key: cord-0684180-wd56fx5u
authors: Schalekamp, S.; Bleeker-Rovers, C.P.; Beenen, L.F.M.; Quarles van Ufford, H.M.E.; Gietema, H.A.; Stöger, J.L.; Harris, V.; Reijers, M.H.E.; Rahamat-Langendoen, J.; Korevaar, D.A.; Smits, L.P.; Korteweg, C.; van Rees Vellinga, T.; Vermaat, M.; Stassen, P.M.; Scheper, H.; Wijnakker, R.; Borm, F.J.; Dofferhoff, A.S.M.; Prokop, W.M.
title: Chest CT in the Emergency Department for Diagnosis of COVID-19 Pneumonia: Dutch Experience
date: 2020-11-17
journal: Radiology
DOI: 10.1148/radiol.2020203465
sha: b114ceaf15f0f09bb379eafd8689bded1524f645
doc_id: 684180
cord_uid: wd56fx5u

BACKGROUND: Clinicians need rapid and reliable diagnosis of coronavirus disease 2019 (COVID-19) for proper risk stratification, isolation strategies, and treatment decisions. PURPOSE: To assess the real-life performance of radiologist emergency department chest CT interpretation for diagnosing COVID-19 during the acute phase of the pandemic, using the COVID-19 reporting and data system (CO-RADS). MATERIALS AND METHODS: This retrospective multicenter study included consecutive patients who presented to emergency departments in six medical centers between March and April 2020 with moderate to severe upper respiratory symptoms suspicious for COVID-19. As part of clinical practice, chest CT was obtained for primary workup and scored using the 5-point CO-RADS scheme for suspicion of COVID-19. CT was compared with SARS-CoV-2 RT-PCR, and a clinical reference standard established by a multidisciplinary group of clinicians based on RT-PCR, COVID-19 contact history, oxygen therapy, timing of RT-PCR testing and likely alternative diagnosis. Performance of CT was estimated using area under the receiver operating characteristics curve (AUC) analysis and diagnostic odds ratios (OR) against both reference standards. Subgroup analysis was performed based on symptom duration grouped presentations of < 48 hours, 48 hours through 7 days, and > 7 days. RESULTS: A total of 1070 patients (median age 66, IQR 54-75, 626 men) were included, of whom 536/1070 (50%) had a positive RT-PCR, 137/1070 (13%) patients were considered to have a possible or probable COVID- 19 based on the clinical reference standard. Chest CT yielded an AUC of 0.87 (95%CI 0.84-0.89) compared with RT-PCR and 0.87 (95%CI 0.85-0.89) compared with the clinical reference standard. A CO-RADS score ≥4 yielded an OR of 25.9 (95%CI 18.7-35.9) for a COVID-19 diagnosis by RT-PCR, and an OR of 30.6 (95%CI 21.1-44.4) by the clinical reference standard. For symptom duration of less than 48 hours, the AUC fell to 0.71 (95%CI 0.62-0.80; P<.001). CONCLUSION: Chest CT analysis using the COVID-19 reporting and data system (CO-RADS) enables rapid and reliable diagnosis of COVID-19, particularly when symptom duration is greater than 48 hours. See also the editorial by Elicker.

The ongoing coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought about a need for timely and high diagnostic performance tests for detecting COVID-19. The reference standard for diagnosing COVID-19 is a SARS-CoV-2 realtime reverse-transcription polymerase chain reaction (RT-PCR) in respiratory tract specimens.

Unfortunately, RT-PCR has limited sensitivity, and clinical test performance is dependent on test sample quality, viral load kinetics, and duration of symptoms (1) (2) (3) (4) (5) . Moreover, the time required for laboratory testing and reporting of RT-PCR results can be substantial, which is undesirable in crowded emergency departments. Hence, in hospitals there is a need for rapid and reliable diagnostics of COVID-19 for appropriate isolation in patient groups with high suspicion of disease. CT is widely available and offers the potential of fast triage and robust rapid diagnosis with limited burden to patients. However, the use of CT scanning for diagnosing COVID-19 has been strongly debated with mixed recommendations (6, 7) .

The Dutch Radiological Society has developed a standardized reporting scheme for chest CT in patients presenting with moderate to severe symptoms of COVID-19 (8) . This 'COVID-19 reporting and data system' (CO-RADS) is a likelihood classification for the presence of pulmonary involvement of COVID-19, with scores varying from 1 (very low suspicion) to 5 (very high suspicion), dependent on the type and distribution of the pulmonary abnormalities (Table 1) . This CT classification has moderate to substantial interobserver agreement (8) . Yet, the performance of CO-RADS and its clinical applicability have not been validated in a real-life setting.

This multicenter study aimed to assess the performance of the CO-RADS classification for diagnosing in patients presenting to the emergency department with moderate to severe symptoms suspicious for COVID-19, both for the overall study group and stratified by duration of symptoms. Chest CT was compared with two reference standards: SARS-CoV-2 RT-PCR, as well as a clinical diagnostic reference standard.

This study was approved by the institutional review boards of all participating centers. Informed consent was waived by the local IRBs prior to the study.

This retrospective, multicenter study in 4 university medical centers and 2 large teaching hospitals evaluated consecutive adult patients presenting to the emergency department between March 20th and April 3rd 2020* (April 10th for center F) with moderate to severe symptoms suspicious of COVID-19 who received a non-contrast enhanced CT-scan at presentation. Suspected COVID-19 was defined as (a) cough and clinically relevant dyspnea requiring hospital admission with or without fever >38 °C, (b) fever without a known cause or (c) fever with anosmia. As standard practice in all these hospitals, patients received a chest CT scan if there was a potential indication for hospital admission.

Patients were excluded from analysis if RT-PCR was not performed or if they were transferred from other hospitals with a known, RT-PCR proven COVID-19 diagnosis. Patients who only had a chest CT with intravenous contrast were also excluded. Patients without reported CO-RADS were excluded from further analysis. Demographic and clinical information, including duration of symptoms, was retrieved from electronic patient records.

Non-contrast enhanced CT scans were obtained with various CT scanners (Canon Aquilion Vision, Canon Aquilion One Genesis, Canon Medical Systems, Otawara Japan; Somatom Force, Somatom Definition Flash, Somatom Definition AS+, Siemens Healthineers, Erlangen, Germany; Lightspeed 16, GE Healthcare, Chicago, IL; Ingenuity 128, Philips Healthcare, Amsterdam, the Netherlands) according to existing local imaging protocols, preferably a low dose protocol (Table E1 ). All scans were prospectively evaluated by local radiologists with varying levels of experience as part of regular care, I n P r e s s without knowledge of RT-PCR results. The current study exclusively used the CO-RADS classification as adjudicated in the official radiological report.

CT was compared with two reference standards. The first reference standard was SARS-CoV-2 RT-PCR of a clinical specimen. COVID-19 infection was considered 'proven' if at least one RT-PCR for SARS-CoV-2 in a throat, nasal, sputum, bronchoalveolar lavage fluid and/or fecal sample was positive. If initial RT-PCR was negative, subsequent RT-PCR testing was generally performed, depending on the clinical likelihood of disease.

A reference standard for COVID-19 diagnosis has yet to be established. While widely used, a large proportion of patients with negative RT-PCR remain clinically highly suspect for COVID-19. In daily routine, this subgroup is isolated and remains in isolation until COVID-19 is ruled out clinically and/or by repeated RT-PCR in order to avoid nosocomial COVID-19 transmission to non-infected patients. To address the limited sensitivity of PCR and the need to avoid missing a diagnosis in patients who have COVID-19 in the inpatient setting, the study established a clinical reference standard that was designed to be highly sensitive ( Figure 1 https://www.medcalc.org; 2020). P values <.05 were considered significant.

Of 1833 total patients with suspected COVID-19, 763 were excluded from the study group. Eighty-eight patients were excluded because they were not diagnosed in an emergency department, 403 were excluded because they had no or only mild symptoms, 129 had no RT-PCR test, 53 other had already a RT-PCR proven COVID-19, 56 had no CO-RADS in the original report, and 34 had a contrast enhanced CT, leaving a total of 1070 patients were included in this study ( Figure 2 ). In the study group 626/1070 (59%) were men. Median age was 66 (IQR 54-75). Median duration of symptoms at admission was 7 days (IQR 3-10). Baseline patient characteristics for each center are shown in Table 2 . Table 3) .

Validation results CO-RADS Using RT-PCR as a reference standard, AUC was 0.87 (95%CI 0.84-0.89; range across hospitals 0.82-0.90; Table 4 ). At a CO-RADS positivity threshold of ≥4, sensitivity was 86% (95%CI 83%-89%), and specificity was 81% (95%CI 78%-84%), and the odds ratio for a COVID-19 diagnosis was 25.9 (95%CI 18.7-35.9).

Compared with the clinical reference standard, AUC was 0.87 (95%CI 0.85-0.89; range across hospitals 0.85-0.89). At a CO-RADS positivity threshold of ≥4, sensitivity was 77% (95%CI 74%-81%) and specificity was 90% (95%CI 87%-93%), and the odds ratio for a COVID-19 diagnosis was 30.6 (95%CI I n P r e s s 21.1-44.4). Results per CO-RADS category are visualized in Figure 3 , and results at different CO-RADS cut-offs are displayed in Table 5 . Previous studies have reported higher sensitivities for CT diagnosis of COVID-19 (3, 9, 10) , but this may be exaggerated due to biased samples and cohorts (11) . Reports on CT specificity are scarce and thus far disappointingly indicating values often below 50% (3, 6, (12) (13) (14) (15) (16) (17) . Previous studies did not use a well circumscribed imaging classification system (3, 10) . Our study may indicate that employing CO-RADS improves CT performance in diagnosis of COVID-19 in clinical practice. Our observation that CT had lower performance within the first 48 hours of symptoms, is in line with a recent observational study (18) . Since sensitivity of RT-PCR declines after 7 days of symptoms (1, 19) , CT may aid diagnosing COVID-19 in patients presenting with a longer duration of symptoms.

Beyond diagnostic challenges, the first wave of COVID-19 also introduced patient management issues related to workflow, isolation, personal protective equipment, and treatment decisions. During initial risk estimation in the emergency department, RT-PCR results are usually not immediately available and even when they come available, negative RT-PCR does not exclude COVID-19, especially when the pretest probability of COVID-19 is high (20) . Our study showed that CT can be a useful risk stratification tool for COVID-19: which may be advantageous in to counteract emergency department crowding (21) . Table E2 ). We recommend patients with CO-RADS 4 or 5 and a negative RT-PCR should remain isolated in a single bedroom until repeat RT-PCR is negative or an alternative diagnosis is found that explains the complaints. reporting and data systems such as BI-RADS (1.2-14%) (25) and LUNG-RADS (6%) (26) , but much lower than PI-RADS (40%) (27) .

Our study has limitations. The CO-RADS classification was introduced in the early phase of the first COVID-19 peak in the Netherlands. Radiologists may not have been optimally trained, which could have negatively influenced performance. In addition, we focused on patients presenting to the emergency department and incidence of COVID-19 was high. Our findings may not be reproducible to lower-incidence settings. Our clinical reference standard was designed to be highly sensitive but was not validated in a control group and may be false positive, especially in the 'possible' COVID-19 category. Furthermore, before implementation of this CT strategy, good infection control processes need to be in place. Specifically, cleaning the CT scanner room and safe room turnover for the safe scanning of new patients must be considered.

The implications of our results are of potential importance. Chest CT exams interpreted using the CO-RADS system allow for a rapid test result in the emergency department of patient with suspected COVID-19 pneumonia. This suggests a potential role for chest CT in helping to optimize risk stratification and isolation strategies of patients urgently presenting for hospital care during the first and second wave of this pandemic.

In conclusion, using the CO-RADS chest CT reporting system for emergency department subjects, pulmonary manifestations of COVID-19 were detected in more than 95% of patients with moderate to severe upper respiratory symptoms 48 hours after symptom onset. CO-RADS score greater than or equal to 4 provided odds ratios above 25 for the diagnosis of COVID-19. I n P r e s s 

Division of Infectious Diseases, and Radboud Center for Infectious Diseases

Location AMC, Department of Radiology

Amsterdam Institute for Global Health and Development, Department of Global Health

Department of Infectious Diseases

SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

Detection of 2019 novel coronavirus (2019-nCoV) by realtime RT-PCR

Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

Detection of SARS-CoV-2 in Different Types of Clinical Specimens

Stability issues of RT-PCR testing of SARS-CoV-2 for hospitalized patients clinically diagnosed with COVID-19

Radiological Society of North America Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA

The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society

CO-RADS -A categorical CT assessment scheme for patients with suspected COVID-19: definition and evaluation

Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR

Clinical Characteristics of Coronavirus Disease 2019 in China

Diagnostic Tools for Coronavirus Disease (COVID-19): Comparing CT and RT-PCR Viral Nucleic Acid Testing

Diagnostic Performance of CT and Reverse Transcriptase-Polymerase Chain Reaction for Coronavirus Disease 2019: A Meta-Analysis

A role for CT in COVID-19? What data really tell us so far

Clinical Features and Chest CT Manifestations of Coronavirus Disease

Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei

Diagnostic performance of chest CT to differentiate COVID-19 pneumonia in non-high-epidemic area in Japan

Chest CT Features of COVID-19 in

Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection

Real-time RT-PCR in COVID-19 detection: issues affecting the results

False Negative Tests for SARS-CoV-2 Infection -Challenges and Implications

Emergency imaging after a mass casualty incident: role of the radiology department during training for and activation of a disaster management plan

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study

Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms

Use of BI-RADS 3-probably benign category in the American College of Radiology Imaging Network Digital Mammographic Imaging Screening Trial

Performance of Lung-RADS in the National Lung Screening Trial: a retrospective assessment

Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study

I n P r e s s Abbreviations: COVID-19 = coronavirus disease 2019; CO-RADS = COVID-19 reporting and data system; RT-PCR = real-time reverse-transcription polymerase chain reaction. Non-pulmonary infection 2Pulmonary embolism 1

This table shows the number of specific alternative diagnosis (21/40 (53%) that were established in the 'no' COVID-19 patients with a chest CT score CO-RADS of 4 and 5.