Advance Publication by J-STAGE

Japanese Journal of Infectious Diseases

Coronavirus disease 2019: initial high resolution computed tomography imaging feature analysis: report of seven cases

Jie Huang and Jianping Ding

Received: March 6, 2020. Accepted: April 16, 2020. Published online: May 29, 2020. DOI:10.7883/yoken.JJID.2020.098

Advance Publication articles have been accepted by JJID but have not been copyedited or formatted for publication. Coronavirus disease 2019: initial high resolution computed tomography imaging feature analysis: report of seven cases

Jie Huang1, Jianping Ding1

1Affiliated Hospital of Normal University, 126 Road,

Gongshu , Province, .

Corresponding author ：Jianping Ding，Department of Radiology, Affiliated

Hospital of Hangzhou Normal University, 126 Wenzhou Road, Gongshu

District, Zhejiang Province, China. E-mail: [email protected]

TEL: 15805819016.

Keywords: COVID-19, HRCT, imaging features.

Running title: Imaging features of COVIDManuscript-19

Accepted

1

Summary

The number of reported cases of the new coronavirus disease named “severe acute respiratory syndrome-coronavirus 2” (SARS-CoV-2) has increased since

December 2019. The initial high-resolution computed tomography (HRCT) images of seven patients with diagnosed COVID-19 in the Affiliated Hospital of

Hangzhou Normal University, China, were collected and analyzed. The study showed that all patients had close contact with COVID-19 patient and presented with fever. The initial white blood cell counts of all patients were normal. The percentage of lymphocytes decreased in three patients. In all seven patients with

COVID-19, ground glass opacity (GGO) was found in the HRCT images, mainly distributed in the subpleural region of the lungs. The HRCT scans of six patients showed bilateral lobar lesions, mainlyManuscript peripheral subpleural distribution; one patients showed unilateral lobar involvement. The right lung was more extensively involved than the left lung in six patients, and the lower lobe was more extensively involved than the upper lobe in five patients. The initial chest

HRCT images of the lungs of COVID-19 patients had specific characteristics; the typical manifestations of the bilateral lungs showed extensive GGO-type infiltrate, with thickenedAccepted vascular bundles and focal center consolidation. Pleural effusion, bilateral hilar, and mediastinal lymphadenopathy were rare.

A new strain of coronavirus is the main etiology of severe lung infections characterized by local explosive spreading first throughout China and then

2 throughout the world within a short period of time. The World Health

Organization (WHO) has named the new coronavirus “severe acute respiratory syndrome-coronavirus 2” (SARS-CoV-2) and the pneumonia caused by the virus as COVID-19. Because of the lack of immunity to SARS-CoV-2, the general population is susceptible to infection, with the elderly population being more susceptible to the disease than the younger population and with a higher mortality rate (1). Seven cases have been confirmed in the Affiliated Hospital of

Hangzhou Normal University, China. The detection of viral nucleic acid in a throat swab, the sputum, the lower respiratory tract secretions, or in blood, which has high specificity but poor sensitivity, result in many false negatives in patients who have the disease. Thus, this disadvantage increases the chance of the disease spreading. An initial high-resolution computed tomography (HRCT) scan of the chest is more sensitive than theseManuscript other tests for detecting the disease; therefore, we discuss the imaging features and differential diagnoses of

COVID-19 based on the latest literature, the confirmed cases in our hospital, and the experience in diagnosis and treatment.

Seven confirmed patients, three of whom were men, aged 49–64 years (medianAccepted age, 56 years) were confirmed as having COVID-19 from January to February 2020. The HRCT scans on all 7 patient were performed using

American GE high-speed 16 slice spiral CT. All patients disinfected their hands before entering the CT scanner room and wore N95 protective masks during

3 scans. We selected only the first chest HRCT images for analyses. CT room was isolated and disinfected after scanning. The results of respiratory syncytial virus, adenovirus, and mycoplasma were negative detecting by immune colloidal gold technique, and the kit was purchased from Genesis corporation, with the production batch number of GD20010. The patients were confirmed to be positive for SARS-CoV-2 using RT-PCR.

Ground-glass opacity (GGO), which is a dense shadow similar to opaque glass, was identified in all seven cases, mainly showing subpleural distribution.

Three cases showed pure GGO (Fig. 1A). Multiple ground-glass and solid lesions were found in three patients within all lung lobes and segments (Fig. 1B). Patchy

GGO with bilateral pleural effusion was observed in the right upper lung lobe of one patient, along with vascular bundle thickeningManuscript (Fig. 1C). One patient showed patchy GGO with multiple fibrous bands in both lungs (Fig. 1D).

It has been reported that most patients initially present with fever and fatigue (2), often accompanied by muscle aches or weakness; dyspnea is also an important clinical manifestation. If dyspnea is observed during COVID-19, it indicates that the disease is progressing (2, 3). Some scholars have reported that 48.2%Accepted of patients have cough symptoms that are often manifested as an irritant and dry (2). In addition, a small number of patients may have symptoms other than those of the respiratory tract, such as diarrhea. In our case, all patients had fever and five had an irritant dry cough with or without sputum. These

4 symptoms were the most common clinical features of COVID-19 in our hospital. A small number of patients showed initial symptoms of dyspnea, but we could not rule out that it was actually caused by their anxiety or other factors. Patients with COVID-19 often show lymphocytopenia, with or without leukocyte abnormalities. The initial white blood cell counts in all seven patients were normal. The percentage of lymphocytes decreased in three patients.

Because of the lack of specific clinical manifestations and laboratory tests, the initial chest HRCT scan was particularly important. The HRCT results of

COVID-19 manifestations are diverse (4), as observed in our study. The lesions were mainly located adjacent to or under the pleura of the lung within the lower lung lobes. The density of the lesions was mainly patchy GGO, but also could be accompanied by solid nodular density (5). In our group, the lesions had an obvious tendency of subpleural distributionManuscript in five patients and varied from solid nodules and solid nodules with a peripheral halo sign, patchy or flaky

GGO and cord-like lesions. Some solid nodules were observed within the central area of GGO, which may have been caused by the increase in inflammatory exudation and consolidation within the central alveoli of the lesion. At the same time, we observed that the thickened vascular bundle within

GGOAccepted may be related to the inflammatory response. According to the latest pathological conclusion, GGO may be caused by bilateral diffuse alveolar damage with cellular fibromyxoid exudates (6). There was no obvious phlegm thrombus in the small bronchus, which was consistent with the symptoms. One 5 patient had bilateral pleural effusion, which was considered to be caused by inflammation involving the pleura. No sign of mediastinal lymphadenopathy was observed.

COVID-19 should be differentiated from SARS coronavirus pneumonia, influenza virus pneumonia, mycoplasma pneumonia, bacterial pneumonia, and septic pulmonary embolism caused by infection. There is an 85% similarity in gene homology between the SARS-CoV-2 and the original SARS coronavirus

(7), and its imaging features are very similar. Studies have shown that the lesions from influenza virus pneumonia more likely involve the lower lung (8), which was somewhat similar to those of COVID-19 (4); therefore, it was difficult to distinguish COVID-19 from other viral pneumonia images. The chest CT features of Mycoplasma pneumoniaeManuscript are nodular or patchy consolidation of the air space with cavity formation, show enlargement of the mediastinal lymph node, and show pleural effusion, which is different from

COVID-19 characteristics. The chest CT of bacterial pneumonia show mainly patchy infiltrate and Consolidation, which can be distinguished from COVID-19 characteristics. In addition, COVID-19 must be differentiated from septic pulmonaryAccepted embolisms caused by extrapulmonary infection. Septic pulmonary embolisms can manifest as multiple nodules with or without a cavity, wedge- shaped consolidation, and GGO in the bilateral peripheral zone, but it has the

6 characteristics of short-term variability and an extrapulmonary infection source

(7), which can be differentiated from COVID-19.

In general, to correctly diagnose COVID-19, there must be comprehensive analyses of epidemiology, clinical symptoms, lung imaging, and laboratory results. COVID-19 should be highly suspected in patients with fever and/or cough and typical GGO on an HRCT image, even if the patient has a normal or reduced white blood cell count and epidemic history.

Funding

This study is supported by COVID-19 emergency research funding project of

Zhejiang University (2020XGZX036)

Acknowledgments

This project was supported by the MedjadenManuscript Academy & Research Foundation for Young Scientists (Grant No. MJA20200327).

Conflict of Interest

None to declare

Accepted

7

References

1. Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel

coronavirus (2019-nCoV) in Wuhan, China. J Med Virol. 2020; 92:441-447.

2. Zhou L, Liu HG. Early detection and disease assessment of patients with novel

coronavirus pneumonia. Chin J Tubere Respir Dis. 2020; 43:167-170.

3. Zhang MQ, Wang XH, Chen YL, et al. Clinical features of 2019 novel

coronavirus pneumonia in the early stage from a fever clinic in Beijing. Chin

J Tubere Respir Dis. 2020; 43:215-218.

4. Pan Y, Guan H, Zhou S, et al. Initial CT findings and temporal changes in

patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63

patients in Wuhan, China. European Radiology. Available at < https://

doi.org/10.1007/s00330-020-06731-xManuscript >. Accessed February 18, 2020.

5. Song F, Shi N, Shan F, et al. Emerging Coronavirus 2019-nCoV Pneumonia.

Radiology. 2020; 295:210-217.

6. Zhe Xu, Lei Shi, Yijin Wang. Pathological findings of COVID-19 associated

with acute respiratory distress syndrome. Case Report. Lancet Respir Med. 2020;Accepted 8:420-422. 7. Benvenuto D, Giovanetti M, Salemi M, et al. The global spread of 2019-nCoV:

a molecular evolutionary analysis. Pathog Glob Health. 2020; 114: 64-67.

8

8. Koo HJ, Lim S, Choe J, et al. Radiographic and CT Features of Viral

Pneumonia. Radio graphics. 2018; 38:719-739.

9. Chou DW, Wu SL, Chung KM, et al. Septic pulmonary embolism caused by

a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging

findings, and clinical courses. Clinics (Sao Paulo). 2015; 70: 400-07.

Figure 1A High-resolution computed tomography (HRCT) shows focal peripherally located ground glass opacity (GGO) in the right upper lobe on the lung window with an enlarged vascular bundle.

Figure 1B Multiple spots of ground-glass opacity (GGO) are observed in the bilateral lungs and solid lesions are distributed in the subpleural area. Some neutral areas of GGO show substantial changes.

Figure 1C Scan shows ground-glass opacityManuscript (GGO) in the right upper lobe of the lung with bilateral pleural effusion.

Figure 1D Scans show patchy ground-glass opacity (GGO) located in the lower lobe of the right lung with multiple fibrous bands in both lungs. Accepted

9

Manuscript

Accepted Manuscript

Accepted Manuscript

Accepted Manuscript

Accepted