COVID-19 pandemic is a severe and easily transmissible disease exploding all around the world. Chest CT scans play an essential role in the initial and early diagnosis of COVID-19 as it can show positive findings before the initial positive RT-PCR. So, it is important to focus on baseline CT findings and radiologists’ capabilities to differentiate between non-COVID and COVID-19 in the first consultation to provide proper isolation and treatment [12].
Bai et al. [13] cited that radiologists were capable of differentiating COVID-19 from other viral pneumonias by chest CT with high specificity and moderate or varying specificity (24–94%) among 7 different readers from the USA and China, but an easy simple understood system is still needed especially in epidemic areas with poor medical resources and expert radiologists. According to previous studies, COVID-19 is more likely to present with some CT image features compared to non-COVID-19 diseases.
All studies indicate that the main CT feature of COVID-19 pneumonia is the presence of ground-glass opacities (GGO), typically with a peripheral and subpleural distribution. The multiple lobes involvement with basal predominance is reported in the majority of cases with COVID-19 [10].
GGO can result from various pathologies of alveolar filling with water, pus, protein, blood, or cells including viral infections, like COVID-19, as well as bacterial infections [1].
In their study, Luo et al. [14] added some negative points to make a hierarchical diagnosis. As the most of the reported COVID-19 cases show affection of more than 2 lobes of the lungs, only one lobe involvement is considered as a negative scoring point and also the single-lobe affection has been reported in some cases of community-acquired pneumonia.
Many things in the lungs look exactly the same, and due to the tens of entities that contribute to GGO and/or consolidation, it is critical to understand the new and sometimes puzzling clinical presentations emerging in the current COVID-19 pandemic and it is important to have at hand concepts of non-COVID-19 conditions that act as “mimics and chameleons” of the COVID-19 pneumonia.
One of the major differentials of COVID-19 pneumonia is the pneumonia from other infectious causes like bacterial origin. Community-acquired pneumonia is usually characterized by an airspace consolidation affecting one segment or lobe, limited by the pleural surfaces. CT may also show ground-glass pattern, centrilobular nodules, bronchial thickening, and/or mucoid impaction. In the absence of superinfection, COVID-19 pneumonia has very different findings, with no centrilobular nodules or mucoid impactions [15].
In this study, there were 8 cases of atypical bacterial pneumonias, and they showed GGO with consolidative patches like COVID-19, but there were other features rarely seen in COVID-19. A large pneumatocele is seen in staph pneumonia (Fig. 1), unilateral lung affection with consolidative patch and tree-in-bud appearance with cylindrical bronchiectasis (Fig. 1). Also, consolidation confined to the lobes with peribronchial thickening and pleural effusion in Mycoplasma pneumoniae (Fig. 2). There was one case of CT feature typical to COVID-19. CT chest showed bilateral confluent consolidative patches with GGO and crazy-paving appearance, and it was proven H1N1 on PCR test (Fig. 3).
Elicker et al. [16] and Grudzinska et al. [17] stated that in the current epidemic, GGO in patients with fever and respiratory symptoms suggests COVID-19 until proved otherwise, but some pneumonias of other viral causes may show some different signs like H1N1 influenza, with bronchial wall thickening, centrilobular nodules, and a distribution more along the bronchovascular bundles. Pleural effusion, pneumothorax/pneumomediastinum may be present.
There are broad spectra of non-infectious conditions that cause diffuse GGO. In this study, there were 3 cases of cardiac pulmonary edema with cardiomegaly, dilated pulmonary trunk, interlobular septal and peribronchovascular thickening, pleural effusions, and perihilar distribution of ground-glass opacities.
Komiya et al. [18] stated that pulmonary edema (cardiogenic and non-cardiogenic) is one of the most common causes of diffuse GGO characterized by central predominance with sparing of the peripheral portions of the lung contrary to COVID-19. It is associated with other suggestive signs such as bronchovascular bundle thickening, interlobular septal thickening, and pleural effusions.
In this study, there were 3 cases of ARDS, and the diagnosis was based on acute clinical criteria and imaging features of bilateral basal extensive consolidation on the background of GGO in the anterior non-dependent portions of the lungs with bronchial dilatation in the ground glass opacities and crazy-paving appearance (Fig. 4).
Zompatori et al. [19] and Ferguson et al. [20] described acute respiratory distress syndrome (ARDS) diagnosis is based mainly on clinical criteria include lung injury of acute onset, within 1 week of an apparent clinical insult and with the progression of respiratory symptoms, respiratory failure not explained by heart failure or volume overload and decreased arterial PaO2/FiO2 ratio. According to the phase of the disease, in the early phase, CT imaging shows pulmonary opacification: with anteroposterior density gradient with basal dense consolidation on a background of diffuse GGO with normal or hyperexpanded lung in the non-dependent regions.
In this study, there were 5 cases of pulmonary contusions following trauma, they showed scattered GGO, the clue for the diagnosis was the clinical history with the presence of a thin rim of pneumothorax in 2 cases (Fig. 5).
Oikonomou et al. [21] stated that pulmonary contusions follow blunt or penetrating chest trauma and are almost always seen with other chest (and abdominal) injuries, typically seen as focal, non-segmental areas of parenchymal opacification, more common posteriorly, and in the lower lobes usually peripheral. The clinical history of trauma is always a distinguishing feature.
Wallis et al. [22] stated that some of interstitial lung disease (ILD) also involve the alveolar spaces that make an overlap with COVID-19 pneumonia. This includes COP, HP, RB-ILD, sarcoid, PAP, vasculitis, rheumatoid disease, and drug-induced.
In this study, there were 2 cases of cryptogenic organizing pneumonia with multifocal GGO, crazy-paving and consolidation with atoll sign more in the upper lobes and bilateral pleural effusions (Fig. 6). They were mimickers to COVID-19 pneumonia with histopathological results that were helpful for the final diagnosis.
Webb et al. [23] described that the most common HRCT features of cryptogenic organizing pneumonia (COP) with multifocal ground glass opacifications, crazy-paving and/or consolidation, small, ill-defined nodules, bronchial wall thickening, or dilatation. He stated that the reverse halo sign (atoll sign) is seen only in 20% of patients, and it is not considered to be highly specific.
In the current study, there was one case of diffuse alveolar hemorrhage (Fig. 7) with a patient known of SLE and presented with hemoptysis. The predominance of GGO in the upper lobes with subpleural and costophrenic angle sparing as well as the clinical history was the diagnostic clues.
Marten et al. [24] describe intra-alveolar hemorrhage secondary to extensive parenchymal small-vessel vasculitis like that caused by connective tissue disorders like systemic lupus erythematosus (SLE) which is typically diffuse and initially causes more widespread lobular ground-glass opacification with gravity-dependent density progressing to air-space consolidation +/− crazy-paving pattern.
In this study, there were 4 cases of hypersensitivity pneumonitis of both acute (Fig. 8) and subacute phases (Fig. 9). The diagnosis was made by the clinical history of exposure to antigen (Bird Fancier’s Disease), radiological findings with small poorly defined centrilobular nodules, ground-glass appearance in the acute phase or headcheese sign in the subacute phase, lymphocytosis on bronchoalveolar lavage, and reproduction of symptoms following exposure.
Lacasse et al. [25] described that acute hypersensitivity pneumonitis or acute extrinsic allergic alveolitis is usually occurring within few hours after antigen exposure and often recurs with the re-exposure and has the potential to resolve with treatment. In the acute phase, chest CT shows bilateral and symmetric homogeneous GGO (alveolitis) with multiple centrilobular opacities: usually < 5 mm in diameter also may be present with no fibrosis [26].
There were two cases of RB-ILD in this study presented by cough, dyspnea, and shortness of breath. Both were heavy smokers. The diagnosis was made by clinical history of smoking, typical HRCT findings of ground-glass opacities, and centrilobular nodules (Fig. 10) and proved by biopsy in the first case and bronchoalveolar lavage (BAL) findings (the presence of smokers’ macrophages and the absence of lymphocytosis) in the second case.
Mavridou et al. [27] described CT findings of RB-ILD with smoking bronchial wall thickening and centrilobular emphysema in addition to ground-glass opacities with the slight upper zone predominance and ill-defined centrilobular nodules.
In this study, there was one case of pulmonary alveolar proteinosis (Fig. 11). It mimics CT features of COVID-19 pneumonia with bilateral asymmetrical GGO with crazy-paving appearance, and the diagnosis was confirmed by bronchoalveolar lavage.
Holbert et al. [28] stated that crazy-paving pattern of PAP on CT is non-specific occurring in other diseases.
In this study, there was one case of known sarcoidosis presented with cough. CT showed bilateral patchy ground-glass appearance, but the presence of mild bronchiectatic changes of upper lobe predilection, multiple enlarged prevascular, pre/paratracheal, and hilar LNS as well as the clinical history with no fever was the clue for the diagnosis of alveolar sarcoidosis (Fig. 12).
There was one case of acute interstitial pneumonitis (AIP) presented with severe dyspnea and desaturation; she was intubated. CT chest revealed bilateral asymmetric confluent patches of ground glass with crazy-paving appearance mixed with consolidative patches with air bronchogram more in the lower lobes. The presence of LT side mild pneumothorax was uncommon for COVID-19 pneumonia (Fig. 13). Bronchoalveolar lavage and transbronchial biopsy were done after exclusion of infectious cause.
Wittram et al. [29] described AIP or Hamman-Rich syndrome CT findings with ground-glass attenuation: generally tend to be bilateral and symmetrical, traction bronchiectasis (80% of cases during the course of the disease ), and parenchymal architectural distortion of the lung.
There was one patient in this study, presented with dyspnea and low-grade fever with CT chest showing bilateral scattered mainly peripheral consolidative patches with faint GGO, associated bilateral basal interlobular septal thickening with small nodules (Fig. 14). The patient had a history of amiodarone drug intake for 3 years. The patient was COVID-19 negative, and the presence of the pulmonary nodules and interlobular septal thickening was rare features of COVID-19. The case was confirmed by fiberoptic bronchoscopy with BAL and transbronchial biopsy to be amiodarone lung toxicity.
Wolkove et al. [30] stated that amiodarone lung toxicity is more common in patients exposed to amiodarone, usually for at least 6 months with risk factors like age over 60 years and daily dose > 400 mg. It has two main patterns, multiple peripheral GGO and interstitial fibrosis. One of the radiographic appearances of amiodarone pulmonary toxicity is the presence of peripherally located single or multiple pulmonary nodules, or mass-like opacities and may abut the pleura due to localized accumulation of the drug in an area of previous inflammation.
Another entity of diseases that may mimic COVID-19 is eosinophilic lung disease; we had 3 cases of the eosinophilic lung. The first case was Loffler’s pneumonia (Fig. 15). The diagnosis was made due to fleeting opacities (on X-ray done 1 year before the clinical symptoms, there was left lower lobe air space opacity which was resolved on X-ray 6 months later indicating fleeting opacities), elevated eosinophilic count in BAL, peripheral blood eosinophilia, and high IgE level.
Jeong et al. [31] described Löffler syndrome or simple pulmonary eosinophilia on imaging as a fleeting, non-segmental GGO which may be unilateral or bilateral peripheral predominance. Pleural effusions and lymphadenopathy are not features.
The second case of the eosinophilic lung was Churg-Strauss syndrome (Fig. 16) of asthmatic female patient presented with shortness of breath with cough and dyspnea. CT showed multiple consolidative patches with GGO and crazy-paving appearance, moderate right pleural effusion with extrapulmonary manifestations of pansinusitis, and arthritis, and it was confirmed by laboratory results of high eosinophils and IgE.
The etiology of Churg-Strauss syndrome may be allergic or immune pathogenesis for the disease with asthma, eosinophilia, and elevated serum IgE levels. It affects the lung followed by the skin. However, any organ can be involved. The most common thin-section CT findings include sub-pleural ground-glass opacity or consolidation with a lobular distribution, centrilobular nodules, bronchial wall thickening, and interlobular septal thickening and less commonly mediastinal or hilar lymphadenopathy, and pleural or pericardial effusion [31].
The third case of the eosinophilic lung (Fig. 17) was drug rash with eosinophilia and systemic symptoms (DRESS) with a history of drug intake (anticonvulsant), skin rash, fever, cough, and dyspnea. Bilateral confluent consolidative patches with upper lobe predilection, bilateral mild pleural effusions were seen on CT, and the diagnosis was confirmed by peripheral eosinophilia.
The drug rash with eosinophilia and systemic symptoms or DRESS syndrome typically manifests as a skin rash, fever, and lymphadenopathy with variable internal organ involvement and represents a drug-induced hypersensitivity reaction. Chest CT findings are non-specific but may show diffuse multifocal infiltrative opacification [32].
There were 3 cases of bronchial asthma in this study (Fig. 18) presented with bilateral mosaic patches of GGO due to air trapping seen, but there was left upper lobe tree-in-bud, subsegmental atelectasis (due to superadded infection), and bilateral mild basal bronchoectatic changes; such features are uncommon for COVID-19.
In this study, there was a patient with ESRD on dialysis presented with fever and cough. CT showed bilateral high-density ground-glass centrilobular nodules due to metastatic pulmonary calcification occurring in renal failure. Associated left lung consolidative patches with air bronchogram (Fig. 19). The diagnosis was metastatic calcification with superadded bacterial lung infection based on clinical history with laboratory testing.
