Imaging findings in coronavirus infections: SARS-CoV, MERS-CoV, and SARS-CoV-2

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.

The authors Tomas Franquet and Yeon Joo Jeong contributed equally to the work.

introDuction
In late December 2019, the 2019 novel coronavirus pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, China, and has spread quickly worldwide. During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by the SARS-CoV, the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2 (the respiratory disease caused by SARS-CoV-2 is now called coronavirus disease-19, . Coronaviruses are enveloped viruses with a positive-sense single-stranded RNA genome and have club-shaped surface-spike glycoprotein which plays an important role in binding to receptors on host cells. After the virus enters the cells, its antigen is presented to dendritic cell or macrophage, which stimulates the body's humoral and cellular immunity ( Figure 1). Coronavirus induces lung injury by involving angiotensin converting enzyme, by cell apoptosis induced by specific viral proteins, and by cytokine storm, the uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokine and chemokines 1 (Figure 1).
It has been reported that CT patterns of pulmonary viral infection are related to their pathogenesis and most viral pneumonia patterns exhibit similarity based on viridae. 2 Therefore, the imaging findings of coronavirus infection caused by SARS-CoV, MERS-CoV, and SARS-CoV-2 closely resemble each other. The purpose of this pictorial review is to provide imaging spectrums of coronavirus infection and present differences in imaging among them  (2). While the virus enters the cells, its antigen is presented to antigen-presenting cell such as dendritic cell or macrophage (3), which migrates to regional lymph nodes and stimulates the body's humoral and cellular immunity by virusspecific B and T cells (4). Virus-specific B and T cells produce antibodies and release numerous cytokines. Cytokines induce the recruitment of neutrophils and monocyte-derived alveolar macrophage, and these amplify the inflammatory response (5). The exuberant inflammatory response can disrupt the alveolar-capillary barrier, resulting in alveolar flooding and intra-alveolar fibrin accumulation (6). Cytokine storm, which is an uncontrolled systemic inflammatory response resulting from the release of a large amount of pro-inflammatory cytokines, causes acute respiratory distress syndrome and multiorgan failure. These immune responses result in diffuse alveolar damage or organizing pneumonia, which are manifested as ground-glass opacity, consolidation, crazy paving appearance, and reversed halo sign with peripheral predominance on CT (7).

Imaging findings of coronavirus infection
Initial and follow-up chest radiographs (CXR) findings Table 2 summarizes imaging findings of coronavirus infection. Approximately 15%-20% of patients with coronavirus infection have normal initial CXR. [6][7][8] The most common initial CXR findings of coronavirus infection are peripheral focal or multifocal airspace consolidation, ground-glass opacities (GGO), or Initial and follow-up chest CT findings Similar to the CXR findings of coronavirus infection, the CT findings include GGO with or without interlobular septal    BJR Imaging Findings of Coronavirus Infections thickening, consolidation, or a combination of both; these are the most common findings during the first two weeks of coronavirus infection [9][10][11] (Figures 2 and 8-10). In SARS-CoV infection, reticulation is evident after the second week of infection and persists in half of the patients after 4 weeks 9 (Figure 4). In MERS-CoV infection, crazy paving abnormalities and organizing pneumonia (OP) are seen during the second and third weeks of infection 10 ( Figure 5). In SARS-CoV-2 infection, GGO (with or without crazy paving appearance) and consolidation show a decrease in extents, whereas a mixed pattern of GGO and consolidation demonstrates an increase after second week of infection 11 (Figure 11). Cavity, centrilobular nodules ( Figure 12), mediastinal, or hilar lymph node enlargement are rarely seen in coronavirus infection. Pulmonary vascular enlargements in areas of lung opacity can be seen in more than half of the patients with SARS-CoV-2 infection 12 and venous or arterial thromboembolic disease may be complicated in about 30% of critically ill patients with SARS-CoV-2 infection due to excessive vascular inflammation or diffuse intravascular coagulation 13 (Figures 13 and 14).
The location and distribution of parenchymal abnormalities and disease progression patterns are similar to those seen on CXRs. [9][10][11]14 During the early stage of the disease, parenchymal abnormalities are usually located in the peripheral lung; from there, they eventually spread to involve both lungs when the disease progresses ( Figure 10). Parenchymal abnormalities usually have a peripheral and basilar predilection in MERS-CoV infection 10 (Figures 2 and 5), whereas with peripheral or both peripheral and central predilection bilateral multilobe lesions are seen in SARS-CoV-2 infection 11,14 (Figures 2, 9 -11, 13 and 14). In the chronic stage of coronavirus infection, variable-sized GGO with interlobular septal and intralobular interstitial thickenings are the most common findings. Signs of fibrosis such as parenchymal bands, reticulation, traction bronchiectasis, irregular interface signs are also usually seen [9][10][11] (Figures 4, 9, 13 and  15). In SARS-CoV infection, GGO and interstitial opacity in the

Prognostic determinants
Several studies have been conducted to investigate the correlation between imaging findings and clinical outcomes. Higher CT and CXR scores (percentage of lungs or the number of zones involved with opacification), especially in patients with old age and comorbid lung illness, could be used as fatal prognostic indicators in SARS-CoV infection. 5 In MERS-CoV infection, a greater extent of parenchymal abnormalities, pleural effusion, and pneumothorax was associated with poor prognosis and short-term mortality ( Figure 6). 10,16 Although imaging features that help determine the prognosis of SARS-CoV-2 infection are not yet fully understood, older age and progressive consolidation with a greater extent on imaging might suggest poorer prognosis ( Figure 10).

Differential diagnosis
Coronavirus infection is sometimes difficult to distinguish from other viral infections, bacterial pneumonia, or OP associated with other causes. Viral pneumonia in an immunocompetent patient can be divided into bronchopneumonia, OP, and diffuse alveolar damage (DAD) pattern. OP and DAD pattern are common features of coronavirus pneumonia and can be seen during the disease course or in advanced disease. Viral pneumonia showing OP or    It is difficult to differentiate coronavirus infection from other diseases by imaging alone; therefore, clinical manifestation, contact history, and laboratory tests should also be considered to make the final diagnosis.

Role of imaging in coronavirus infection
The main role of imaging in viral infection outbreak is to identify the presence of pneumonia, provide differential diagnosis, and monitor changes of pneumonia with treatment. When deciding which imaging modality to use for establishing a diagnosis or for guiding management in viral infection outbreak, there are several factors to consider; patient's clinical severity, radiation hazard to the patient, accessibility of imaging modalities, possibility of virus transmission to uninfected healthcare workers and other patients, and community infection status. 17 Although it is insensitive in mild or early coronavirus infection, CXR remains the first-line and the most commonly used imaging modality because it is rapid and easily accessible. It is also helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. However, CT lacks equipment portability with imaging performed within an infected patient's isolation room and has a risk of virus transmission along the transport route to a CT scanner and within the CT room. CT can be used when the patient has symptoms but the CXR is normal or there are only questionable abnormalities on CXR. CT is also indicated in patients with functional impairment and/or hypoxemia after recovery from coronavirus infection. Contrast-enhanced CT may be indicated in patients with signs of thrombotic complication. The appropriate use of imaging in each clinical situation should be considered on this basis. 17 concluSionS Although imaging findings of coronavirus infection are nonspecific and have significant overlap among those of SARS-CoV, MERS-CoV, and SARS-CoV-2 infections, they have several important differences. The most common initial CXR and CT findings are GGO and consolidation with peripheral predominance and these lesions eventually spread to involve both lungs as the disease progresses and pulmonary fibrosis may develop after long-term follow-up. Imaging features that help determine the clinical outcome or prognosis of coronavirus infection are the extents of parenchymal abnormalities. The greater extents of parenchymal abnormalities, especially in patients with old age or comorbidity, might suggest poorer prognosis in coronavirus infection, necessitating intensive care unit management, or predicting oncoming succumbing to death.

acknowleDgMent
We gratefully acknowledge Miri Jeong for providing graphic illustration.