key: cord-0711173-oht0v33s
authors: Yu, Minhua; Xu, Dan; Lan, Lan; Tu, Mengqi; Liao, Rufang; Cai, Shuhan; Cao, Yiyuan; Xu, Liying; Liao, Meiyan; Zhang, Xiaochun; Xiao, Shu-Yuan; Li, Yirong; Xu, Haibo
title: Thin-section Chest CT Imaging of Coronavirus Disease 2019 Pneumonia: Comparison Between Patients with Mild and Severe Disease
date: 2020-04-23
journal: Radiol Cardiothorac Imaging
DOI: 10.1148/ryct.2020200126
sha: cef05d927c9d3b3a70a3544fe8e157d3762f575b
doc_id: 711173
cord_uid: oht0v33s

PURPOSE: Although CT imaging features of Coronavirus Disease 2019 (COVID-19) pneumonia have already been published in the literature, there was little attention to distinctive imaging features encountered between patients with mild and severe forms of the disease. The purpose was to compare radiological characteristics of COVID-19 pneumonia on thin-section CT upon admission between patients with mild and severe disease. MATERIALS AND METHODS: Seventy COVID-19 pneumonia patients admitted to Zhongnan Hospital of Wuhan University between January 20 and January 27, 2020 were enrolled. Based on the World Health Organization guidelines, 50 patients were categorized with mild form and 20 with severe form based on clinical conditions. Imaging features, clinical, and laboratory data were reviewed and compared. RESULTS: Patients with severe form (median age, 65.00; IQR: 54.75-75.00) were older than those with mild form of disease (median age, 42.5; IQR: 32.75-58.50) (P<0.001). Patients with severe form of disease had more lung segments involved (median number of segments: 7.5 vs. 17.5, P=<0.001) and also larger opacities (median number of segments with opacities measuring 3 cm to less than 50% of the lung segment: 5.5 vs. 2.0, P=0.006; ≥ 50% of lung segment: 7.5 vs. 0.0, P<0.001). They also had more interlobular septal thickening (75% vs. 28%, P<0.001), higher prevalence of air bronchograms (70% vs. 32%, P=0.004), and pleural effusions (40% vs 14%, P=0.017). CONCLUSION: Ground-glass opacities with or without consolidation in a peripheral and basilar predominant distribution were the most common findings in COVID-19 pneumonia. Patients with severe form of the disease had more extensive opacification of the lung parenchyma than did patients with mild disease. Interlobular septal thickening, air bronchograms, and pleural effusions were also more prevalent in severe COVID-19.

CoV-2 first occurred in Wuhan, China, and then quickly spread to other countries in the world (1, 2) . Coronavirus can cause various systemic illnesses in animals but mainly respiratory tract infections in humans, such as severe acute respiratory syndrome (SARS) and

Middle East respiratory syndrome (MERS) (2) . SARS-CoV-2, the cause of COVID-19, is an enveloped RNA virus about 60-140nm in diameter that genetically belongs to lineage B of genus betacoronavirus. Its genetic characteristics are significantly different from SARS-CoV and MERS-CoV. It has been shown to share more than 85% identity with a bat SARS-like CoV (bat-SL-CoVZC45) (2) . According to Guan et Real-time revere transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 is the standard for diagnostic confirmation (4). However, CT imaging could contribute to clinical diagnosis and illness assessment by flagging suspected cases and noninvasively evaluating disease progression (5) . Several studies have reported the epidemiological and clinical information of COVID-19 (1, (6) (7) (8) , including discussion of radiological features (9) (10) (11) (12) ). Yet, comparative analysis of CT findings between patients in different severity groups is scarce. Thus, the purpose of our current study was to compare radiological characteristics of COVID-19 pneumonia on thin-section CT between patients with mild and severe disease. We aimed to identify CT imaging features that could indicate clinical severity among patients with COVID-19 pneumonia.

This retrospective study included a total of seventy patients with COVID-19 pneumonia who were admitted to Zhongnan Hospital of Wuhan University from January 20 to January 27, 2020, who underwent non-contrast-enhanced thin-section chest CT scans upon hospital admission. The inclusion criteria included: (a) positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 on pharyngeal swabs; (b) a thin-section chest CT scan showing any evidence of pneumonia; (c) patients admitted for treatment or isolation. Based on the World Health Organization (WHO) interim guidance for clinical management of patients with COVID-19 (13), the patients were divided into two groups depending on disease severity. Group 1 were patients with mild form, which was defined as (a) maximum respiratory rate < 30 breaths per minute, and (b) oxyhemoglobin saturation (SpO2) > 90% in resting state, and (c) without respiratory failure, acute respiratory distress syndrome (ARDS), or shock. Group 2 were patients with severe form, which was defined as (a) maximum respiratory rate ≥ 30 breaths per min, or (b) SpO2 ≤ 90% in resting state, or (c) respiratory failure needing mechanical ventilation, or (d) ARDS, or (e) shock (13). This retrospective study was approved by the Institutional Review Board of Zhongnan Hospital of Wuhan University and written informed consent was waived.

CT scanning (Discovery 64, GE Medical Systems, Milwaukee, Wis and SOMATOM Definition, Siemens Healthcare, Erlangen, Germany) was performed at the end of full inspiration. The acquisition and reconstruction parameters were as follows: 120kV tube voltage with automatic tube current modulation (100-350 mAs), 1mm slice thickness without interslice gap, using filtered-back-projection (FBP) reconstruction (SOMATOM Definition) I n p r e s s or blended FBP/iterative reconstruction (Discovery 64). Axial images with slice thickness of 1 mm were used for coronal and sagittal reconstructions. Images were displayed on lung windows (window level at -700HU and window width at 1500HU).

We reviewed the CT scans performed within 1 day from admission in all 70 patients. All axial and reconstructed (coronal/sagittal) CT images were independently reviewed by three radiologists with 6 to 7 years of clinical experience using a standard clinical Picture Archiving and Communication System workstation. Any disagreement was resolved by discussion and consensus. All radiologists were blinded to clinical status of the patients. CT findings were reviewed according to the following aspects: location, distribution, size, and type (14) . Location referred to different lobes and segments involved. Distribution was described as peripheral (outer 1/3 of the lung), central (inner 2/3), or both central and peripheral. Opacities were classified into small (diameter <1cm), moderately-sized (diameter 1cm to < 3cm), large (diameter 3cm to < 50% of the segment), or segmental (volume involving 50% of the segment or more), and the number of segments containing a specific category of opacities per patient were counted and compared between groups.

Ground glass opacity (GGO) was defined as hazy increased opacity of lung, with preservation of bronchial and vascular margins (15) . Consolidation was defined as a homogeneous increase in pulmonary parenchymal attenuation that obscures the margins of vessels and airway walls (15) . Crazy-paving pattern was defined as ground-glass opacification with associated interlobular septal thickening (15) . Air bronchogram was defined as pattern of air-filled (low-attenuation) bronchi on a background of opaque (high-I n p r e s s attenuation) airless lung (15) . Parenchymal band was defined as linear opacity that usually extends to the visceral pleura (15) . Pleuroparenchymal interface irregularities were defined as finely irregular and thickened pleural surfaces (16) . Mass-like opacity was defined as a rounded, solid or partly solid opacity of pulmonary lesion greater than 3 cm in diameter (15) .

In addition, interlobular or intralobular septal thickening, bronchiectasis, mosaic attenuation, coarse reticular pattern, lymph nodes (more than 1cm in short-axis diameter), and pleural effusion were recorded as well.

Continuous variables were expressed as median (IQR) and compared with the Mann-Whitney U test; categorical variables were expressed as number (%) and compared by χ² test or

Fisher's exact test between groups. A P-value <0.05 (two-sided) was considered statistically significant. All data were analyzed using SPSS (version 23.0, SPSS Inc., Chicago, IL, USA).

Seventy patients with confirmed COVID-19 pneumonia were included in this study. None of the enrolled patients was immunocompromised. Demographical and clinical characteristics of both groups are shown in Table 1 

There were differences in the number and location of involved segments between Groups 1 and 2. The per patient number of segments involved in Group 2 patients (median, 17.50; IQR:

15.25-18.00) was higher than that among Group 1 patients (median, 7.50; IQR: 3.00-13.50) (P<0.001, see Table 2 ). Affected segments were located predominantly in the lower lobes Table 2) .

The distribution of the lung opacities varied significantly between patients in Groups 1 and 2 (P=0.043) ( 

As shown in Table 4 , there was a significant difference in lung opacity size across groups.

Group 2 patients had a relatively larger number of opacities measuring more than 3 cm (P=0.006) or involving more the 50% of the segment volume (P<0.001) compared to Group 1 patients.

As for the different types of lung opacities, there was no difference between the two groups 

We studied the findings on chest CT at hospital presentation in patients diagnosed with COVID-19 pneumonia, focusing our comparisons between the patients with mild and severe disease. Patients with severe form of disease were older than those with mild form of disease, suggesting that SARS-CoV-2 pathogenicity may depend on the underlying immune response, similar to MERS-CoV (17) . Fever was the most common clinical symptom, while dyspnea occurred more often in patients with severe disease, consistent with previous findings, and in part attributable to the clinical definition of severe disease (7) . We also confirmed that reduced lymphocyte count is a feature that may help diagnosing COVID-19, especially in patients with severe form of disease. All patients with severe symptoms were admitted to the intensive care unit, and the length of hospital stay was longer than that of patients with mild disease. Patients with severe form of the disease underwent chest CT scan later in the course of disease than did those with mild form of the disease. We suspect that the initial symptoms in some patients with the severe form could have been subtle and nonspecific, resulting in later hospital presentation.

As for characteristics in CT images, COVID-19 pneumonia seems to be more extensive in the severe form of disease, involving a larger number of lung segments.

Regarding specific segment involvement, severe form patients were more likely to have I n p r e s s opacities involving nine or more segments. Most of the opacities were located in the lower lobes, which is also seen in other viral pneumonias, such as that caused by Influenza (18) .

Individual opacities also tended involve a larger extension of the lung parenchyma in the severe form of disease.

Most patients had bilateral lung involvement, with both central and peripheral distribution. Unilateral or pure central lung involvement was rare, which is consistent with previous studies (12, 19) . Wong et al. (14) also showed that opacities in SARS were mainly distributed bilaterally and peripherally, while opacities in MERS have been described as predominantly basilar, peribronchovascular, or subpleural (20) .

None of the imaging features described below existed alone in COVID-19 pneumonia but appeared together with multiple other characteristics. The common imaging signs included pure GGO, GGO with consolidation, interstitial thickening, crazy paving, air bronchogram, pleuroparenchymal irregularities, and parenchymal band, which was consistent with previous studies (10, 12) . Such findings may overlap other viral pneumonias; for instance, H1N1 influenza pneumonia also presents GGO in a patchy pattern, with interlobular septal thickening and consolidation (21) . But for H7N9 influenza pneumonia, consolidation is reported to be the most common sign (22) . Pure consolidation, bronchiectasis, mosaic attenuation or mass-like opacity were rare for COVID-19 pneumonia. Patients with mild form of disease showed pure GGO more often than patients with severe disease, while the latter was more frequently associated with pure consolidations. Thus, we can speculate that pure GGO may be associated with early or mild stage of disease, while pure consolidation could indicate severe clinical form or occur at a more advanced stage, consistent with previous reports (9) . The rate of patients with interlobular septal thickening and air bronchogram was higher in patients with severe disease than in patients with mild disease, indicating that interlobular septal thickening and air bronchogram could relate to advanced or I n p r e s s late stage of COVID-19 pneumonia or coexistence of superimposed processes, such as pulmonary edema. Neither interlobular septal thickening nor air bronchogram was specific for COVID-19 pneumonia. Pleural effusion was uncommon, manifesting mainly in patients with severe disease, which may indicate parapneumonic effusion or fluid overload.

Lymphadenopathy is usually rare in viral pneumonias, occurring predominantly in patients with severe form of disease in our study.

There were several limitations in this study. First, these observations were restricted only to the patients presenting to the hospital and admitted for treatment and isolation. Therefore, the conclusions from our study only apply to a small segment of patients affected by the disease. Second, while we included patients with laboratorial confirmation of COVID-19 (23), a controlled investigation for co-infection and comorbidities was not made in this retrospective study. One could speculate that some of the differences encountered between patients with severe and mild forms of disease could be partially attributed to underlying cardiovascular or renal conditions. For example, interlobular septal thickening, pleural Opacities located predominately in the peripheral areas of both lungs. 

What to do next to control the 2019-ncov epidemic?

A novel coronavirus from patients with pneumonia in china

WHO: Global Surveillance for human infection with coronavirus disease (COVID-19

Severe COVID-19 Pneumonia: Assessing Inflammation Burden with Volume-rendered Chest CT. Radiol Cardiothorac Imaging

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: A descriptive study

Clinical features of patients infected with 2019 novel coronavirus in wuhan, china

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china

Emerging coronavirus 2019-ncov pneumonia

Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China

Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia

CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV)

Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance

Thin-section ct of severe acute respiratory syndrome: Evaluation of 73 patients exposed to or with the disease

Fleischner Society: glossary of terms for thoracic imaging

Computed tomography of the pulmonary parenchyma. Part 2: Interstitial disease

Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis

Radiographic and CT Features of Viral Pneumonia

CT Imaging of the 2019 Novel Coronavirus (2019-nCoV) Pneumonia

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings

Initial HRCT findings of novel influenza A (H1N1) infection. Influenza Other Respir Viruses

Emerging H7N9 influenza A (novel reassortant avianorigin) pneumonia: radiologic findings

Evolving status of the 2019 novel coronavirus infection: proposal of conventional serologic assays for disease diagnosis and infection monitoring

The authors have declared that no competing interest exists. ** NA = not applicable: left lung is considered to contain an apicoposterior segment and an anteromedial basal segment rather than the separate segments as seen on the right.