Setting
In the Reggio Emilia province (Northern Italy, 532,000 inhabitants, six hospitals), the first case of SARS-CoV-2 infection was diagnosed on February 27, 2020. Up to June 14, there were 4950 virologically-confirmed cases. The 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.
Study design and population
This was an observational cross-sectional study including all consecutive patients who presented to the Reggio Emilia province emergency rooms (ERs) between February 27 and March 23 for suspected COVID-19, underwent chest CT scan and blood tests at ER presentation and were RT-PCR positive for SARS-CoV-2 within 10 days from ER presentation.
During the COVID-19 outbreak, the diagnostic protocol for patients presenting to the ER for suspected COVID-19 included nasopharyngeal and oropharyngeal swabs for RT-PCR, blood tests and chest X-rays, and a CT scan in cases of suggestive X-ray findings or negative X-rays but highly suggestive clinical features. A structured CT report was introduced on March 13.
Data collection
Data were retrieved from the COVID-19 Surveillance Registry coordinated by the National Institute of Health and implemented in each Local Health Authority. This registry collects information about date of symptom onset, diagnosis, hospitalization and death or recovery of patients testing positive for SARS-CoV-2 RNA by RT-PCR. Information is directly collected from the patient himself/herself through daily telephone contact when cared for in an outpatient setting and from electronical medical records when hospitalized. Data from the COVID-19 Surveillance Registry were linked with the provincial Radiology Information System to search for CT scans performed at the moment of or after the onset of COVID symptoms. For all included patients, hospital discharge databases were linked to the COVID-19 Registry to identify hospital admissions in the 10 years preceding COVID-19 hospitalization in order to calculate the Charlson index for each patient [13].
Blood tests and RT-PCR
Laboratory results for C-reactive protein (CRP), lactate dehydrogenase (LDH), white blood cells, lymphocytes, neutrophils, and platelets were measured on ER admission in the entire cohort. Results of arterial blood gas analysis were also collected for patients who had them measured before receiving oxygen support. For patients presenting to ER up to March 13, results for total bilirubin, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), albumin, procalcitonin and prothrombin time (PT) were also collected. Complete blood counts were obtained with Siemens ADVIA2120i (Siemens Healthineers, Erlangen, Germany) on BD Vacutainer K2-EDTA-anticoagulated whole blood (Becton Dickinson, Franklin Lakes, NJ, US); PT was measured with Siemens Thromborel S on a Sysmex CS-5100 automated coagulometer (Sysmex Corporation, Kobe, Japan) in plasma samples obtained after centrifugation at 1500 g for 15 minutes of whole blood collected in 1.8 mL BD Vacutainer tubes with 3.2% sodium citrate 0,109 M; arterial blood gases were analyzed with ABL800 flex (Radiometer, Copenaghen, Denmark) on heparinized blood collected in BD syringes for arterial blood collection; procalcitonin concentrations were measured with LIAISON BRAHMS PCT II GEN on a LIAISON XL (DiaSorin, Saluggia VC, Italy) in plasma samples collected in lithium heparin BD Vacutainers. All other biochemical tests were measured with Siemens automated methods (wide-range CRP, AST, ALT, TBIL_2, ALB, CREA_2, LDPL) on ADVIA-1800 chemistry analyzers in lithium heparin plasma samples: immunoturibidmetric wide-range CRP, enzymatic methods for AST, ALT and LDH (forward reaction), colorimetric methods for creatinine (kinetic Jaffe reaction), bilirubin (vanadate oxidation method) and albumin (bromocresol green endpoint). Internal quality control and external quality assessment were implemented for all these measurands during the study period.
To diagnose SARS-CoV-2 infection, a commercial one-step reverse transcriptase-polymerase chain reaction (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 (Applied Biosystems, Foster City, CA, United States).
CT acquisition technique
CT scans were performed using one of three scanners (128-slice Somatom Definition Edge, Siemens Healthcare; 64-slice Ingenuity, Philips Healthcare; 16-slice GE Brightspeed, GE Medical Systems) without contrast media injection, with the patient in the 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. Patients wore face masks, and thorough decontamination of the room was performed after each patient.
CT structured reporting and retrospective analysis
In the period between March 13 and March 23, during routine CT reporting, each radiologist completed both the usual radiology report as well as a structured report, including the presence/absence of GGO and consolidations, and the extension of pulmonary lesions using a visual scoring system (< 20%, 20-39%, 40-59%, and ≥60% of parenchymal involvement) (Fig. 1) (preprint: Besutti G et al., DOI: 10.21203/rs.3.rs-26275/v1). Chest CTs which were performed in this time frame were not retrospectively reviewed.
CT scans performed in the time period between February 27 and March 13 were retrospectively reviewed by an experienced radiologist. Besides the three parameters described above (GGO, consolidations, and visual scoring), data about the presence of crazy-paving pattern, pleural effusion, and mediastinal or hilar lymph node enlargement (short axis >1 cm) were also recorded.
Statistical Analyses
Laboratory results are reported as medians (interquartile range, IQR). Distribution of CT findings across multiple qualitative and quantitative (lung extension) classes are reported; the association between qualitative CT findings, clinical and demographic variables and degree of parenchymal involvement was evaluated through Fisher’s exact test. The associations between CT findings and laboratory results were evaluated with multiple linear regression models adjusted for confounders sex and age. P values are reported as continuous measures and no preset significance threshold was used. Analyses were performed using software packages R 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria) and MedCalc 18.2.1 (MedCalc Software, Ostend, Belgium).