The Institutional Review Board (Comitato Etico di Bergamo, Italy) approved this retrospective observational study and waived the written informed consent.
A total of 359 consecutive patients presenting to the EDs of two affiliated hospitals (Papa Giovanni XXIII and San Giovanni Bianco, Bergamo, Italy) between March 1 and 13, 2020, were considered eligible for inclusion. The inclusion criteria were the following: (a) initial CXR performed in the ED setting and (b) final diagnosis of COVID-19 confirmed by a positive RT-PCR test. The exclusion criteria were (a) unavailable clinical or laboratory data (n = 5) and (b) non-diagnostic CXR image quality (n = 14). Finally, a total of 340 patients were retrospectively enrolled.
Demographic, clinical, and laboratory data were collected from patients’ medical records. The recorded data included the following: age, sex, medical comorbidities, symptoms, clinical and laboratory data within 24 h of ED presentation (including the oxygen saturation [SpO2], fraction of inspired oxygen [FiO2], arterial partial pressure of oxygen [PaO2], and PaO2/FiO2 ratio), and mode of respiratory support (oxygen mask, continuous positive airway pressure/noninvasive mechanical ventilation, invasive mechanical ventilation). For patients admitted to the intensive care unit, the highest levels of positive end-expiratory pressure, the use of extracorporeal membrane oxygenation, and prone positioning were also recorded. Patient length of stay was calculated by subtracting the date of ED presentation from the date of discharge or death. Patient survival status, as well as the date of death, was obtained from the Regional Healthcare Information System (SISS, Regione Lombardia, Italy) as of May 12, 2020.
Imaging acquisition and analysis
Images were acquired using digital radiographic systems (Definium 8000, GE Healthcare; FDR AcSelerate, Fujifilm Corporation) with tube voltages ranging from 120 to 150 kVp and by employing automatic exposure control. The imaging data included CXR images acquired in the posteroanterior and lateral (PA/LAT, n = 130) or anteroposterior (AP, n = 210) projections. The latter was performed when the patient was too unwell to tolerate standing. Only the AP and PA images were selected and retrospectively evaluated by two reviewers (G.M., a thoracic radiologist with 5 years of experience in a referral center; M.B., a fourth-year radiology resident), blinded to patient history other than COVID-19 positivity. Reviewers independently assessed the presence of lung abnormalities, including ground-glass opacities (GGOs), consolidation, and pulmonary nodules . Distribution of GGOs and consolidation was classified as follows: (a) peripheral (involving mainly the peripheral one-third of the lung), central (involving mainly the central two-thirds of the lung), or neither; (b) unilateral or bilateral; (c) upper zone (above the inferior wall of the aortic arch), middle zone (between the inferior wall of the aortic arch and the right inferior pulmonary vein), lower zone (below the right inferior pulmonary vein), or no zonal predominance. The presence of pleural effusion was assessed. The two reviewers were also asked to grade each CXR using the Brixia scoring system, an experimental 18-points severity scoring system designed for the assessment of COVID-19 pneumonia . The Brixia score is obtained by dividing each lung into 3 zones (upper, middle, and lower zone, as explained above) and then scoring each zone from 0 to 3 based on types of pulmonary infiltrates detected, as follows: 0, no lung abnormalities; 1, interstitial infiltrates; 2, interstitial and alveolar infiltrates (interstitial predominance); 3, interstitial and alveolar infiltrates (alveolar predominance). The terms “interstitial infiltrate” and “alveolar infiltrate” used in the Brixia scoring system were reported in the current study as GGO and consolidation, respectively. CXRs showing only abnormalities other than GGOs and consolidation were scored as 0. Pure consolidation was scored as 3. The number of zones involved was also recorded. In addition, the overall extent of GGOs and consolidation was assessed by visually estimating and then averaging the percentage of involvement within each lung.
Patient data and CXR findings were reported as median and interquartile range (IQR) in case of continuous variables, or numbers and frequency distribution (%) in case of binary or categorical variables.
CXR findings’ inter-rater agreement was assessed both in the whole group and in subgroups with AP and PA radiographs by weighted Cohen’s kappa (categorical variables), or intraclass correlation coefficient (ICC) (quantitative variables, namely the number of lung zones involved, Brixia score, and percentage of lung involvement). Moreover, the agreement in Brixia score and percentage of lung involvement was visualized by correlation and Bland-Altman plots.
Predictors of death and mode of respiratory support were identified among age, sex, comorbidities, duration of symptoms, SpO2, and PaO2/FiO2 ratio, as well as CXR findings (laterality, type of parenchymal opacity, number of lung zones involved, Brixia score, and percentage of lung involvement), by logistic and ordinal logistic regression, respectively. In all cases, univariate analyses were first performed to identify possible predictors. All variables with significant contributions at univariate analysis were included in the multivariate analysis, and main predictors were finally identified by reducing the multivariate model using a stepwise model selection technique. CXR findings refer to the most experienced reviewer, and only patients with no missing data were included in the regression analyses.
Significance of the differences in demographic, clinical, and laboratory data between patients with mild (Brixia score < 8) and severe (Brixia score ≥ 8) CXR findings was assessed by two-tail independent t test (continuous variables) or chi-squared test (binary and categorical variables). Significance of the differences in the demographic, clinical, laboratory, and radiological features between deceased and survived patients was assessed by the Mann-Whitney test (numerical variables) or chi-squared test (binary and categorical variables).
Survival curves and pertinent 95% confidence intervals were computed using the Kaplan-Meier method for the whole patient cohort as well as for patients grouped by individual grouping variables (age, sex, number of comorbidities, PaO2/FiO2 ratio, CXR findings at ED presentation). The significance of the difference between strata was computed by log-rank test. The distribution by the most invasive respiratory support employed of age, PaO2/FiO2 ratio, Brixia score, percentage of lung involvement, and number of lung zones involved was displayed by boxplots.
In all tests, statistical significance was set at p < 0.05. All statistical analyses were performed using R software, version 3.6.3.