{'fraction_non_alphanumeric': 0.03240097289784573, 'fraction_numerical': 0.018328700486448923, 'mean_word_length': 5.046743697478991, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Variable computed tomography appearances of COVID-19

The coronavirus disease 2019 (COVID-19) is typically diagnosed by specific assays that detect viral nucleic acid from the upper respiratory tract; however, this may miss infections involving only the lower airways. Computed tomography (CT) has been described as a diagnostic modality in the COVID-19 diagnosis and treatment plan. We present a case series with virologically confirmed COVID-19 pneumonia. Variable CT features were observed: consolidation with ground-glass opacities, ground-glass opacities with subpleural reticular bands, and an anterior-posterior gradient of lung abnormalities resembling that of acute respiratory distress syndrome. In one patient, we noted evolution of CT findings, where there was interval resolution of bilateral lung consolidation with development of bronchiolectasis and subpleural fibrotic bands. While sensitive for detecting lung parenchymal abnormalities in COVID-19 pneumonia, CT for initial diagnosis is discouraged and should be reserved for specific clinical indications. Interpretation of chest CT findings should be correlated with duration of symptoms to better determine the disease stage and aid in patient management.


INTRODUCTION
Reports in December 2019 from Wuhan, Hubei Province, China of a cluster of patients with severe pneumonias heralded a pandemic which has affected most of the world. As of 31 March 2020, 750,890 confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases and 36,405 deaths have been reported globally. (1) While extraordinary measures have been taken by many governments in an effort to slow the spread of this virus, over the longterm, control of this outbreak will rely on accurate diagnosis and isolation of infected individuals.
Typically, diagnosis of the novel coronavirus disease 2019 (COVID-19) relies on polymerase chain reaction (PCR) of respiratory specimens to detect SARS-CoV-2 nucleic acid. This test is highly specific, but swabs of the upper respiratory tract may lack sensitivity when the infection is confined to the lower airways. Chest computed tomography (CT) has been shown to have a high sensitivity in the Chinese population. (2) The use of chest CT in the diagnosis of COVID-19 was described in February 2020, in the diagnosis and treatment plan for COVID-19 pneumonia, issued by the National Health Commission of the People's Republic of China. (3) We present a case series of three patients with confirmed COVID-19 pneumonia in our institution, followed by a discussion of the role of chest CT for this novel respiratory tract infection. Informed consent from the patients in this study was waived by the Singapore Ministry of Health, under the Infectious Diseases Act (Chapter 137).

Case 1
A 52-year-old woman with a background of hypertension presented with cough, shortness of breath and fever for four days. There was no recent travel or contact history. She was admitted for isolation and further management. She was haemodynamically stable and physical examination was unremarkable. Laboratory results revealed mildly elevated C-reactive protein (CRP) of 7.1 mg/L (0.0-5.0 mg/L), while neutrophil level was mildly reduced at 1.43 × 10 9 /L (1.9-6.60 × 10 9 /L). Nasopharyngeal reverse-transcription-polymerase chain reaction (RT-PCR) tested positive for SARS-CoV-2. Initial chest radiograph revealed right lower zone consolidation and a faint ground-glass opacity in the right upper zone (Fig. 1). During the admission, a CT study of the abdomen and pelvis was performed for evaluation of left flank pain, which revealed left renal calculi. Limited sections of the lung bases demonstrated consolidation with surrounding ground-glass opacities in the right lower lobe (Fig. 1). Focal consolidation, seen in the lingula, was not evident on chest radiograph. This illustrates the sensitivity of CT in detecting ground-glass opacities. She remained stable during admission without requiring oxygen supplementation and was discharged well after 11 days.

Case 2
A 56-year-old man from Shandong, China presented with fever and cough for a week, as well as watery diarrhoea for two days. He had a significant medical history of well-controlled concern of biliary obstruction. A CT study of the abdomen and pelvis was negative for biliary obstruction. The limited sections of the lung bases demonstrated subpleural reticular bands and ground-glass opacities with perilobular opacities (Fig. 2). The patient remained stable during admission without requiring oxygen supplementation and was discharged well after 12 days.

Case 3
A 71-year-old man with a history of poorly controlled Type 2 diabetes mellitus presented with fever and lethargy for a week. He had no recent travel or contact history. He was febrile at presentation with a temperature of 38.7°C but maintained oxygen saturation of 95% on room air. Auscultation of the lungs revealed coarse crepitations in the right mid-to lower zones and left lower zone. Laboratory results revealed mildly elevated CRP of 138.2 mg/L (0.0-5.0 mg/L), mildly reduced total white blood cell count of 3.5 × 10 9 /L (4.0-9.6 × 10 9 /L) and lymphocyte count of 0.48 × 10 9 (1.1-3.1 × 10 9 ). Nasopharyngeal RT-PCR was positive for SARS-CoV-2. During admission, he had increasing oxygen supplementation requirement, prompting admission to the intensive care unit (ICU), where he was intubated and received mechanical ventilation. A CT pulmonary angiogram was performed to exclude pulmonary embolism as a cause of desaturation. There was multifocal bilateral lung consolidation with diffuse involvement of the lower lobes (Fig. 3). An anterior-posterior gradient of abnormalities was observed with consolidation affecting the posterior aspects of bilateral lungs, while diffuse ground-glass opacities were noted in the non-dependent areas of the bilateral upper lobes and middle lobe (Fig. 4). Repeat CT pulmonary angiogram, performed eight days later, showed regression of ground-glass opacities, which were replaced by organising consolidation and reticular changes (Fig. 5). Bronchiolar dilatation was notable in the lower lobes and bilateral pleural effusions had grown larger. Both studies were negative for pulmonary embolism.
Unfortunately, during the admission, he developed right upper limb deep venous thrombosis secondary to prior central venous catheter insertion. This was further complicated by acute lower gastrointestinal bleed secondary to the use of anticoagulants. A CT mesenteric angiogram was performed to identify the site of bleeding, which was negative. The limited sections of the lung base showed improvement of bilateral lower lobe consolidation with development of subpleural reticular opacities and traction bronchiectasis related to fibrosis (Fig. 6). The patient remains warded at the time of writing.

DISCUSSION
A diverse pattern of CT findings in COVID-19 pneumonia has been reported, with groundglass opacities and mixed ground-glass opacities with consolidation being more commonly seen, while other features such as crazy-paving pattern, reverse halo sign, subpleural bands and bronchiectasis have also been described. (4)(5)(6)(7)(8) Multifocal bilateral lung involvement, predominantly in the lower lobes and peripheral distribution, was the most common pattern of distribution seen in COVID-19 pneumonia. (4)(5)(6)(7)(8) This pattern of multifocal bilateral lower lobe involvement was seen in all three cases in our series. Studies on the evolution of CT findings along the course of the disease showed progression of ground-glass opacities with bilateral lung involvement during the first week of symptoms, which worsens into dense consolidation in the second week. (9,10) Following the second week, as the disease improves, there would be resolution of lung consolidation and development of a reticular pattern, septal thickening and bronchiolectasis, suggestive of fibrosis. (9,10) Patchy ground-glass opacities with subpleural bands in bilateral lower lobes, as seen in Case 2 (Fig. 2), likely represents partial convalescence of lung consolidation with early fibrosis. In addition, perilobular opacities were appreciated in this case, a sign described in organising pneumonia. (11) The evolution of lung changes is best illustrated in Case 3, where dense bilateral lung consolidation showed interval resolution and subsequent formation of subpleural reticular opacities and bands with traction bronchiolectasis, indicative of fibrosis. Two recent studies described peak lung involvement about 6-11 days from symptom onset. (12) Diffuse lung consolidation, architectural distortion, traction bronchiectasis and pleural effusions have been reported to be more commonly found in severe and fatal disease. CT has been shown to be more sensitive compared to a chest radiograph, being able to detect ground-glass opacities, which are not discernible on a radiograph. (16) In addition, CT provides valuable information on the degree of severity of pneumonia, which aids in the prognostication of the patient. (5) In spite of these advantages, factors such as increased cost, higher radiation dose and the need for longer breath holds for accurate CT image acquisition compared to chest radiographs should also be considered. Furthermore, strict infection control related to the transfer of patients from the isolation room to the radiology department for a CT study and subsequent decontamination of the CT room following a study needs to be in place.
Several studies have shown that chest CT carries a high sensitivity for the detection of COVID-19 pneumonia. (2,17,18) In a review of 51 patients with COVID-19 pneumonia, the diagnosis of viral pneumonia could be made with chest CT three days prior to positive nucleic acid test results. (18) In addition, nucleic acid test has a limited detection rate for SARS-CoV-2, giving rise to false-negative results, and often requires repeated samples. (2,17) In a large retrospective study of 1,014 patients in Wuhan, China, chest CT carried a true-positive rate of 88% compared to 59% with RT-PCR. (2) In the face of a shortage of PCR test kits and the urgent need for diagnosis despite negative PCR, clinical diagnosis was made based on typical chest CT findings during the peak of the outbreak in Hubei Province, China. (2) This approach may be justifiable in an epidemic area where there is high pre-test probability for the disease, compounded by the limited availability of test kits and laboratory support during the outbreak.
However, in our opinion, these results may not be extrapolated to less affected areas with a lower pre-test probability for COVID-19 pneumonia.
In fact, recent recommendations by the American College of Radiology and the British Society of Thoracic Imaging discourage the use of CT as the first-line diagnostic test to diagnose COVID-19, given its untested specificity. (19,20) In our institution, CT is reserved for severe cases where other causes for desaturation such pulmonary embolism are suspected, or when there is discordance between the clinical and chest radiographic findings. This explains why the CT appearances of pulmonary involvement for our first two cases were derived from abdominal CT.
In conclusion, this case series of three COVID-19 pneumonia patients highlights the variable chest CT features during the acute and convalescent phases. Chest CT is a highly sensitive tool for the delineation of the extent of lung disease, but its use as a first-line