Correlation analysis between CT findings and duration of initial symptoms in young and middle-aged patients with novel coronavirus pneumonia

Objective: To retrospectively analyze the correlation between CT findings and duration of initial symptoms in young and middle-aged patients with novel coronavirus pneumonia. Materials and methods: From January 17, 2020 to February 4, 2020, of the 54 SARS-COV-2 infection cases, 48 cases (48/54,88.8%) were young and middle-aged patients under 60 years old. Finally, thirty-three patients under 60 years old with CT imaging were enrolled in this study, including 20 men and 13 women. Patients’ clinical data, including gender, age, infection exposure history, heating temperature, the initial symptoms and the duration, were recorded. The CT imaging features of pneumonia was scored. The number of lung lobe involvement and the length of the largest lesion were recorded. All above CT findings and clinical data were evaluated. Results: The median duration of initial symptoms was 3 days (range 0-7 days). The CT score and the length of the largest lesion showed statistically significant between the groups of initial symptom duration < 3 days and initial symptom duration ≥3 days (P<0.05). while age, gender, infection exposure history, fever temperature and the number of affected pulmonary lobes between the two groups had no significant difference (P>0.05). The duration of the initial symptom was positively correlated with both the CT score of pneumonia (r=0.502, P=0.003) and the length of the largest pneumonia lesion in the lung (r=0.506, P=0.003). Conclusion: The severity of pneumonia and the size of lesions were positively correlated with the duration of the initial symptom in young and middle-aged patients.


Introduction
In December 2019, a group of patients with unknown cause pneumonia were found to be linked to a seafood wholesale market in Wuhan, China. The emergence of the infectious pneumonia caused great concern. Through whole-genome sequencing of pneumonia patients, a previously unknown novel coronavirus was discovered, which was soon identified by the world health organization (WHO) as the virus responsible for the outbreak and tentatively named 2019-nCOV (1,2). phylogenetic analysis suggests that bats might be the original host of this virus. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans (3). The novel coronavirus was then officially named "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-COV-2), and the disease caused by the coronavirus was identified as "Corona Virus Disease 2019" .
Some studies showed that the common symptoms at onset included fever, cough and myalgia or fatigue, and the less common symptoms included phlegm, headache, hemoptysis and diarrhea. In addition, the chest imaging examination demonstrated inflammatory changes, and some patients have underlying diseases, including diabetes, hypertension and cardiovascular diseases (4). To the best of our knowledge, study of pulmonary inflammatory lesions imaging findings in the novel coronavirus pneumonia patients is not much. Disease progression is associated with patient physical condition, and the elderly patients or the patients with underlying disease may increase susceptibility to novel coronavirus, speed up the progress of the disease, while young and middle-aged patients under 60 years old have few basic diseases and few pulmonary lesions. In this study, we aimed to analyze the correlation between CT findings and the duration of initial symptoms in young and middle-aged patients with novel coronavirus pneumonia. Our study may reveal the correlation of the pneumonia CT manifestations and course of the disease, and provide valuable information for pulmonary lesion changes of young and middle-aged COVID-19 patients with different duration of initial symptoms. patients were finally included in the study (Figure 1), including 20 males and 13 females.

Materials And Methods
All patients' clinical data, including gender, age, history of infection exposure, fever temperature, initial symptoms and the duration, were recorded.

2.CT examination and image evaluation
The CT scans was performed in the 33 patients without administration of contrast material. 17 patients from the first affiliated hospital of Wenzhou medical university and as consolidation (7). The affected lung parenchyma was assigned to the following score according to lobes (each patient had a total of five lobes) and the extent of involvement: 0 as none, 1 as < 5%, 2 as 5-25%, 3 as 25-50%, 4 as 50-75%, and 5 as > 75%. The CT scan was reviewed on the cross-sectional image. The five-point scale of the lung parenchyma distribution was then multiplied by the CT findings of pneumonia scale described above.
Scores from all regions were added to obtain the final total cumulative score, with CT scores ranging from 0 to 50 (8). The number of affected pulmonary lobes and the length of the largest lesion were also recorded.

3.Statistical analysis
SPSS 24.0 software was used for statistical analysis. The continuous variables were expressed as mean ± standard deviation (SD), or median and range, and the categoric variables as a number of individuals with percentage in each group. The comparisons of continuous variables between groups were performed using the Mann-Whitney U test.
Frequencies of categoric variables were compared using the Fisher exact test. The spearman correlation analysis was used to investigate the correlation between the CT score of pulmonary inflammatory lesions and the duration of initial symptoms, as well as the correlation between the length of the largest inflammatory lesions in the lungs. p values < 0.05 were considered statistically significant. Lung lesions in CT characterized by multiple in the lung, the regional or scattered inflammatory opacity, CT finding showed the opacity as small patch ground-glass attenuation and may with interstitial changes, or consolidation of the lung, the pathological changes in the lung periphery. From the CT images, we observed that there were 3 patients (9.1%) with normal CT manifestations, 19 patients (57.6%) with dominated ground glass opacity, and 11 patients (33%) with consolidation or dominated consolidation surrounded by ground glass opacity ( Figure 2). The mean CT score was 5.61±4.83 points.

Results
The mean length of the maximum inflammatory lesion in the lung was 26.00±17.62 mm.
The median number of involved lobar was 3. None lobe was involved in 4 patients ( According to the median duration of initial symptoms, patients were divided into two groups: initial symptom duration < 3 days and initial symptom duration ≥3 days. The results showed that CT scores and length of the maximum inflammatory lesion between the two groups were statistically different (P < 0.05), while age, gender, infection exposure history, fever temperature and the number of affected pulmonary lobes between the two groups had no significant difference (table 1).

Correlation analysis
Spearman correlation analysis showed that there was a positive correlation between the duration of the initial symptom and the CT score of lung lesions; the longer the duration of the initial symptom was, the more serious the CT manifestations of lung lesions was. The duration of the initial symptom was also positively correlated with the length of the largest inflammatory lesion in the lung; the longer the duration of the initial symptom was, the larger the lesion was (table 2).

Discussion A novel coronavirus (SARS-COV-2) pneumonia caused multiple infections in the central
Chinese city, Wuhan, and it has been shown to have human-to-human transmission and sustained human-to-human transmission characteristic, which is a new risk to public health. Although the time between the onset of the disease and seeking medical attention is now generally shorter, with 27% of patients seeking medical attention within two days of onset, but at least 89% of patients are not hospitalized until the fifth day of illness (9).
Because pneumonia is the common characteristic of SARS-COV-2 infection, and it is a concern that the course of disease development of pneumonia in COVID-19 patients.
Applying anomalies has also been demonstrated when chest radiographs show normal or only suspicious anomalies (16,17). In this study, CT examination of COVID-19 patients showed that the lesions were mostly located in the peripheral pulmonary zone and were presented as localized or multiple patchy ground glass opacity or solid lesions. Since the viral infection was mainly interstitial lesions, there was no trend of pulmonary segments and subsegment distribution. Other studies (12) suggested that there was no significant difference in lobar or craniocaudal distribution of the novel coronavirus pneumonia.
CT findings of pulmonary inflammatory are related to the development of inflammatory pathology. In the early stage of the disease, localized inflammatory infiltration of both sides of the lungs was commonly observed, which was the most of ground glass opacity under the pleura. The early stage lung tissues showed different degree of alveolar injury, including alveolar congestion, inflammatory exudation and formation of hyaline membrane (18). Therefore, the CT manifestations showed thin ground glass opacity, and crazy-paving pattern or reticulation changes were formed when the lesions accompanied by pulmonary interstitial edema. The main CT manifestations in the progressive stage were increased number of lesions and expanded range, gradually involving multiple lobes in lung, and consolidation or co-existence of consolidation and ground glass opacity. Irregular consolidation is often associated with a large number of exfoliated epithelium and foam cells in the alveoli, inflammatory cell infiltration, inflammatory exudation filling the alveolar cavity. Consolidation tissues may be accompanied by capillary congestion and necrosis of lung tissue and alveoli (19). After the onset of initial symptom, the pulmonary lesions gradually developed from normal or blurred ground glass opacity to solid opacity.
The CT score showed that the overall pulmonary inflammatory lesions increased after the duration of initial symptom increased, and CT scores were higher in the group of initial symptom duration ≥3 days. The longer the duration of the initial symptom was, the more pneumonia infiltration and expansion will occur, and the more consolidation changes will occur.
The main symptom of SARS patients included fever, general discomfort, muscle pain, fatigue and head ache, and some patients in the acute phase might had viremia (20). The main symptom of COVID-19 patients was fever. In this study 60.6% of the patients had initial symptoms of fever. Other initial symptoms included diarrhea or a sore throat, etc.
The correlation analysis showed that the duration of initial symptoms of patients was positively correlated with the CT score of pulmonary inflammatory lesions. The initial symptom duration of pneumonia may be used to evaluate disease progress, and it was associated with the size of the largest lesions. Therefore, patients with fever or other symptoms should be paid attention to. In this study, it was suggested that most of the lung lesions were blurred ground glass opacity dominated within 7 days after the initial symptoms, accounting for 57.6%. The inflammatory lesions were relatively mild, while main consolidation or multiple consolidation accompanied by ground glass opacity accounted for 1/3. Gaik et al. (21) showed that within the 1st week after onset of the initial symptoms, the more pulmonary lesions will progress, so early treatment is of great importance for patients to control the disease.
There were several limitations in our study. First, this was a retrospective study and the number of patients enrolled was small. Only 33 young and middle-aged COVID-19 patients with CT imaging. We limited our study to chest CT, because CT was more sensitive to early or mild disease. However, in medical front lines, chest radiography may also serve as a screening tool in areas with high disease prevalence and limited resources. Second, the study was only conducted during early and mild stage, and study in the acute phase of SARS-COV-2 was missed. It is necessary to further study the imaging manifestations of severe or treated patients in the future to enrich the imaging studies of SARS-COV-2.
In conclusion, we revealed a potential positive correlation between the duration of the initial symptoms and the degree and size of pneumonia lesions. Most of the early lesions were ground glass opacity.     Chest plain CT imaging of the patients. (A-C) Case 1, male, 50 years old, has a history of infection exposure, fever for one day, CT finding was multiple round ground glass opacity, and CT score was 5. (D-F) Case 2, male, 50 years old, has no history of infection exposure, fever for 2 days, CT finding showed multiple subpleural ground glass opacity, and CT score was 6 points. (G-I) Case 3, male, 46 years old, has a history of infection exposure, sore throat for 7 days, fever for