Our systematic review and meta-analysis of 18 studies involving 3323 patients provides comprehensive information on the chest CT features associated with the severe cases of COVID-19 infection. Bronchial wall thickening was more likely to be associated with severe cases of COVID-19 infection, followed by linear opacity, and GGO. However, there was no significant association between the presence of consolidation and severity of clinical presentation. Considering the lesion distribution, as expected, bilateral lung involvement was more frequently associated with severe clinical presentation.
GGO indicates an area of hazy increased lung opacity, less opaque than consolidation, through which vessels and bronchial structures may still be obscured. Although GGO is the most common CT feature of COVID-19 pneumonia, most studies did find no statistically significant difference in the presence of GGO between severe and common cases of COVID-19. Nevertheless, the meta-analysis of these studies indicated a 37% increase in the risk of the presence of GGO in severe cases compared to the common type (Figure 2). Since the GGO has been known as the typical early CT feature of COVID-19 pneumonia, it is advised that the small lesions, and especially new lesions, that contained an area of GGO requires follow-up to eliminate the possibility of COVID-19 pneumonia in high-risk subjects (21).
Consolidation is often a middle-to-late stage feature in pulmonary infection. Although some studies indicated the association of consolidation with the severity of COVID-19 infection, others failed to show this association. The pooled analysis of these studies did not demonstrate any significant association between the presence of consolidation and the severity of clinical manifestations (Figure 3). Consolidated tissue is more radio-opaque than normally aerated lung parenchyma, indicating the alveoli are completely filled by inflammatory exudation, hemorrhage, or pus. This feature could reflect the severity of lung involvement. The reason why this meta-analysis could not find a significant association between the presence of consolidation in the chest CT and severity of clinical presentation might be explained by the fact that in the included studies the chest CT scan had been performed at the early stage of the infection while consolidation has been demonstrated to be noted on chest CT during disease progression (3). Thus, the time point from the onset of disease at which the chest CT is performed has a critical role in demonstrating the consolidation.
The linear opacity, occurred in different interstitial lung disease, is typical for an evolution towards organizing pneumonia. Pooled analysis of studies evaluated the presence of linear opacity among patients with various disease severities indicated this finding is more likely to be observed in severe cases of COVID-19 than that observed in the common type (Figure 4). Temporal analyzing of multiple chest CT scans demonstrated a specific pattern during which linear opacity, observed 7–31 days after disease onset, indicates sub-segmental atelectasis or secondary organizing pneumonia. This pattern might be representative of irreversible fibrosis (21, 22).
Bronchial wall thickening
Abnormal thickening of bronchial walls, arisen from various pathological entities, usually indicates inflammation of the airways. A few studies investigated the association of bronchial wall thickening with the severity of COVID-19 infection, resulting in the conflicting findings. Pooled analysis of these findings indicated significantly higher odds of bronchial wall thickening in severe cases of COVID-19 compared to the common type (Figure 5). Airway wall thickening, which has been attributed to the high level of Vascular endothelial growth factor (VEGF), is suggested to reflect the duration and severity of disease and the degree of airflow obstruction in asthma (23, 24). On the other hand, recent evidence has revealed an increase in the levels of VEGF in COVID-19 patients (25), leading to the use of anti- VEGF medications in severe cases of COVID-19 infection in the context of clinical trial (https://clinicaltrials.gov/ct2/show/NCT04275414). The association of bronchial wall thickening with the severity of COVID-19 infection in this meta-analysis could be explained by the possible role of VEGF in the development and severity of bronchial wall thickening in COVID-19.
Bilateral lung involvement
Many studies investigated the distribution of lung involvement in patients with various severity indicating the conflicting results. However, analysis of the pooled data showed bilateral lung involvement is 3.44 times more likely to be observed in severe cases of COVID-19 compared to the common type (Figure 6). Irrespective of the disease severity, some previous studies indicated that bilateral lung involvement is the most anatomic distribution of COVID-19 pneumonia (26, 27).
Strength and Limitation
To the best of our knowledge, this meta-analysis is the first one that evaluated chest CT features associated with clinical severity of COVID-19 infection. Moreover, high quality studies with a relatively large number of participants have been included in this study. In addition, all studies included in this meta-analysis followed the same classification for determination of disease severity.
However, this study has several limitations. First of all some features of chest CT imaging have not been included in the meta-analysis. Furthermore, some patients might have comorbidities such as chronic obstructive pulmonary disease (COPD) that could affect imaging appearance. Moreover, all included studies were retrospective that the results might be influenced by the confounding factors. In addition, because of different CT scanners and interpreting radiologists, the reported imaging features might be variable across sites. Lastly, this meta‐analysis indicated a significant heterogeneity between the studies regarding some CT features. Moreover, results on GGO might be affected by the publication bias.