Study design and setting
This was a single-center cohort study aiming to evaluate outpatients with suspected COVID-19 who received medical examination at Yokohama City University Hospital, prospectively registered between 9 February, 2020 and 5 May, 2020.
Ethical approval
The Institutional Review Board at Yokohama City University Hospital approved this study (approval number B200200047). Consent for participation in this study was obtained from all patients after explaining the clinical study by verbal or a description of how to opt out. (https://www.yokohama-cu.ac.jp/amedrc/ethics/ethical/fuzoku_optout.html).
Participants
Among all patients who visited our outpatient clinic, those who exhibited COVID-19-like symptoms such as fever (over 37.5℃), fatigue, respiratory symptoms, headache, and taste or olfactory disorders, were identified and instructed to visit our separate clinic as outpatients with suspected COVID-19.
We analyzed the following baseline patient characteristics: age, sex, history of overseas travel, contact history with a confirmed COVID-19 case, and underlying comorbidities (chronic pulmonary disease, diabetes, hypertension, chronic renal failure, cardiovascular disease, cerebrovascular disease, and malignancy). We also evaluated patients’ existing symptoms such as fever, fatigue, respiratory symptoms, headache, and taste or olfactory disorders.
Interventions and measurements
CT-first triage protocol
First, patients complaining of fever, fatigue, respiratory symptoms, headache, and taste or olfactory disorder were redirected to the separate suspected COVID-19 outpatient clinic of the emergency room described above. From that time, patients were isolated from other patients and treated as if they had COVID-19. Second, a nurse in the outpatient clinic equipped with PPE briefly checked patients’ vital signs and their present histories. Then, chest CT was conducted. Our hospital was equipped with three CT scanning suites. We set one of these as a dedicated suite for patients with suspected or confirmed COVID-19. Patients with suspected COVID-19 were separated from other patients in the transport corridors and elevators to the CT suite. An 80-row CT scanner (Aquilion Prime, Canon Medical Systems, Otawara, Tochigi, Japan) was used in this study. The tube voltage setting was 120 kVp and automatic exposure control was applied. The average CT dose index volume (CTDIvol) was 9.4 ± 4.1 mGy. These settings were not specialized for CT screening of COVID-19 pneumonia, and a reduction in radiation exposure was not applied. Patients were scanned during full inspiratory breath hold; however, some patients with severe dyspnea were scanned without performing a breath hold. Two-pattern CT images were reconstructed with a slice thickness/increment of 5.0mm/5.0mm and 0.5 mm/0.5 mm. Coronal and sagittal multiplanar reconstruction images were also acquired. All CT scans were immediately interpreted by trained radiologists. During regular business hours, all CT scans were interpreted and full reports were created by board-certified radiologists from the Japan Radiological Society (10 radiologists with 6–26 years’ experience in chest radiology). Scans were also immediately checked, and necessary information on the possibility of COVID-19 pneumonia was reported to COVID-19 doctors after hours by the 10 board-certified radiologists and 9 fellows from the Department of Radiology. If necessary, fellows contacted board-certified radiologists for their opinions. CT findings were classified into five categories according to the COVID-19 Reporting and Data System (CO-RADS).21 The CO-RADS was used to assess suspected pulmonary involvement in COVID-19 on a scale from 1 (very low) to 5 (very high), as follows: CO-RADS 1, normal CT or non-infectious etiology (e.g., lung tumor, lung fibrosis); CO-RADS 2, infectious etiology that is not compatible with COVID-19 (e.g., infectious bronchiolitis, bronchopneumonia, lobar pneumonia); CO-RADS 3, equivocal findings for COVID-19 (e.g., homogeneous extensive GGO); CO-RADS 4, typical CT findings of COVID-19 (similar to CO-RADS 5) but showing some overlap with other pneumonia; CO-RADS 5, typical CT findings of COVID-19 (e.g., multifocal GGO with or without consolidation in lung regions close to visceral pleural surfaces). Representative images in each category are shown in Figure 1. Finally, patients were allocated to a “COVID-19 suspected” group or a “COVID-19 less likely” group. Patients with a suspicious clinical history (contact with an infected person and overseas travel history), suspicious findings on chest CT scan (CO-RADS 3 to 5), or who were suspected of having COVID-19 according to their clinical symptoms that were difficult to explain by the underlying disease were included in the COVID-19 suspected group. Patients with neither a suspicious clinical history nor chest CT features suggestive of COVID-19 (CO-RADS 1 to 2) were included in the COVID-19 less likely group. If patients were diagnosed as less likely to have COVID-19, isolation and PPE support were discontinued, and detailed physical and laboratory examinations were performed. However, if patients were diagnosed with COVID-19 suspected, isolation and PPE support were continued until a negative PCR test result was obtained for the patient. A PCR test for SARS-CoV-2 was performed only in COVID-19 suspected group patients. All samples obtained after 11:00 on the previous day were immediately submitted for PCR testing each day, and the results were obtained at 15:00 on the same day.
Outcomes
The primary outcome was the efficacy of the CT-first triage protocol in outpatients with suspected COVID-19. We assessed all results of PCR for SARS-CoV-2 and the final diagnoses of patients. Patients who did not undergo PCR testing were followed for up to 14 days until confirmed clinically negative for COVID-19. Secondary outcomes were the duration of isolation among all patients and safety of the medical staff and hospitalized patients. Isolation duration was defined as the time that PPE was required or that patients were isolated from medical staff and other patients to prevent COVID-19 infection. For the COVID-19 suspected group, the time to a PCR-confirmed negative result was applicable for determining the duration of isolation. The isolation duration of PCR-positive patients was excluded from the results for isolation duration in the COVID-19 suspected group because COVID-19-positive patients remained in isolation until their treatment was finished. However, in the COVID-19 less likely group, the time to a CT-confirmed negative result was applicable to determine the isolation duration. The patient data were retrospectively examined using medical records.
Statistical analysis
To account for biases, we performed the analysis after the study period was complete. Results are presented as mean ± standard deviation for quantitative data and as frequency (percentage) for categorical data. The Student’s t-test was used for continuous data. A P value <.05 was considered statistically significant. All statistical analyses were performed using Prism 7.9 J for Windows (GraphPad Software, Inc., San Diego, CA, USA).