In this study, we developed and validated a radiomics nomogram based on the quantitation of lung abnormalities on CT images caused by COVID-19 to identify the severe patients for guiding a prompt management and treatment. The radiomics nomogram incorporates three items of the radiomics signature, comorbidity and abnormal WBC counts. The radiomics signature successfully stratified patients according to their clinical conditions (severe or none-severe). The use of multi-task Unet network, which could segment the lesion or lung abnormalities related to COVID-19 automatically, increased the potential value of the radiomics nomogram in evaluating the clinical condition of patients with COVID-19.
Previous studies [18, 19, 24] have demonstrated that CT-based radiomics as a superior tool for screening potential new cases of COVID-19, and had a good prediction on discriminating COVID-19 and non-COVID-19 pneumonia or other types of viral pneumonia. Mei et al. [24] used CT-based radiomics achieved an AUC of 0.92 and had equal sensitivity as compared to a senior radiologist when applied to a group of 279 cases, CT-based radiomics can be severed as a rapid method for screening COVID-19 patients. Huang et al. [19] summarized 154 patients with viral pneumonia (including 65 cases of influenza pneumonia and 89 cases of COVID-19) to develop a CT-based radiomics model, the results showed radiomics model had a satisfactory performance in distinguishing influenza pneumonia and COVID-19. Nevertheless, it is of great necessity to assess the severity of patients with COVID-19 before treatment, which may greatly determine the clinical prognosis. We firstly assessed the lung abnormalities associated with COVID-19 by quantitative analysis, and then developed and validated a radiomics signature to identify severe COVID-19 patients. The results in present study uncovered that the radiomics signature could get a better performance in discriminating the severity of COVID-19 patients with an AUC of 0.943 in primary cohort, which was then further confirmed in validation cohort with an AUC of 0.941. Thus, the radiomics signature was effective for identification of none-severe and severe type COVID-19 patients. Notably, when combined with clinical risk factors including comorbidity and abnormal WBC counts, the discrimination potency was improved with an AUC of 0.972 and 0.978 in the primary and validation cohorts, respectively. Thus, we think that the noninvasive radiomics signature, which makes the most of the chest CT images, may serve as a practical method for identification of none-severe and severe type COVID-19 patients.
The radiomics signature includes four parameters of pleural thickening, total volume of the lesion, ratio of consolidation volume to whole lung volume and ratio of lesion volume to whole lung volume, which were obtained automatically by computer-aided system or Multi-task Unet network. Presently, COVID-19 has reached the stage of a pandemic, which contributed to an extreme shortage of clinicians and radiologists. The application of artificial intelligence technology or computer-aided system, a noninvasive, fast, reproducible technique, to assess the COVID-19 could alleviate the insufficiency of radiologists to some extent. Furthermore, patients with COVID-19 would benefit from a timely and accurate assessment of the severity through radiomics signature before getting a prompt and proper treatment.
It is unexpected that increased total volume of the lesion, ratio of consolidation volume to whole lung volume and ratio of lesion volume to whole lung volume, are associated with severe COVID-19 patients. The more extensive involvement of lung parenchymal, the more severe condition it would be. The appearance of GGO indicates that alveolar cavity is partially filled by fluid and cells to the layer against the alveolar walls[25], while the consolidation sign demonstrates that the disease progresses due to further accumulation of exudates in alveolar cavity and aggravation of interstitial edema [25]. The chest CT features of COVID-19 are manifested as multiple patchy GGOs with or without consolidation distributed in subpleural areas of bilateral lungs [15]. When the volume of consolidation increases, more alveolar cavities are filled completely with exudates, resulting in dysfunction of oxygen exchange and oxygenation. Then, a respiratory failure occurs, which is presented as a severe condition. Above all, our study quantified the lesion of GGO and consolidation to investigate its value in identification of severe patients with COVID-19, and to build a useful radiomics signature for clinicians.
Additionally, clinical features including comorbidity and abnormal WBC counts were independent risk factors contributing to worse clinical condition of patients with COVID-19. According to a previous study, presence of comorbidity is an essential factor in determining the prognosis of several diseases, especially pneumonia [26]. Therefore, we also has taken comorbidity into consideration in the present study and found a positive correlation with the severity of COVID-19, which was consistent with the previously study [27]. CRP is an important inflammatory index. Although a significant difference in CRP increase was indicated by univariate analysis in primary and validation cohorts, it was not an independent predictor for identification of clinical condition of COVID-19 in this study. The main reasons may be that 1) CRP is a common signal for responding to inflammation; 2) the change of CRP is analyzed as a categorical variable, which may lead a bias to subtle difference. Moreover, Viral infections in the human body primarily involve damage to the immune system, which presents as decrease in the absolute number of lymphocytes and leukocyte [28]. In this study, we found that leukocyte and lymphocytes differed between severe and none severe patients with COVID-19, which is consistent with the study of Wang D et al [27]. In addition, WBC (leukocyte) is an independent predictor for identification of clinical condition of COVID-19. Interestingly, 9 severe patients presented with an increased WBC counts, which may be ascribed to other infections, such as bacterium. Comprehensively, a severe and critical patient with COVID-19 may be caused by cytokine storm, comorbidity with various infections (9 patients with increased WBC counts) and immune dysfunction. In a word, incorporating clinical features into radiomics nomogram could improve its diagnostic value of none-severe and severe cases with COVID-19.
The most important application of the radiomics nomogram is to guide management and treatment of patients with COVID-19, especially for severe type cases who need additional treatment or care. According to recent reports and recommendations, severe patients with COVID-19 need hospitalized therapy. Besides antiviral therapy, some additional treatment should be added for severe patients [27, 29]. To block cytokine storm, a blood-purifying therapy including plasmapheresis, hemoperfusion is recommended, which can reduce the damage of inflammatory reaction to the body or lung [7]. If possible, convalescent plasma therapy could be a preferred scheme for treatment of severe patients [7]. Using the nomogram, we can quickly and precisely identify the none-severe and severe patients with COVID-19, and prompt a timely additional treatment and care to improve prognosis. On the other hand, COVID-19 is a dynamic disease [14, 30], a quantitative radiomics nomogram is helpful to follow up the changes of patients after treatment. To justify the clinical practicability of radiomics nomogram, decision curve analysis was applied in this study. This novel method offers an insight into clinical consequences based on threshold probability, from which the net benefit could be derived (Net benefit is defined as the proportion of true positives minus the proportion of false positives, weighted by the relative harm of false-positive and false-negative results). The decision curve in our study showed that if the threshold probability of a patient was more than 3%, using the radiomics nomogram to identify none-severe or severe patients added more benefit than either treat all as severe patients or none-severe patients.
Admittedly, our study has several limitations. The sample size in our cohort is relatively small. The relationship of radiomics to prognosis has not been studied due to time limitation. Thus, a further study with more cases and prolonged period should be conducted in the future.