Imaging-based indices combining disease severity and time from disease onset to predict COVID-19 mortality: A cohort study

Abstract

Background: COVID-19 prognostic factors include age, sex, comorbidities, laboratory and imaging findings, and time from symptom onset to seeking care.

Purpose: The study aim was to evaluate indices combining disease severity measures and time from disease onset to predict mortality of COVID-19 patients admitted to the emergency department (ED).

Materials and methods: All consecutive COVID-19 patients who underwent both computed tomography (CT) and chest X-ray (CXR) at ED presentation between 27/02/2020 and 13/03/2020 were included. CT visual score of disease extension and CXR Radiographic Assessment of Lung Edema (RALE) score were collected. The CT- and CXR-based scores, C-reactive protein (CRP), and oxygen saturation levels (sO2) were separately combined with time from symptom onset to ED presentation to obtain severity/time indices. Multivariable regression age- and sex-adjusted models without and with severity/time indices were compared. For CXR-RALE, the models were tested in a validation cohort.

Results: Of the 308 included patients, 55 (17.9%) died. In multivariable logistic age- and sex-adjusted models for death at 30 days, severity/time indices showed good discrimination ability, higher for imaging than for laboratory measures (AUCCT = 0.92, AUCCXR = 0.90, AUCCRP = 0.88, AUCsO2 = 0.88). AUCCXR was lower in the validation cohort (0.79). The models including severity/time indices performed slightly better than models including measures of disease severity not combined with time and those including the Charlson Comorbidity Index, except for CRP-based models.

Conclusion: Time from symptom onset to ED admission is a strong prognostic factor and provides added value to the interpretation of imaging and laboratory findings at ED presentation.

Fig 1. Flowchart representing patient inclusion.

Fig 2. Example of RALE scores and respective CT.

Examples of Radiographic Assessment of Lung Edema (RALE) on chest X-rays (CXR) which were divided into quadrants (A, B, C) and correlation with coronal reconstruction of chest computed tomography (CT) performed within 24 hours (D, E, F). Patient 1 (male, 37 y/o) was attributed a RALE score of 7 because of the presence of moderate alveolar opacities in 50/75% of the right inferior quadrant and hazy alveolar opacities in < 25% of the left inferior quadrant (A); chest CT demonstrated the presence of GGO in the right lower lobe and a small area of GGO in the left lower lobe (visual score 10%) (D). Patient 2 (male, 53 y/o) had a RALE score of 19 due to dense alveolar opacities in > 75% of the right lower quadrant, moderate alveolar opacities in 50/75% of the left lower quadrant, and hazy alveolar opacities in < 25% of the left upper quadrant (B); chest CT demonstrated the presence of extensive parenchymal consolidation of the left lower lobe and small areas of GGO in the right lung (visual score 30%) (E). Patient 3 (male, 45 y/o) was attributed a RALE score of 36 because of the involvement of > 75% of every quadrant, with dense opacities in the left lower quadrant and moderate opacities in the remaining three quadrants (C); chest CT demonstrated bilateral consolidations (visual score 60%) (F).

Fig 3. ROC curves.

Receiver operating characteristic (ROC) curves of each measure of disease severity (red line) and respective severity/time index (blue line) in multivariable logistic models for death at 30 days, adjusted for age and sex. Considered measures of disease severity are computed tomography (CT) visual score of disease extension (panel A), chest X-rays (CXR) Radiographic Assessment of Lung Edema (RALE) score (panel B), CRP levels (panel C), and sO₂ levels (panel D). Horizontal axis: 1—Specificity from 0 to 1.00; vertical axis: Sensitivity from 0 to 1.00.