Study design and participants
This research consisted of a retrospective single-center study at the Central Hospital of Wuhan. The study was approved (Approval No. 2020421) by the Central Hospital of Wuhan Ethics Committee; the requirement for written informed consent was waived by the Ethics Commission of the designated hospital based on the exigencies associated with emerging infectious diseases.
This study consecutively enrolled all patients at the Central Hospital of Wuhan who were diagnosed with COVID-19, based on WHO interim guidelines, between December 25, 2019, to February 16, 2020 . The study design protocol was finalized before the initiation of data collection and parts of the patients have been included in our recent report . Based on the new coronavirus pneumonia diagnosis and treatment protocols (version 6) developed by the National Health Commission of the People’s Republic of China (http://www.nhc.gov.cn/), the clinical classification of COVID-19 was stratified as follows: moderate-type cases included individuals with fever, respiratory tract involvement, and other symptoms, as well as imaging findings of pneumonia; severe-type cases additionally met any of the following criteria: (1) respiratory distress with a respiratory rate ≥ 30 beats/min; (2) oxygen saturation ≤ 93% at rest; and (3) arterial blood oxygen partial pressure (PaO2)/oxygen concentration (FiO2) ≤ 300 mmHg (1 mmHg = 0.133 kPa); critical-type cases additionally exhibited any of the following conditions: (1) respiratory failure requiring mechanical ventilation; (2) shock; (3) intensive care unit (ICU) admission for combined organ failure.
Inclusion and exclusion criteria
Inclusion criteria were as follows: (1) diagnosis of COVID-19 based on exposure history or based on clinically compatible symptoms; (2) classification on admission as moderate type, according to protocols (version 6) developed by the National Health Commission of the People’s Republic of China; and (3) recovery during the study period. Exclusion criteria were as follows: (1) patient was still hospitalized at the end of follow-up; (2) patient transferred to another medical institution; (3) diagnosis not confirmed by repeated tests for the presence of SARS-CoV-2 RNA; (4) fatality; (5) patient diagnosed with severe-type or critical-type COVID-19 on admission; (6) incomplete medical records; or (7) case records lacked a second chest computed tomography (CT) scan.
Epidemiological, clinical, laboratory, and radiological characteristics, as well as outcome data, were extracted from electronic medical records. The data were reviewed by two physicians, and a third physician adjudicated any differences in interpretation between the two primary researchers. Fever was defined as axillary temperature higher than 37.3 °C. Epidemiological, clinical, and laboratory data were defined as the results of the first consultation or examination in the electronic medical records. The initial chest CT was defined as the first chest CT examination at or following admission.
CT acquisition and evaluation
Chest CT scans were performed with the patient in a supine position and using a single inspiratory phase on one of the four CT systems available at our facility. These machines included the following equipment: Bright Speed Elite (GE, America); Philips Ingenuity Core128 (Philips Medical Systems, Best, the Netherlands); uCT 760 (United Imaging, China); and SOMATOM Definition AS (Siemens Healthineers, Germany). The following primary settings were used: tube voltage, 120 kVp; automatic tube current modulation (20-130 mAs); matrix, 512×512; field of view (FOV), 350 mm × 350 mm - 370 mm × 370 mm; pitch, 0.75-1.25 mm; and slice thickness, 1-1.5 mm. The reconstructed images were sent automatically to the corresponding post-processing workstation and Picture Archiving and Communication Systems (PACS) for multiplanar reconstruction post-processing. All chest CT images were analyzed independently, and the features were scored by a senior thoracic radiologist with more than 20 years of experience who was blinded to clinical and laboratory findings. A previously described semi-quantitative scoring system was used to estimate the pulmonary involvement of lesions on the basis of the area involved . Briefly, each of the 5 lung lobes was visually scored from 0 to 5, as follows: 0, no involvement; 1, <5% area involvement; 2, 5%-25% area involvement; 3, 26%-49% area involvement; 4, 50%-75% area involvement; and 5, >75% area involvement. The total CT score was calculated as the sum of the scores for the 5 lung lobes in a given case, yielding a value that ranged from 0-25. All CT scans acquired after the development of severe disease were excluded.
After admission, patients were subjected to re-examination by performing a second chest CT scan. Serial chest CT scans were performed based on the hospital’s clinical decision policy. The primary endpoint of the present study was the development of severe/critical illness. The secondary endpoint was recovery from COVID-19.
Continuous variables are presented as mean ± SD or median with interquartile range (IQR), depending on the normality of distribution. Categorical variables are presented as frequencies and percentages. Continuous variables were compared between the moderate-type group and the severe/critical-type group using a non-paired Student’s t-test or Mann-Whitney U test. Categorical variables were compared using a chi-squared test or Fisher’s exact test, as appropriate. Univariable and multivariable logistic regression models were used to explore the risk factors associated with progression from moderate-type symptoms to severe/critical-type symptoms. Considering the total number of severe/critical-type cases (n=40) in the present study, and to avoid overfitting in the model, we excluded variables if any of the following conditions applied: between-group differences in variables were not significant; variable accuracy was unconfirmed (e.g., surgery history, which was self-reported); number of events was too small to calculate an odds ratio; or variables exhibited collinearity with the maximum CT score. Using the new coronavirus pneumonia diagnosis protocols as the standard of reference, diagnostic performance with the highest CT score of cases that progressed to severe/critical type was determined using analyses of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC). The 95% confidence intervals (CIs) also were reported. Diagnostic ability was illustrated using a receiver operating characteristic curve (ROC). A two-tailed p < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS, version 18 (SPSS, Inc., Chicago, IL).