.
In conclusion, CT findings for patients with COVID-19 pneumonia showed that the disease has a mixed and diverse pattern, with both lung parenchyma and interstitium involved. The presence of GGO and a single lesion at the onset of COVID-19 pneumonia suggested that the disease was in its early phase. CT signs of aggravation and repair coexisted in examinations of patients with advanced-phase disease. Pleural effusion might occur in the advanced phase. Multifocality as well as primary distribution of lesions in the middle and lower zones and the posterior area of the lungs were rather characteristic manifestations. A decreased lymphocyte count and an elevated hs-CRP level were the most common laboratory findings.