key: cord-0762750-ptlh8oqx
authors: Wei, Jiangping; Lei, Pinggui; Yang, Hong; Fan, Bing; Qiu, Yingying; Zeng, Bingliang; Yu, Peng; Lv, Jian; Jian, Yinchao; Wan, Chengfeng; Pang, Peipei
title: Analysis of thin-section CT in patients with coronavirus disease (COVID-19) after hospital discharge
date: 2020-05-15
journal: Clin Imaging
DOI: 10.1016/j.clinimag.2020.05.001
sha: 4710827834deafd58ec19392945831f7a1243644
doc_id: 762750
cord_uid: ptlh8oqx

PURPOSE: To analyze clinical and thin-section computed tomographic (CT) data from the patients with coronavirus disease (COVID-19) to predict the development of pulmonary fibrosis after hospital discharge. MATERIALS AND METHODS: Fifty-nine patients (31 males, 28 females; mean age: 41 years, range: 25 to 70 years) with confirmed COVID-19 infection performed follow-up thin-section CT of the thorax. After 31.5 days of hospital admission, the results of thin-section CT were analyzed for parenchymal abnormality (ground-glass opacification, interstitial thickening, and consolidation) and evidence of fibrosis (parenchymal band, traction bronchiectasis, and irregular interfaces). Patients were analyzed based on the evidence of fibrosis and divided into two groups, group A (with CT evidence of fibrosis) and group B (without CT evidence of fibrosis). Patient demographics, length of stay (LOS), rate of intensive care unit (ICU) admission, peak C-reactive protein level, and CT score were compared between the two groups. RESULTS: Among the 59 patients, 89.8% (53/59) patients had a typical transition from early phase to advanced phase and advanced phase to dissipating phase. Out of 59 patients, 39% (23/59) patients developed fibrosis (group A), whereas 61% (36/59) patients did not show definite fibrosis (group B). Patients in group A were older (mean age, 45.4 vs. 33.8 years), with longer LOS (19.1 vs. 15.0 days), higher rate of ICU admission (21.7% (5/23) vs. 5.6% (2/36)), higher peak C-reactive protein level (30.7 vs. 18.1 mg/L), and higher maximal CT score (5.2 vs. 4.0) than those in group B. CONCLUSIONS: Pulmonary fibrosis may develop early in patients with COVID-19 after hospital discharge. Older patients with severe illness during treatment were more prone to develop fibrosis according to thin-section CT results.

Coronavirus disease (COVID-19) refers to pneumonia caused by novel coronavirus infection [1] . In December 2019, some hospitals in Wuhan City, Hubei Province had successively detected multiple cases of unexplained pneumonia with a history of exposure to South China seafood market, currently confirmed as an acute respiratory infectious disease caused by 2019-nCoV infection [2, 3] . On February 11, 2020, the World Health Organization (WHO) announced that the 2019-nCoV infection of pneumonia was named COVID-19. As of March 1st, 2020, a total of 79971 cases were diagnosed and 2873 deaths were reported with COVID-19 and the number is still rising.

Medical imaging is important in the diagnosis and treatment of COVID-19 [4, 5] . Typical imaging manifestations commonly occurring in the peripheral lung include pure ground-glass opacity (pGGO) or mixed ground-glass opacity (mGGO) or consolidation in both lungs [6] [7] [8] .

However, the progress of the disease after the treatment and discharge of the patient was rarely reported, and it is unclear whether there is a residual focus or fibrosis. The purpose of this study is to analyze clinical and radiological data in the predicition of the development of pulmonary fibrosis.

This retrospective study was approved by the research ethics committee and exempted from informed consent.

In this multi-center study, a total of 208 patients with COVID-19, discharged between January 18 th , 2020 to March 1 th , 2020, from four medical institutions in China (** Hospital) were enrolled. Out of 208 patients, 59 receiving CT follow-up within one month after discharge were included for this study. The other patients had been scheduled to undergo thin-section CT, but it

had not yet been performed. Patient selection was consecutive in each of the four institutions.

The average CT follow-up time is 31.5 days (range, 24 to 39 days) after the initial hospital admission and 16.3 days after discharge (range, 7 to 25 days).

Scanning was performed using GE Optima 660 (GE Medical Systems; Milwaukee, WI), Philips Brilliance CT (Philips, Amsterdam, Netherlands) or Siemens Emotion 16 scanner (Siemens Healthiness, Erlangen, Germany). The patients were in supine and head-first position and received scanning with breath held. Parameters: 120 kV; 100-250 mAs; layer thickness 1-2.5mm; pitch, 1-1.5; matrix, 512 × 512. No contrast was administered. All images were transmitted to the post-processing workstation and reconstructed using high-resolution and conventional algorithms.

All CT images were reviewed by two radiologists (**, with 15 and 14 years of experience in chest imaging, respectively), and final decisions were established by consensus. In order to evaluate the scope and extent of involvement of the two lungs, the CT scoring criteria used were as follows: five lobes together in both sides, each lung lobe scaling from 0-4 points, add up to the total score of 0-20 points [11] (Table 1 ). If the patient had multiple CT examinations during hospitalization, the first CT and the most severe CT examination during the disease progression were scored separately. Ground-glass opacity (GGO) showed a slight increase in density, but the bronchial vascular bundles could still be displayed. Consolidation was defined as opacification in which the underlying vasculature was obscured. Fibrosis was defined as parenchymal bands, irregular interfaces (bronchovascular, pleural, or mediastinal), and traction bronchiectasis [12] .

Patients with evident fibrosis were set as group A, and those without evident fibrosis was classified as group B.

Patient sex, age, LOS, admission to the ICU, peak C-reactive protein (CRP) level, and CT score were compared between the two groups. CT score includes the first CT during the hospital stays and the CT on peak opacification.

J o u r n a l P r e -p r o o f SPSS17.0 software (Chicago, IL) was used for statistical analysis. Quantitative data are shown as the mean ± standard divisions (SD), and compared through the analysis of variances or independent sample t-tests. Qualitative data were compared using a chi-square test. P < 0.05 was considered statistically significant.

Among the 59 patients, 89.8% (53/59) patients had a typical transition from early phase to advanced phase, and then from advanced phase to dissipating phase [9, 10] showed incomplete absorption of GGO and thickening of the interlobular septum while three cases showed complete absorption (Fig 1-2 ).

Patients in group A were older than those in group B (mean age, 45.4 vs 33.8 years)(P=0.001). The LOS of patients in group A was longer than that of patients in group B (19.1 vs 15.0 days)(P=0.001). Percentage of patients in ICU in group A was higher than Group B (21.7% vs 5.6%)(P=0.061). The peak C-reactive protein level was higher in patients of group A than that in patients of group B( 30.7 vs 18.1mg/L)(P=0.041). The normal range of C-reactive protein level is between 0-5 mg/L. The first pulmonary CT scan was obtained 2±2 days (range: 0-5) after the onset of symptoms. The first CT score of group A and group B were 2.0, 1.9, respectively (P=0.90). The peak CT was obtained 8±4 days (range: 5-14) after the onset of symptoms. The peak CT score of group A and group B were 5.2, 4.0 , respectively (P=0.06) ( Table 2 ).

announced that the COVID-19 epidemic was a public health emergency of international concern [3, 13, 14] . Chinese medical staff worked hard to combat the epidemic. As of March 1st, 2020, 41684 patients were cured and discharged. This study retrospectively analyzed the data of four medical institutions in different regions of China. Patient follow-up has only just begun. Our study population represented a sample those patients in whom thin-section CT after hospital discharge had already been performed.

The results of this study showed that 89.8% (53/59) of the cases had a typical progression from early phase to advanced phase and advanced phase to dissipating phase [9, 10] . The other six patients had milder lesions, and the imaging manifestations directly entered the dissipating phase from the early phase, and three patients had complete lesion absorption. It is suggested that COVID-19 may be self-limiting. Therefore, timely treatment can shorten the course of the disease, accelerate the absorption of lesions, and the recovery process. Follow-up after discharge showed that 39% of patients had residual fibrosis, 61% had no clear fibrosis.

According to Antonio GE [12] , in severe acute respiratory syndrome (SARS), the early lung fibrosis rate reaches as high as 62%. COVID-19 has a lower rate of fibrosis than SARS. In addition, SARS causes severe lung parenchymal damage, with a high probability of causing "white lung" and mediastinal emphysema [15] , while COVID-19 is relatively mild in symptoms, with no mediastinal emphysema seen in this group of cases. This group of cases shows that elderly patients have a higher chance of developing fibrosis.

The patients in the fibrosis group have a higher CT score, longer LOS, and a higher proportion of ICU admissions, suggesting that patients with multiple lesions or severe conditions are more prone to fibrosis. In addition, the patients in the fibrosis group have a high level of C-reactive protein. The C-reactive protein rises sharply in the plasma when the body is infected or tissues are damaged, it activates the complement system and strengthens the phagocytosis of phagocytes, and removes pathogenic microorganisms that invade the body [16, 17] . It plays an important protective role in the body's natural immune process, which may accelerate fibrosis formation during this process.

Some limitations of the current study have to be acknowledged. Firstly, small sample size and short follow-up time. Therefore, studies in the large samples are needed to confirm it.

Secondly, fibrosis was not been confirmed by histology even though the imaging manifestations were typical. Finally, all patients in the study were discharged from rehabilitation. Their course of the disease was relatively light, and severe cases and deaths were not included in the study.

In summary, the vast majority of cases in this group A and B have a typical progression from the early phase, advanced phase to the dissipating phase. Fibrosis was developed in 39% of patients , which is more likely to occur in the elderly and people with a large range of lesions and severe conditions. This study is only preliminary experience, which requires long-term, large sample follow-up to reveal the evolution of COVID-19 and the significance of fibrosis.

J o u r n a l P r e -p r o o f 

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Novel Coronavirus Pneumonia Outbreak in 2019: Computed Tomographic Findings in Two Cases

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Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study

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