key: cord-0913256-r7cmcqs9 authors: Turcato, G.; Zaboli, A.; Panebianco, L.; Scheurer, C.; Venturini, A.; Tezza, G.; Canelles, M. F.; Ausserhofer, D.; Pfeifer, N.; Wieser, A. title: Clinical application of the COVID-19 Reporting and Data System (CO-RADS) in patients with suspected SARS-CoV-2 infection: observational study in an emergency department date: 2020-10-27 journal: Clin Radiol DOI: 10.1016/j.crad.2020.10.007 sha: 2023cefc84fbf9e807a9888b32e0281c75449f4f doc_id: 913256 cord_uid: r7cmcqs9 • CO-RADS improves the risk classification by 65.8% in patients affected by COVID-19. • CO-RADS combined with RT-PCR presents an AUC of 0.98 for patients with COVID-19. • CO-RADS improves the risk classification by 82.1% in patients not affected by COVID-19. Early detection of patients with SARS-CoV-2 in the emergency department (ED) is essential to limit the spread of the virus and prevent its transmission within hospitals [1] . At present, the reverse-transcription polymerase chain reaction (RT-PCR) test remains the standard for the diagnosis of SARS-CoV-2 infection [2] ; however, the The data from 120 consecutive chest CT examinations in the initial ED assessment for suspected SARS-CoV-2 infection were included retrospectively. Since 25 March 2020, according to the management protocol, on arrival at the ED, patients suspected to have COVID-19 have undergone chest CT with the application of CO-RADS, as described by Prokop et al. [9] . Patient demographic, medical history, and clinical characteristics were also recorded upon arrival at the ED. In the CT imaging report, the radiologist provides the CO-RADS score, in addition to describing the thoracic imaging, making it directly available to the ED physician (Table 1) . A CO-RADS score of 1 was assigned to patients with a normal CT examination, indicating a non-infectious clinical condition; CO-RADS 2 was assigned to patients with CT examination indicating possible infectious disease, with bronchial involvement but without ground-glass opacity (GGO), where the suspicion of COVID-19 was low; CO-RADS 3 was assigned to patients an infectious image, but unsure for COVID-19, where central consolidations and small GGOs may be present, but more suggestive of other infectious or viral diseases; CO-RADS 4 was assigned based on a high, but not complete, level of suspicion, unilateral GGO, multifocal consolidations, but with predominant peribronchovascular involvement; CO-RADS 5 was assigned based on a very high level of suspicion for pulmonary involvement by COVID-19, with multifocal GGO areas, consolidations in lung regions close to visceral-pleural surfaces (including fissures), and a multi-focal, bilateral distribution (Table 1) . Both The CO-RADS score was compared primarily with the result of the reference standard RT-PCR test for SARS-CoV-2. Secondly, the discriminative ability of CO-RADS was also evaluated for the final clinical diagnosis of COVID-19. This secondary clinical outcome was obtained by adding patients with a positive RT-PCR test for SARS-CoV-2 to the patients with one or more negative RT-PCR results, but a final clinical diagnosis of COVID-19 according to hospital medical records [9] . A definite diagnosis of COVID-19 was established according to the case definition of the interim guidance issued by the World Health Organization (WHO) [2] . The study was conducted in accordance with the Local Ethics Committee (Azienda Sanitaria dell´Alto Adige, Parere nr. 57-2020) and was conducted according to the Involving Human Subjects. The categorical variables were presented as a percentage and number of events out of the total. Univariate comparisons were performed with Fisher's exact test. The continuous variables were presented as median and interquartile range. The discrimination ability of CO-RADS for at least one positive SARS-CoV-2 RT-PCR test and, subsequently, for the clinical final diagnosis of COVID-19 was evaluated using a ROC curve and the AUC. The performance of each CO-RADS score was evaluated for sensitivity, specificity, negative predictive value, positive likelihood ratio (LR+), and negative likelihood ratio (LR-). Moreover, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and the incremental J o u r n a l P r e -p r o o f AUC score (IAUC) were used to compare the predictive capacity of RT-PCR alone with the addition of the CO-RADS score to RT-PCR itself. All testing was two-tailed, with 0.05 as the level of statistical significance. Statistical analyses were performed using STATA 13.0 software (StataCorp, College Station, TX, USA). The median age of the patients was 68 years (range 60-78 years) and 60.8% (73/120) were male. Fifty-one of the 120 patients (42.5%) had moderate or severe symptoms on ED admission (respiratory rate >22 and/or saturation ≤93%). The median value of the CO-RADS score was 2 (range 1-5). The distribution of the CO-RADS score was 44.2% CO-RADS 1 (very low level of suspicion), 10% CO-RADS 2 or 3 (low level of suspicion, equivocal findings) and 45.8% CO-RADS 4 or 5 (high level of suspicion, very high level of suspicion). The characteristics of patients consecutively assessed for suspected SARS-CoV-2 infection, grouped by CO-RADS score, are listed in Table 2 . The clinical parameters of patients with higher CO-RADS scores were more altered, but there were no differences in comorbidities between the two groups. (Table 3 ). The overall discriminatory ability for COVID-19 infection is improved significantly by the application of CO-RADS, with an IAUC increase of 14.8% (p<0.001). The challenging containment of the COVID-19 pandemic in the last few months in Italy has reinforced the idea that the key to control COVID-19 is early discovery and early isolation [10] . The careful application of these rules in the ED has limited the spread of the virus within the hospital and prevented its transmission among hospitalised patients [1, 10, 11] . The lack of rapid and accurate diagnostic testing has forced EDs to perform major structural and organisational adjustments in order to isolate suspected patients and safely identify those infected; however, this has led to patients suspected of having SARS-CoV-2 infection staying in the ED for longer durations, a high risk of infection for healthcare professionals, and an exponential increase in workload [12, 13] . One problematic aspect of this tool remains the decision to perform CT on patients with mild respiratory symptoms. There is currently no unanimous consensus around this choice, but several studies report the utility of CT in recognising SARS-CoV-2infected patients [17, 18] . Although minimal compared to patients who are more symptomatic, patients with mild symptoms may present underlying COVID-19 pneumonia masked by a pulmonary functional reserve that may deteriorate over hours or days [19, 20] Although negative CO-RADS cannot exclude the presence of an infection, the system appears safer in patients with respiratory symptoms (even minor ones) than in asymptomatic patients. Therefore, the use of CO-RADS in settings other than an ED, or in patients with flu-like symptoms but without respiratory involvement, would not be recommended. Several RT-PCR tests can be repeated safely in these nonsevere patients, who do not need urgent treatment or investigations, or they can be instructed to quarantine at home. CO-RADS 5 for the clinical diagnosis of COVID-19 correlated less well with RT-PCR than CO-RADS 4. Although a COVID-19-specific radiological pattern has been defined, some conditions can be misdiagnosed. In particular, cases of other viral interstitial pneumonias, aspiration pneumonia, and organising pneumonia with congestive heart failure can be observed as peripheral GGOs, vascular thickening, and subpleural bands, mimicking SARS-CoV2 infection. The need for rapid diagnosis in an emergency setting together with the appearance of a new pathological entity and lack of specific radiological signs could explain the gap between CO-RADS 4 and 5. Other possible limitations should be reported. The first is bias due to the retrospective nature of the study; however, bias was minimised because all patient information obtained in the ED was recorded precisely during the pandemic period. The second is that the CO-RADS score assigned in the ED may have influenced the final medical J o u r n a l P r e -p r o o f diagnosis and thus improved the performance of the tool. Third, conducting the study during a phase of the pandemic characterised by a high incidence of patients with COVID-19-like symptoms, and by a high prevalence of COVID-19 infections, may have increased CO-RADS performance. Therefore, despite good preliminary evidence, prospective studies will be required in the coming months (when the incidence of other diseases will probably increase), to confirm the possible role of CO-RADS in clinical practice. Patient with positive RT-PC positive CO-RADS score (4 or There are no CO-RADS 0 and 6 in the present study. The CO-RADS score was immediately available for the patient's evaluation in ED, obviously not with reversetranscription polymerase chain reaction (RT-PCR) results (usually available 24 h later) and therefore CO-RADS 6 was not present. 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