This study compared the temporal changes in CT manifestations between survivors and non- survivors with COVID-19. It demonstrated the pulmonary involvement of subpleural GGO and sequential consolidation gradually progressed reaching the peak after 20 days since symptom onset. Afterwards, the lesions started to be absorbed lasting for more than 40 days. In contrast, non-survivors demonstrated more rapid and persistent progression with more extensive bilateral lesions until ARDS occurred. Crazy-paving pattern was more predominant in non-survivors on admission compared with survivors.
In accordance with the previous studies, old patients (69 y, IQR: 63-78 y) with more comorbidities such as hypertension, diabetes, and coronary heart disease were more inclined to develop fatal ARDS [7, 23]. Initial symptoms were similar between survivor and non- survivor groups, whilst chest distress was more common in non-survivor group. Patients in non-survivor group underwent a progressive phase lasting for about 11 days which culminated in the development of ARDS. As a case-controlled study, the mortality rate of ARDS caused by COVID-19 could not be evaluated, but from a previous study, it was reported a mortality of 61.5% [24].
Initial laboratory investigations on admission showed multiple hematological and biochemical abnormalities which were significantly different between survivor and non-survivor groups. This can be attributed to the systematic inflammation reaction and pulmonary vascular endothelial damage caused by a severe viral infection, similar to the systemic response seen in other types of severe pneumonia [7, 21, 22, 24-26]. It has been postulated that COVID-19 could also damage T lymphocytes, thus, significant lymphopenia was probably a risk factor leading to the deterioration of patients' immune function and more rapid disease progression [7, 8, 24, 27]. In addition, the increased levels of CRP, lactate dehydrogenase, and D-dimer could also be indicators for development of ARDS, as reported in other types of pneumonia [20, 22, 25, 28].
In the early stage of COVID-19, subpleural GGO was the predominant finding [14, 17]. But in this study, patients were hospitalized after a median period of 8 and 9 days after the onset of symptoms in survivor and non-survivor groups, respectively, at which time the predominant findings in both groups corresponded with the progressive stage [14]. Thus, GGO was not the predominant finding in both groups but the consolidation and crazy-paving pattern. Compared with the survivors, it demonstrated the predominant CT demonstration of crazy-paving pattern in non-survivor group on admission was a major difference except for more diffuse and bilateral distributions. Pathologically, GGO may be an indicator of alveolar edema and proteinaceous exudates [29]. As the disease progresses, increasing alveolar edema, exudates and lymphocyte infiltrates fill the interstitial space leading to the radiological demonstration of diffuse “crazy-paving pattern” [19, 26, 30, 31]. Subsequent ARDS and potentially fatal respiratory failure developed as a result of diffuse alveolar edema with loss of alveolar epithelium [19, 31]. Thus, it was speculated large area of crazy-paving pattern was probably a CT indicator of poor prognosis.
Considering the heterogeneities of the scan time among the patients, longitudinal comparisons were not appropriate. Thus, the curve estimation was used to statistically compare the temporal evolution of the disease between two groups. Being different from the static comparison of chest CT on admission using the logistic module, curve estimation could analyze the dynamic patterns of the pulmonary involvement with time [16, 32]. Thus, it could provide a more composite comprehension of the time course in COVID-19 between survivors and non-survivors. As a result, it demonstrated a gradual resolution of abnormalities after a maximal total CT score of 6 at 20 days, longer than 10 days reported in the previous report [14]. It might be ascribed to a limited sample size in the previous study and more severe patients (15.7% of severe and critical patients) in survivor group. Thus, the previous study probably underestimated the recovery duration of COVID-19. Compared with survivor groups, the total CT score in non-survivor group demonstrated a more rapid increase in the first 10 days with a higher value of more than 10 points. Although the previous study showed the feasibility of making CT score as an indicator of prognosis, but it didn’t demonstrate the dynamic changes of CT score in the whole course [16]. In this study, it revealed the total score persistently elevated to a higher level close to 15 points without any decrease in non- survivor group, until the ARDS occurred with the following death events. From one pathological study in severe acute respiratory syndrome (SARS), it found the long duration of illness was resulted from the severe fibrosis and organization [26]. Considering the partial homology of SARS and COVID-19, it might explain why the lesions were rarely absorbed in non-survivors with COVID-19. This is another major difference between the two groups in the course, associated with the refractory feature of the critical COVID-19 under the present treatment protocols [13].
This study has limitations. Firstly, as a retrospective study, chest CT was used by the physician based on the clinical necessity and the status of the patient, so the heterogeneities of scanning time made it impossible to perform a conventional longitudinal comparison between two groups. Second, CT was not clinically feasible for patients after developing ARDS so not enough CT information was provided in the course of ARDS. Consequently, the majority of CT scans were performed in mild disease (363/436, 83.3%). To avoid data heterogeneity, the comparison of chest CT between two groups was only performed on admission due to the similar period from symptom onset and the curve estimation was used to evaluate the comprehensive trend of pulmonary involvement between two groups. Third, the multi-variate regression involving the CT, clinical, and laboratory parameters was not performed owing to the limited sample size with relatively a large number of parameters with significant differences between the two groups.
In summary, from comparisons between survivors and non-survivors, this study indicated that the presence of crazy-paving pattern on chest CT with the high and rapidly increased CT scores may help to identify the patients at high risk of developing ARDS before clinical deterioration. A larger, prospective study is required to confirm these findings with the more accurate quantitative assessment modality of the CT images in COVID-19.