Abstract

Introduction

Since December 2019, many gathered cases of “unknown viral pneumonia” have been reported, initially linked to exposure at the Huanan Seafood Market, Wuhan, China (1). A novel coronavirus was detected, capable of infecting humans, on 6 January 2020 (2, 3) and termed COVID-19 (2). By 7 February 2020, there were 43103 confirmed cases with 2019-nCoV (COVID-19) pneumonia in 25 countries (4). Similar to other coronaviral pneumonia such as severe acute respiratory syndrome caused by coronavirus and Middle East respiratory syndrome coronavirus, COVID-19 can also lead to acute respiratory distress syndrome (ARDS) (1, 5). With the gradual recognition of COVID-19 pneumonia, professional consensus, guidelines, and criteria were steadily established with the aim of preventing transmission and facilitating diagnosis and treatment (6-8).

From the recently published literature, thetypical radiological imaging of COVID-19 pneumonia demonstrated clear destruction of the pulmonary parenchyma including interstitial inflammation and extensive consolidation, similar to the previously reported coronavirus infection (1, 9-11). However, some patients with COVID-19 pneumonia consistently demonstrated no hypoxemia or respiratory distress during the course of hospitalization. The purpose ofthis study was determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery.

Materials and Methods

This study was approved by the Ethics of Committees of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent for this retrospective study was waived. The anonymous data was collected and analyzed to facilitate better clinical decisions and treatment.

Results

1. Patient characteristics:

A total of 21 patients(6 males and 15 females) were included in the study. The average age was 40 ± 9 years (Table 1). The most prevalent presenting symptoms were fever (86%)and cough (57%). Four patients had no chest CT abnormalities at base line evaluation. Laboratory investigations were often normal, with the most frequent abnormalities being a mildly elevated C-reactive protein (17.2±20.0mg/L), erythrocyte sedimentation rate (33±27s), lactate dehydrogenase (242±73 U/L), and D-dimer (0.93±1.43) (Table 1). The first pulmonary CT scan was obtained 2±2 days (range: 0–9) after the onset of symptoms. A total of 82 pulmonary CT scans were performed and each patient underwent an average of 4±1 CT scans (range: 3-6) with a mean interval of 4±1 days (range: 1-8 days) (Figure 1). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days).

Table 1:

Characteristics of the patient cohort.

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Figure 1:

Timeline of the pulmonary CT scans. d=days.

2. Pulmonary CT Evaluation

Ground glass opacities (GGO), crazy-paving pattern (GGO with superimposed inter- and intralobular septal thickening) and consolidation were the most frequent CT findings in mild COVID-19 pneumonia (Figure 2). No mediastinal lymphadenopathy was observed. In most patients (18 out of 21) the total CT score increased to approximately ten days after the onset of symptoms, and then gradually decreased (Figure 3a). The total CT score peaked at ten days after the onset of initial symptoms (Figure 3, calculated total CT Score, 6 at 10 days).

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Figure 2:

Chest CT findings of COVID-19 pneumonia on transaxial images. (a) GGO; (b) crazy-paving pattern (GGO with superimposed inter- and intralobular septal thickening); (c) Consolidation. All images have the same window level of -600 and window width of 1600.

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Figure 3:

Change in lung involvement on chest CT from time of onset of initial symptoms (in days). (a) The dynamic changes in total CT score for each patient; (b) Peak total CT lung involvement occurred at day 10 (curve fitting equation: y=0.001*x³-0.083*x²+1.329x+0.373, in which x = time from the onset of the initial symptoms, y = total CT score of the pulmonary involvement; R²=0.25, p<0.001). Quartiles of patients between 0 and 26 days are shown as stages 1 to 4.

Based on quartiles of patients and degree of lung involvement from day 0 to day 26 after disease onset, four stages were identified from the onset of initial symptoms (Figure 3b): Stage-1 (0-4 days, n=24); Stage-2 (5-8 days, n=17); Stage-3 (9-13 days, n=21); and Stage-4 (≥14 days, n=20). In each group, the lower lobes were more inclined to be involved with higher CT scores. The CT scores of bilateral lower lobes were especially reaching significant differences than the corresponding upper/middle lobes in Stage-3 and Stage-4 (In Stage-3 and Stage-4, left lower lobe versus left upper lobe: 2 ± 1 vs. 1 ± 1, p=0.002, p=0.004, respectively; and right lower lobe versus right upper/middle lobe: 2 ± 1 versus 1 ± 1/1 ± 1, p<0.001/=0.002, p=0.001/0.003, respectively). In Stage-2, the total CT score was greater than that of Stage-1 (6±4 versus 2±2, p=0.002) (Table 2).

Table 2:

The CT score of the pulmonary involvement in four stages.

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The distribution of lesions and major CT findings were compared at the four stages of recovery (Table 3). Overal, subpleural lesions were more common than central lung lesions. The majority of patients had bilateral lung involvement during the course of the diease. In Stage-1, GGO [18/24 (75%) of patients] with partial crazy-paving pattern [6/24 (25%) of patients] and consolidation [10/24 (42%) of patients] could be mostly found (Figures 4, ​,5).5). In Stage-2, the GGO [14/17 (82%) of patients] extended to more pulmonary lobes with more crazy-paving pattern [9/17 (53%) of patients] and consolidation [8/17 (47%) of patients]. In Stage-3, consolidation [19/21 (91%) of patients] was the main demonstration with the obviously deceased ratio of GGO [15/21 (71%) of patients] and crazy-paving pattern [4/21 (19%) of patients]. In Stage-4, the consolidation [15/20 (75%) of patients] was partially absorbed without any crazy-paving pattern [0/20 (0%) of patients].

Table 3:

Distribution and frequency of the major of lung lesions on CT in different stages defined by the time of onset of symptoms.

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Figure 4:

Changes in the proportions of patients with GGO, crazy praving pattern and consolidation as a function of stage (stage definitions from Figure 3).

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Figure 5:

Typical evolution of CT findings in a47-year-old female patient presenting with persistent fever (38.8°C) for three days. (a) At presentation (day 3), a small region of subpleural GGO with partial consolidation was demonstrated in the right lower lobe; (b) day 7, there was an enlarged region of GGO with superimposed inter-and intralobular septal thickening (crazy-paving pattern) with partial consolidation; (c) day 11, partial resolution of the initial GGO, with a new area of subpleural consolidation; (d) day 20, continued resolution with minimal residual GGO and parenchymal bands were observed. All images have the same window level of -600 and window width of 1600.

Discussion

The purpose of this study was determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. We studied patients with COVID-19 at approximately 4 day intervals from the onset of disease until recovery. Patients with complicated pneumonia including severe respiratory distress (respiratory rate >30 breaths/min), requirement for oxygen treatment or mechanical ventilation or SpO2<90% on room air were excluded. In patients without severe respiratory disease, the major pulmonary CT findings of COVID-19 pneumonia were GGO, crazy-paving pattern and consolidation predominantly in subpleural locations in the lower lobes. Chest CT abnormalities increased in number and severity of lesions in the first 10 weeks (peaking at apprxoimately 10 days). Subseqquently, there was a short plateau phase and a gradual decrease in abnormalities.

In this study, the patients underwent multiple pulmonary CT scans (≥3 times) providing reliable data of the dynamic radiological pattern. The typical mild COVID-19 pneumonia mainly starts as small subpleural, unilateral or bilateral GGO in the lower lobes, which then develops into the crazy-paving pattern and subsequent consolidation. After more than two weeks, the lesions are gradually absorbed with residual GGO and subpleural parenchymal bands. In these patients who recovered from COVID- 19 pneumonia, 4 stages of lung involvement were defined on CT:

• 1. Early stage (0-4 days after onset of the initial symptom): In this stage, GGO was the main radiological demonstration (Figure 2a) distributed subpleurally in the lower lobes unilaterally or bilaterally. In our ochort, negative findings were revealed in four patients (total CT score=0) (Figure 3a). However, repeat pulmonary CT showed lung abnormalities in these 4 patients.

• 2. Progressive stage (5-8 days after the onset of the initial symptom): In this stage, the infection rapidly aggravated and extended to a bilateral multi-lobe distribution with diffuse GGO, crazy-paving pattern and consolidation (Figure 5b).

• 3. Peak stage (9-13 days after the onset of the initial symptom): In this stage, the involved area of the lungs slowly increased to the peak invovlment and dense consolidation became more prevalent. Findings included diffuse GGO, crazy-paving pattern, consolidation, and residual parenchymal bands.

• 4. Absorption stage (≥14 days after the onset of the initial symptom): In this stage, the infection was controlled and the consolidation was gradually absorbed. No crazy-paving pattern was present anymore. However, in this process, extensive GGO could be observed as the demonstration of the consolidation absorption (Figure 5d). Noticeably, in this study, no crazy-paving was observed in this stage, likely as a result of recovering. Based on the total CT score, the absorption stage extended beyond 26 days (our last days of follow-up) from the onset of initial symptoms.

Limitations of this study include the retrospective nature of our analysis and lack of a severe COVID- 19 comparison group. Most of the patients with severe pneumonia and ARDS are still hospitalized (17). Therefore, the analysis was limited to patients with mild COVID-19 pneumonia.

In summary, most patients who recovered from COVID-19 pneumonia showed greatest severity of lung disease on CT at approximately 10 days after initial onset of symptoms. Chest CT signs of improvment began at approximately 14 days after the onset of initial symptoms.

Acknowledgements

References