key: cord-0921943-497z31h6
authors: Bernheim, Adam; Mei, Xueyan; Huang, Mingqian; Yang, Yang; Fayad, Zahi A.; Zhang, Ning; Diao, Kaiyue; Lin, Bin; Zhu, Xiqi; Li, Kunwei; Li, Shaolin; Shan, Hong; Jacobi, Adam; Chung, Michael
title: Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection
date: 2020-02-20
journal: Radiology
DOI: 10.1148/radiol.2020200463
sha: e7f5a29c5a8b04b195313b6ff79294bbb3fbb452
doc_id: 921943
cord_uid: 497z31h6

In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, “crazy-paving” pattern and the “reverse halo” sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).

Wuhan, the capital of central China's Hubei province [1, 2] . While the virus likely has a zoonotic origin related to the city's Huanan Seafood Market, widespread human-to-human transmission has resulted in 73,451 cases in 26 countries with 1,875 deaths as of February 18, 2020 [3 -7] . Disease was first reported in the United States on January 20, 2020, and the total number of cases in the United States has reached 15 as of February 17, 2020 [7, 8] . The most common presenting clinical symptoms are fever and cough in addition to other non-specific symptomatology including dyspnea, headache, muscle soreness, and fatigue [9] . About 20% of cases are severe, and mortality is approximately 3% [10] . The World Health Organization (WHO) declared a global health emergency on January 30, 2020 [11] . This is the seventh known coronavirus to infect humans [1] . As clinical physicians, epidemiologists, virologists, phylogeneticists, and others work with public health officials and policymakers to understand infection pathogenesis and control disease spread, some early investigators have observed imaging patterns on chest radiography and computed tomography (CT) [14 -25] . For instance, an initial prospective analysis in Wuhan revealed bilateral lung opacities on 40 of 41 (98%) chest CTs in infected patients and described lobular and subsegmental areas of consolidation as the most typical findings [4] . Other investigators examined chest CTs in 21 infected patients and found high rates of ground-glass opacities and consolidation, sometimes with a rounded morphology and peripheral lung distribution [26] . Another group evaluated lung abnormalities related to disease time course and found that chest CT showed the most extensive disease approximately ten days after symptom onset. [16] . Thoracic radiology evaluation is often key to the evaluation of patients suspected of COVID-19 infection. Prompt recognition of disease is invaluable to ensure timely treatment, and from a public health perspective, rapid patient isolation is crucial for containment of this communicable disease.

In this study, we characterize chest CT findings in 121 patients infected with COVID-19 in China in relationship to the time between symptom onset and the initial CT scan. This study builds on initial work by early investigators during the first few weeks of the outbreak by evaluating a larger number of patients as well as by examining imaging features as the disease moves into the more subacute phase and/or earlier detection with increased vigilance for detection. We hypothesized that certain CT findings may be more common depending on the time course of infection.

Our institutional review board (IRB) waived written informed consent for this retrospective study that evaluated de-identified data and involved no potential risk to patients. To avert any potential breach of confidentiality, no link between the patients and the researchers was made available.

From January 18, 2020, until February 2, 2020, 121 adult patients admitted to four hospitals in four provinces in China with confirmed COVID-19 and who underwent chest CT were enrolled in our study. Twenty-one of these patients were previously evaluated on our prior study focusing on the CT imaging manifestations of COVID-19, but were reevaluated for the purposes of this I n p r e s s new study [26] . Patient selection was consecutive in each of the four institutions, and the solitary exclusion criteria was patient age < 18 years (Table 1 ). In addition to age and gender, clinical information collected included travel and exposure history (when known). All patients were positive for COVID-19 via laboratory testing with real-time reverse transcriptase polymerase chain reaction (rRT-PCR) of respiratory secretions obtained by bronchoalveolar lavage, endotracheal aspirate, nasopharyngeal swab, or oropharyngeal swab. In addition, the number of rRT-PCR tests performed on each patient was tabulated (when known), on which test a positive result was found was tabulated, and the number of days between symptomology onset and date of first positive test was tracked. The rRT-PCR test kits used on the patients in Twenty-two patients were from Nanchang (Jiangxi Province) and were imaged with 8-mm slice thickness CT on a Siemens Emotion 16 scanner (Siemens Healthineers; Erlangen, Germany). Sixty-nine patients were from Zhuhai (Guangdong Province) and were imaged with 1-mm slice thickness CT on a UCT 760 scanner (United Imaging; Shanghai, China). Twentytwo patients were from Chengdu (Sichuan province) and were imaged with 1-mm slice thickness CT on a Revolution scanner (GE Medical Systems; Milwaukee, WI). Eight patients were from Guilin (Guangxi province) and were imaged with 1-mm slice thickness CT on a Philips Brilliance Big Bore scanner (Philips; Amsterdam, Netherlands). All scans were performed without intravenous contrast with the patient in the supine position during endinspiration. Only the initial chest CTs were evaluated; if a patient had a follow-up CT during the study time window, it was not analyzed for this study. For each patient, the chest CT scan was evaluated for the following characteristics: (1) presence of ground-glass opacities, (2) presence of consolidation, (3) laterality of ground-glass opacities and consolidation, (4) number of lobes affected where either ground-glass or consolidative opacities were present, (5) degree of involvement of each lung lobe in addition to overall extent of lung involvement measured by means of a "total severity score" as detailed I n p r e s s below, (6) presence of nodules, (7) presence of a pleural effusion, (8) presence of thoracic lymphadenopathy (defined as lymph node size of ≥10 mm in short-axis dimension), (9) airways abnormalities (including airway wall thickening, bronchiectasis, and endoluminal secretions), (10) axial distribution of disease (categorized as no axial distribution of disease, central "peribronchovascular" predominant disease, or peripheral predominant disease), and (11) presence of underlying lung disease such as emphysema or fibrosis. Other abnormalities, including linear opacities, opacities with a rounded morphology, opacities with a "reverse halo" sign, opacities with a "crazy-paving" pattern, and opacities with intralesional cavitation, were noted. Ground-glass opacification was defined as hazy increased lung attenuation with preservation of bronchial and vascular margins, whereas consolidation was defined as opacification with obscuration of margins of vessels and airway walls [27] . Each of the five lung lobes was assessed for degree of involvement and classified as none (0%), minimal (1 -25%), mild (26 -50%), moderate (51 -75%), or severe (76 -100%). No involvement corresponded to a lobe score of 0, minimal to a lobe score of 1, mild to a lobe score of 2, moderate to a lobe score of 3, and severe to a lobe score of 4. An overall lung "total severity score" was reached by summing the five lobe scores (range of possible scores, 0 -20).

The amount of time between the initial appearance of patient symptoms (such as fever, cough, etc.) and the date of both the first positive rRT-PCR test as well as the date of the initial chest CT examination was noted for each patient. Twenty seven patients were excluded because the date of first symptom appearance was unknown, leaving 94 patients for analysis. If the time interval between first clinical symptom and CT was two days or less (36 of 94 patients), the patient was considered to have been imaged in the "early" phase of illness. If the time interval was between three and five days (33 of 94 patients), the patient was considered to have been imaged in the "intermediate" phase of illness. If the time interval was between six and 12 days (25 of 94 patients), the patient was considered to have been imaged in the "late" phase of illness.

There were 61 men and 60 women studied with mean age 45.3 years (age range 18 -80 years with standard deviation 16 years).

Of the 121 patients, 27 (22%) had no ground-glass opacities and no consolidation on chest CT ( The mean total severity score was 1 (standard deviation (SD) = 1) for early patients, 4 (SD=2), for intermediate patients and 6 (SD= 4) for late patients.

Linear opacities, a "crazy-paving" pattern, and a "reverse halo" sign were all absent in the early group, but were present in the late group 20%, 20%, and 4% of the time, respectively ( Figure   5 ). In terms of distribution of disease in the axial plane, peripheral distribution was found in 8 of had an initially negative rRT-PCR result, suggesting that rRT-PCR is positive even in patients with normal chest CT. Chest CT therefore has limited sensitivity and negative predictive value early after symptom onset, and is thereby unlikely a reliable standalone tool to rule out COVID-19 infection.

Other findings of this work largely concur with early radiology investigative efforts [16] insofar as this pattern of ground-glass and consolidative pulmonary opacities, often with a bilateral and peripheral lung distribution, is emerging as the chest CT hallmark of COVID-19 infection. This pattern of disease, somewhat similar to that described in earlier coronavirus outbreaks such as SARS and MERS, also dovetails with the blueprint thoracic radiologists recognize as the archetypal response to acute lung injury whereby an initial (often infectious or inflammatory) acute insult causes ground-glass opacities that may coalesce into dense consolidative lesions, and then progressively evolve and organize in often a more linear fashion with predilection for the lung periphery (and somewhat with a "crazy" paving pattern or emergence of a "reverse halo" sign). The findings in this study, which highlight the increased frequency of such findings I n p r e s s as consolidation, bilateral disease, greater total lung involvement, linear opacities, a "crazypaving" pattern, appearance of the "reverse halo" sign, and peripheral lung distribution in patients imaged with CT a longer time after symptomatology starts, represent the CT correlate for the underlying pathophysiology of the disease process as it organizes. Moreover, the notable absence of ancillary chest CT findings such as lymphadenopathy, pleural effusions, pulmonary nodules, and lung cavitation likewise are consistent with early case descriptions.

There are several limitations to our study. Firstly, some patients were unable to be included in 

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