Mimickers of novel coronavirus disease 2019 (COVID-19) on chest CT: spectrum of CT and clinical features

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a new type of coronavirus that was isolated from respiratory tract samples in the city of Wuhan, Hubei Province, China, in December 2019 [1]. COVID-19 (coronavirus disease 2019) became a highly infectious disease that was officially recognized as a pandemic in March 2020 [2]. More than 49 million patients and 1.2 million deaths of COVID-19 have been reported worldwide by November 10, 2020 [3]. During the rapid spread of SARS-COV-2 globally, diagnostic methods for detecting the virus have many limitations. RT-PCR testing has low sensitivity early in the disease (ranging from 37 to 71%) [4]. CT chest has high sensitivity, but low specificity [4‐7]. This low specificity may stem from the fact that it is difficult to distinguish COVID-19 from other diseases on chest CT [8].

In order to optimize patient management, medical care and disease control, radiologists and chest physicians should be aware of CT chest features that distinguish COVID-19 from other etiologies [9]. The aim of the review is to differentiate between the COVID-19 findings on CT and other mimickers.

Patients infected with COVID-19 usually presents with fever (88.7–98%), cough (67.8–76%) and dyspnea (55%), less commonly headache, fatigue, hemoptysis conjunctival congestion and loss of smell [10, 11]. Abdominal symptoms such as nausea, vomiting and diarrhea are possible [11]. The disease can progress to acute respiratory distress syndrome, metabolic acidosis, septic shock, coagulation dysfunction and multi-organ failure [12]. Laboratory findings in COVID-19 are a decreased lymphocyte count and an increased CRP and high-sensitivity C-reactive protein level [10‐12]. Lymphopenia was reported to be a dependable indicator to categorize the moderate, severe, and critical ill types [13].

COVID-19 patients are classified as having minimal, common, severe and critical illness [12]. Minimal disease patients have subtle clinical symptoms. Common cases have symptoms such as fever and mild coughing. Severe cases are the ones meet any of the following criteria: (1) resting blood oxygen saturation ≤ 93%; (2) respiratory rate ≥ 30 beats/min; or (3) oxygen concentration ≤ 300 mmHg. Critical patients can be affected with one of the following: (1) respiratory failure needing mechanical ventilators; (2) shock; and (3) organ failure requiring intensive care management.

Ground-glass (GGO) pattern with or without consolidation is the most common feature of COVID-19 infections. They are usually bilateral, multifocal and peripheral with posterior or lower lung zone distribution [6, 7, 14‐16]. Ground-glass opacification is defined as hazy increased lung opacity with preserved bronchovascular margins contrary to consolidation that is defined as a homogeneously increased parenchymal attenuation with obscuration of margins of airway and vessel walls [14]. A different unifocal pattern of GGO was reported by Zhou, et al. in early phase of disease, commonly at the inferior lobe of right lung [17]. Furthermore, Bernheim, et al. reported a significant number of cases having opacities of non-specific distribution and non-predominant perihilar pattern [6]. GGO has also been frequently reported to have a “crazy paving” pattern [6, 7, 14, 18] that is defined as thickening of interlobular septa and intralobular lines with superimposed GGO [17, 19]. Vascular dilatation and traction bronchiectasis are typical findings found in the GGO detected in COVID-19 patients [20]. Architectural distortion with the formation of subpleural bands was reported in some cases during a peak stage of the disease [9]. Pulmonary embolism was found among patients with COVID-19 and was linked to elevated D-dimer [21]. Other findings typically were seen in infection as thickening of bronchial wall, mucoid impactions and centrilobular nodules (tree-in-bud), and lymphadenopathy and pleural effusion are rarely observed [6, 14]. Figures 1, 2 and 3, and Additional file 1 demonstrate typical CT features of COVID-19 pneumonia.

CT Findings in patients with COVID-19 vary according to the timing of imaging. A negative CT during first two days after onset of symptoms with GGO usually develops between first and fourth days after symptom onset with the peak at 6–13 days have been reported [6, 9, 18, 22]. The frequency of consolidation, mixed patterns and reversed halo increases later in the disease [6, 9, 18].

The Radiological Society of North America expert consensus proposed four categories to report chest CT findings attributed to COVID-19 (typical, indeterminate, atypical and negative for pneumonia) [11]. Based on this classification, we categorized the mimics into three categories (Table 1): The first and second category based only on similarity to the imaging features of COVID-19 regardless of the differences in clinical course and the third category based on similarity to COVID-19-related clinical manifestations.

The clinical course of viral or bacterial pneumonia may simulate COVID-19; however, CT features such as perihilar predominance, centrilobular / tree in pud nodules, pleural effusion and lymphadenopathy are in favor of viral pneumonia rather than COVID-19. For example, RSV (respiratory syncytial virus) pneumonia was noted to be common in adults who require ICU admission in the winter season; unlike COVID-19, it shows an airway centric distribution, with bronchial wall thickening and tree in bud opacities, consolidation may or may not occur [53]. Varicella-zoster, measles and mumps typically present with multifocal centrilobular nodular infiltration and less commonly GGO (Fig. 13a) [23, 54]. In contrary to COVID-19, hilar lymphadenopathy and pleural effusion are common association with measles. Segmental or lobar consolidation with cavitation is a sign of bacterial pneumonia (Fig. 13b) or coexistence infection with COVID-19 (Fig. 13c). This common radiological appearance mostly cannot be used to predict the causative organism [53].

A broad spectrum of pulmonary conditions demonstrates imaging features that mimic those of COVID-19 and are difficult to differentiate from it. Awareness of these conditions, careful radiologic analysis and attention to the clinical data are required to prevent an erroneous diagnosis that could potentially adversely impact management and patients’ outcome. A correct diagnosis of these conditions may prevent unnecessary hospitalization and reduce strict quarantine measures for all suspected patients that hold significant pressure on healthcare providers and medical infrastructure.