Dynamic changes in clinical and CT characteristics of COVID-19 cases with different exposure histories: a retrospective study

The ethics committees of Beijing YouAn Hospital, Capital Medical University, approved this retrospective study, which involved no risk for the subjects. Written informed consent was waived. All COVID-19 patients were enrolled from Beijing YouAn Hospital, Capital Medical University, which is one of the designated hospitals for treating COVID-19 patients in Beijing. Inclusion criteria included: (a) confirmation by RT-PCR assay for SARS-CoV-2, which was performed before admission at the Center for Disease Control (CDC), Beijing, China; (b) at least one CT follow-up during hospitalization; (c) at least one CT follow-up after discharge as of March 10, 2020. Exclusion criteria included: (a) influenza A (HIN1, H7N9) and other common bacterial or viral pneumonia; (b) age < 14 years old. A total of 53 patients were included from January 21, 2020 to March 10, 2020. The study flow diagram is presented in Fig. 1. Patients were further divided into 2 groups based on different epidemiological history (Wuhan group: recently lived in or traveled to Wuhan, totaling 30 cases; non-Wuhan group: close contacts or unknown exposure, totaling 23 cases).

Epidemiological, clinical, and laboratory data were obtained from electronic medical records. Detailed clinical information included demographics, current medical history, epidemiological history, past history, symptoms and signs, treatment measures, days of admission. The disease onset date was defined as the day when the symptoms were first noticed. Treatment measures for non-severe patients included symptomatic supportive care (ibuprofen, lianhua qingwen capsule, liver protection treatment, correct hypoalbuminemia), antiviral therapy (lopinavir/ritonavir). The lianhua qingwen capsule is a Traditional Chinese Medicine (TCM) formula, which has antiviral and anti-inflammatory effects and is used to treat respiratory tract infectious diseases in China [20]. Treatment measures for severe patients included symptomatic supportive care, antiviral therapy, oxygen support, respiratory support, antibiotic therapy, and corticosteroid therapy. Laboratory tests included white blood cell (WBC), lymphocytes (LYM), percentage of LYM (%LYM), neutrophil (NEUT), percentage of NEUT (%NEUT), C-reactive proteins (CRP), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), globulin (GLOB), albumin/globulin ratio (A/G), glomerular filtration rate (eGFR), creatine kinase (CK), influenza antibody tests, and RT-PCR assay for SARS-CoV-2.

The initial CT examinations of all patients were obtained on the day of admission. The median duration from disease onset to CT scan of Wuhan and non-Wuhan cases was 4.5 days (IQR, 3.8–6.3) and 5 days (IQR, 4.0–7.0) respectively. All chest CT scans were performed with a 256-section scanner (Brilliance iCT, Philips Healthcare, Cleveland, OH, USA) without the use of intravenous contrast. The CT examination parameters were as follows: 120 kV; automatic tube current (100 mA–400 mA); iterative reconstruction technique; detector collimation, 128 × 0.625 mm; section thickness, 5 mm; rotation time, 0.4 s; pitch, 0.914; matrix, 512 × 512; and holding breath during end-inspiration. Before January 27, 2020, the chest CT scans were obtained with a slice thickness of 5 mm. To obtain thin-section high resolution images, the chest CT images after January 27, 2020 were reconstructed with a 1.0 mm slice thickness and a 1.0 mm interval. The thin-section multiplanar reconstruction post-processing images in sagittal and coronal positions were then obtained. Two windows were used: lung window (window width, 1500 HU; window level, − 500 HU) and mediastinal window (window width, 350 HU; window level, 50 HU). All follow-up images were obtained through application of the the same protocol as that of the initial scans. The median duration from initial CT to the first follow-up CT scan was 4 days (IQR, 4.0–5.0), and all patients, including the 30 cases in the Wuhan group and the 23 cases in the non-Wuhan group underwent the first follow-up. The median duration from initial CT to the second follow-up CT scan was 8 days (IQR, 7.7–10.0), and 46 patients (26 Wuhan, 20 non-Wuhan) underwent a second follow-up. Seven patients with mild CT abnormalities were discharged without the second follow-up because the results of the first follow-up showed that the lesions were absorbed obviously. As of 10 March 2020, 45 patients (25 Wuhan cases and 20 non-Wuhan cases) had been followed up for approximately 2 weeks after discharge, and 18 patients (12 Wuhan and 6 non-Wuhan) had been followed up for approximately 4 weeks. Ten of these patients (7 Wuhan and 3 non-Wuhan) were followed up at both 2 and 4 weeks after discharge.

In the condition of blindness to patients’ clinical information, all CT images were reviewed independently by three radiologists (R.L., C.J., and H.L.) who have between approximately 9 to 32 years of experience in thoracic CT imaging. A final decision was based on consensus when there was a discrepancy in opinion.

The CT images were evaluated for the following features: (1) the presence of pure ground-glass opacification (GGO) (defined as slightly increased lung attenuation with no obscuration of the underlying vascular architecture), patch shadowing (a state between GGO and consolidation, described as GGO density increased with interlobular septal thickening or intralobular networks in GGO, or GGO with consolidation) or consolidation (defined as markedly increased lung attenuation obscuring the underlying vessels); (2) the subpleural or non-subpleural location; (3) the extent of lung involvement, which was assessed independently for each of the five lobes. Each lung lobe was evaluated and assigned a score based on the following: 0 when no involvement, 1 when less than 25% involvement, 2 when 26%—50% involvement; 3 when 51%—75% involvement, and 4 when 76% or more involvement. The total score was the summation of each lobe score (the maximum score being 20), which provided the extent of overall lung involvement. Similar evaluation methods have been reported [9]. The CT scores of lung involvement were also obtained in the follow-ups during hospitalization. The progression or improvement of the disease over time was assessed based on the extent and the density change of lung opacities on CT images.

The Shapiro-Wilk (S-W) test was used to assess the normality of continuous variables. Normally distributed data were presented as means (standard deviation, SD) and were compared between different groups with two independent t-test samples. Non-normally distributed data were presented as median (interquartile ranges, IQR) and were compared with the Mann-Whitney U test. Paired t-test or two related samples Wilcoxon signed ranks test was used to evaluate the differences of variables between the initial and follow-ups examination. Categorical variables were described as frequency rates or percentages and were compared using χ² or Fisher’s exact test between groups, where appropriate. Spearman correlation was performed for continuous and categorical variables. Two-sided p values less than 0.05 were considered statistically significant. All analyses were performed with the use of IBM SPSS Statistics version 20.0 (IBM, Armonk, NY, USA).

The demographic and clinical characteristics are shown in Table 1. The 53 patients included 31 (58.5%) women and 22 (41.5%) men, and the mean age was 50.2 years old (SD, 15.2). The most common complaints were fever (88.7%), cough (64.2%) and fatigue (34%). The common coexisting disorder was hypertension (17%). The median time from onset to admission was 5.0 days (IQR, 4.0–7.0). 76.7% of patients in the Wuhan group were non-severe, while 91.3% of patients in the non-Wuhan group were non-severe. There was no significant difference between the Wuhan and non-Wuhan groups in demographic and clinical characteristics.

Data for CT and laboratory findings at admission are listed in Table 2. Ground-glass opacity (86.8%) and patchy shadowing (50.9%) were the main findings, and the most common location (88.7%) was subpleural (Fig. 2). The median CT score of lung involvement was 4 (IQR, 3.0–6.0). Most patients presented elevated levels of CRP (13.7, IQR 4.1–30.0), decreased LYM (1.13, SD 0.49), ALB (36.7, SD 3.7) and A/G ratio (1.02, SD 0.20). Compared to the non-Wuhan group, while the CRP and CT score of lung involvement in the Wuhan group had a tendency to increase, and the lymphocytes, albumin, and A/G had a tendency to decrease, there was no statistically significant difference.

It was noticeable that the disease improvement or progression ratio of the Wuhan and non-Wuhan groups were different, based on the extent and density change of lung opacities on chest CT images. In total 66.7% of patients (20/30) in the Wuhan group and 47.8% of patients (11/23) in the non-Wuhan group showed progression at the first follow-up of 4 days (Table 3, Fig. 2). The improvement ratio of the non-Wuhan group (100%, 20/20) was higher than that of the Wuhan group (69.2%, 18/26) on the CT follow-up of 8 days (p = 0.006) (Table 3, Fig. 2).

To further evaluate the dynamic changes in CT characteristics during the disease process, we analyzed the imaging findings from 46 patients (26 Wuhan cases and 20 non-Wuhan cases), who had undergone all chest CT examinations, including admission, follow-up of days 4, and second follow-up of days 8. The within-group comparison showed that the CT scores of lung involvement in Wuhan group increased at the first follow-up (p = 0.015) compared to the examination at admission (Fig. 3, Table S1), which suggested disease progression in the short-term follow-up. Comparison of the Wuhan and non-Wuhan groups showed that the CT scores of the non-Wuhan group were significantly lower than that of the Wuhan group at the second follow-up (p = 0.006) (Fig. 3, Table S2).

As with CT features, we also analyzed the laboratory indicators of 42 patients (25 Wuhan cases and 17 non-Wuhan cases), who had undergone all examinations at admission, follow-up at day 4, and a second follow-up at day 8. The level of ALB and A/G of Wuhan group significantly decreased at the first follow-up (p < 0.001, p < 0.001), and similar results were observed in the non-Wuhan group (p = 0.014, p < 0.001) (Fig. 4, Table S3). Compared to the first follow-up, the LYM significantly increased (p = 0.043), the CRP significantly decreased in the Wuhan group (p = 0.005) at the second follow-up. For the non-Wuhan group, LYM and A/G significantly increased (p = 0.019 and 0.035), while the CRP significantly decreased (p = 0.015) (Fig. 4, Table S3). Changes in the above indicators at the second follow-up show an improvement in the clinical condition. There was no significant difference in laboratory indicators between the Wuhan and non-Wuhan groups at initial examination, or at follow-up on day 4 or 8.

At initial examination, the CT scores of lung involvement were negatively correlated with LYM (r = − 0.318, p = 0.020), ALB (r = − 0.556, p < 0.001), A/G (r = − 0.656, p < 0.001), and positively correlated with CRP (r = 0.616, p < 0.001), respectively (Fig. 5). Spearman correlation was performed between the CT score and laboratory finding of all 53 cases.

At the first follow-up of days 4, the CT scores of lung involvement were negatively correlated with LYM (r = − 0.428, p = 0.002), ALB (r = − 0.553, p < 0.001), A/G (r = − 0.583, p < 0.001), and positively correlated with CRP (r = 0.615, p < 0.001), respectively (Fig. 5). A total of 53 cases underwent the first CT follow-up, but 1 case was dropped due to the absence of laboratory tests at the point of the first CT follow-up. Therefore, the Spearman correlation was performed with the indicators of 52 patients.

The CT scores of lung involvement were negatively correlated with ALB (r = − 0.596, p < 0.001), A/G (r = − 0.590, p < 0.001), and positively correlated with CRP (r = 0.347 and 0.025) at the second follow-up (8 days later), respectively (Fig. 5). A total of 46 cases underwent the second CT follow-up, 4 cases were dropped due to the absence of laboratory tests. Therefore, the spearman correlation test was performed between the CT scores and laboratory indices of 42 patients.

In this study, the average length of hospital stay was 13.9 days (SD, 4.1), and the median interval between symptom onset and discharge was 19.0 days (IQR, 16.0–23.0). Compared with the non-Wuhan group, the average length of hospital stay and interval between symptom onset and discharge in the Wuhan group had a tendency to be longer but the difference was not statistically significant.

Forty-five patients (25 Wuhan cases and 20 non-Wuhan cases) were first followed up of 2 weeks after discharge. The CT images show partly absorption with decreased size and density of the lesions in all Wuhan cases (100%, 25/25) and 80% non-Wuhan cases (80%, 16/20) (Fig. 2). Moreover, the complete absorption of lesions in 4 non-Wuhan cases (20%, 4/20) is shown in Table 3. Subsequently, 10 of 45 patients (7 Wuhan cases and 3 non-Wuhan cases) were followed up at 4 weeks after discharge. Complete absorption of lesions was shown on the CT imaging of 4 Wuhan patient and 2 non-Wuhan patients (Fig. 2), and CT images of the other 3 Wuhan patients and 1 non-Wuhan patient still exhibited small-scale lesions. Eight patients (5 Wuhan cases and 3 non-Wuhan cases) were followed up only 4 weeks after discharge, and the complete absorption of lesions was found. As with the CT images, laboratory indicators of all patients such as CRP, lymphocyte, albumin and A/G ratio returned to normal between 2 to 4 weeks after discharge, and the RT-PCR assay results of all patients after discharge were negative.