In the XXXXX province (XXXXX, 532,000 inhabitants, six hospitals), the first case of SARS-CoV-2 infection was diagnosed on February 27, 2020. Up to March 24, 2020, there were 1399 RT-PCR-confirmed COVID-19 cases and the daily number of new cases was still rising.
Study design and population
This observational study was approved by the Area Vasta Emilia Nord Ethics Committee on April 7, 2020 (protocol number 2020/0045199). Patients’ informed consent to participate in the study was obtained whenever possible, given the retrospective nature of the study. We included all consecutive patients who presented to the provincial emergency rooms (ERs) between February 27 and March 23, 2020 for suspected COVID-19, underwent chest CT at ER presentation, and were positive on RT-PCR for SARS-CoV-2 within 10 days from ER presentation.
During the COVID-19 outbreak, the diagnostic protocol for suspected COVID-19 patients presenting to the ER included nasopharyngeal/oropharyngeal swabs for RT-PCR, blood tests, chest X-rays, and CT in cases of suggestive X-rays or negative X-rays but with highly suggestive clinical features. A structured CT report was introduced on March 13, 2020. Baseline cross sectional data of patients presenting to the ER between March 13 and 23, 2020 were used for the assessment of CT diagnostic accuracy in another study  which also included patients with negative RT-PCR.
Data including date of symptom onset, diagnosis, hospitalization, and death were retrieved from the COVID-19 Surveillance Registry, coordinated by the National Institute of Health and implemented in each Local Health Authority. Registry data were linked with the hospital radiology information system to search for CTs performed at or after the onset of COVID symptoms and with hospital discharge databases to collect information on comorbidities. Charlson index was calculated based on hospital admissions in the previous 10 years . Diabetes was ascertained through linkage with the local Diabetes Registry . The most recent lipid profile (measured in 2015-2018 and including total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and triglycerides) and blood tests at ER presentation were retrieved from the laboratory information system.
Symptoms, body temperature, and respiratory frequency at ER presentation were manually collected from medical records only for the subset of patients presenting between February 27 and March 13, 2020. Fever was defined as a body temperature >37.5°C, or, when this value was not available, self-reported fever in preceding days. Dyspnea/polypnea was defined as a respiratory frequency >18 breaths per minute or reported dyspnea in preceding ten days.
Blood tests and RT-PCR
The levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), white blood cell, lymphocyte, neutrophil, and platelet counts measured at ER presentation were collected. Oxygen saturation level (SO2) was also collected for patients who had an arterial blood gas analysis before being provided with oxygen support. The tests were carried out in the Hospital Clinical Laboratories with routine automated methods.
To diagnose SARS-CoV-2 infection, a commercial One-Step Reverse Transcription RT-PCR (GeneFinder ™ COVID -19 PLUS Real Real Amp Kit) was used and RT-PCR assay was performed on an Applied Biosystems 7500 Sequence Detection System.
CT acquisition technique
CT scans were performed using one of three scanners (128-slice Somatom Definition Edge, Siemens Healthineers; 64-slice Ingenuity, Philips Healthcare; 16-slice GE Brightspeed, GE Healthcare) without contrast media injection, with the patient in supine position, during end-inspiration. Scanning parameters were tube voltage 120 KV, automatic tube current modulation, collimation width 0.625 or 1.25 mm, acquisition slice thickness 2.5 mm, and interval 1.25 mm. Images were reconstructed with a high-resolution algorithm at slice thickness 1.0/1.25 mm.
CT structured reporting and retrospective analysis
Between March 13 and March 23, 2020, each radiologist completed a routine CT report and a structured report that included the presence/absence of ground-glass opacities and consolidations, and the extension of pulmonary lesions using a visual scoring system (< 20%, 20-39%, 40-59%, ≥ 60%) .
CTs performed between February 27 and March 13, 2020 (before the introduction of the structured report) were retrospectively reviewed by a chest radiologist with 15 years’ experience (LS) to collect the same parameters described above, including visual scoring. One hundred consecutive CTs were also reviewed by a radiologist with 3 years’ experience (GB) to assess interrater agreement.
Continuous variables were reported as median and interquartile range, and categorical variables as proportions. Single imputation procedure using truncated regression adjusted for sex, age, and comorbidities was used to deal with the problem of any missing values (Supplementary Material).
Cox proportional hazards models were used to estimate Hazard ratios (HR) with 95% confidence intervals (95% CI) for death, first by univariable model adjusted for age, sex, and calendar time (weeks since the beginning of the outbreak). Statically significant clinical, laboratory, and imaging variables were then used to develop two prognostic multivariable models, with and without CT disease extension. Sensitivity analyses were performed by stratifying the models by time since symptom onset (<8 and ≥8 days) and SO2 levels (<95% and ≥95%) and by excluding patients aged over 85 years, with CT disease extension ≥ 60%, or who had died within 48 hours from admission. The performance of the models was assessed using receiver operating characteristic (ROC) curves for 30-day death rate. On the same original sample, we fitted a logit model and used K-fold cross-validation to obtain a bias-corrected estimate of predictive accuracy. This technique averages the AUCs corresponding to each fold and applies the bootstrap procedure to the cross-validated AUC. We used 10 folds, with the exception of sensitivity analyses for ≥8 days from symptom onset and SO2 level ≥95%, in which we applied 7 and 5 folds respectively, to ensure a minimum outcome frequency in each test set. We reported cross-validated mean AUC (cvAUC), and bootstrap bias-corrected (BBC) 95%CI, with and without CT extension.
We used the kappa-statistic measure of weighted interrater agreement for a double reading of CT disease extension.
We used Stata 13.0 SE (Stata Corporation, Texas, TX) software package.