Coronavirus disease 2019 (COVID-19) has evolved into a rapidly growing pandemic, with over 462,000 confirmed patients and >20,800 lives claimed as of March 26, 2020.¹ COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and manifests with mild to moderate symptoms in the majority of the patients.² Advanced age and preexisting medical conditions have been reported as the major contributors to disease severity, complications, and mortality.^2–4 The severity of symptoms and risk of mortality are significantly higher in the elderly, particularly those over 60 years of age according to the World Health Organization⁵ and over 65 years of age according to the Center for Disease Control and Prevention.⁶ In a study by Zhou et al,⁷ 48% of COVID-19 patients had at least 1 comorbid condition, among which hypertension (30%) and diabetes (19%) were the most frequent comorbidities. The risks of infection and complications are increased in patients with underlying medical conditions, such as coronary heart disease, hypertension, malignancies, diabetes mellitus, asthma, chronic lung disease, human immunodeficiency virus infection, liver disease, and chronic kidney disease.^5,7,8 Since early in the course of the outbreak, a growing number of studies addressed various clinical and diagnostic imaging features of the disease. Computed tomography (CT) has been confirmed by multiple studies as a highly sensitive modality for the diagnosis of pulmonary involvement of COVID-19 in the early stages of the disease.⁹ The typical features of COVID-19 in chest CT include bilateral, peripheral, and multifocal ground-glass opacities (GGOs) with or without superimposed consolidations^10,11 (Fig. 1). Atypical chest CT findings include cavitary lesions, pleural effusion, pulmonary nodules, bronchiectasis, lymphadenopathy, and pericardial effusion.^9,12 Although the imaging features of COVID-19 are well characterized, there is a paucity of information on chest CT diagnosis of COVID-19 in patients with preexisting systemic or pulmonary conditions. Some pathologies with extensive pulmonary involvement may obscure or obliterate the typical manifestations of COVID-19, whereas others may resemble the atypical or rare CT manifestations of this viral pneumonia. Therefore, the diagnosis of COVID-19 in such patients can be challenging. Due to the low specificity of chest CT findings for COVID-19, the final diagnosis cannot be made solely on the basis of imaging and it is critical to consider the disease processes that may resemble the imaging features of this viral pneumonia. In patients with underlying comorbidities, the differential diagnoses should be formulated collectively on the basis of the pretest probability of COVID-19 infection, reverse transcription polymerase chain reaction test results, and the possible complications related to the underlying conditions.¹² For instance, in a patient with leukemia, drug toxicity due to chemotherapeutic agents should be taken into consideration, whereas this diagnosis will not be considered in an otherwise healthy individual. Another scenario is when COVID-19 is suspected in an immunosuppressed patient who is also at an increased risk of pneumocystis pneumonia. This review summarizes the chest CT features and diagnostic challenges related to COVID-19 imaging in patients with underlying cardiothoracic conditions.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Underlying respiratory system diseases are among the important comorbidities in patients with COVID-19 and have been associated with increased disease severity, complications, and mortality.^13–15 The morbidity and mortality of respiratory tract infections are significantly higher in patients with COPD.¹⁶Figures 2 and 3 demonstrate the chest CT images of 2 known cases of COPD with laboratory-confirmed COVID-19, suggesting that some chest CT findings in patients with superimposed COVID-19 can be inconsistent with the typical features of the disease. On the basis of the current literature, pulmonary cavity formation in COVID-19 is rare and atypical. However, in patients with COPD, small emphysematous bullae are occasionally surrounded by GGOs and may appear as “pseudocavities” (Fig. 2). In Figure 3, there are bilateral patchy GGOs and early consolidations in lower lobes with a peripheral distribution that may mimic aspiration pneumonia or dependent atelectasis.

INTERSTITIAL LUNG DISEASE (ILD)

In patients with ILD, the imaging findings of COVID-19 pneumonia can be subtle and hardly distinguishable from the underlying ILD. Differentiation of COVID-19 infection from lung parenchymal infiltration is quite challenging. Many published cases of COVID-19 pneumonia have resembled nonspecific interstitial pneumonia (NSIP) because both tend to have peripheral and basilar GGOs.^9,17 Hypersensitivity pneumonitis is another possible mimic that may present with a ground-glass appearance in chest CT. Therefore, imaging diagnosis of superimposed COVID-19 pneumonia in such patients should be made on the basis of the clinical context and the mentioned differential diagnoses are to be taken into account. CT images of a known case of well-controlled dermatomyositis with laboratory-confirmed COVID-19 are illustrated in Figure 4. Subpleural GGOs and early consolidations in this patient were suggestive of COVID-19. Although the pulmonary involvement in patients with polymyositis-dermatomyositis may uncommonly manifest as usual interstitial pneumonia, it usually presents as NSIP. As NSIP may present as GGOs, it can be difficult to differentiate it from typical lesions of COVID-19. Figure 5 illustrates the chest CT images of a COVID-19 patient with ILD and usual interstitial pneumonia pattern including honeycombing and cyst formations, tractional bronchiectasis, and peribronchovascular thickening. Some patchy GGOs in this patient could be suggestive of superimposed COVID-19 infection, although acute exacerbation and active fibrosing alveolitis remain within the differential considerations. The presence or absence of bronchiectasis may be helpful in distinguishing fibrosis from COVID-19 pneumonia. However, early cases of ILD may not yet have developed bronchiectasis.

CARDIOVASCULAR DISEASES

A meta-analysis of 46,248 cases demonstrated that hypertension, diabetes, and cardiovascular diseases constitute the most common comorbidities in patients with COVID-19.¹³ These underlying conditions are associated with higher severity of the symptoms in infected patients.^7,18 Viral respiratory infections are generally associated with a relatively poor prognosis in patients with coronary heart disease. Development of heart failure or exacerbation of preexisting heart failure, arrhythmia, and acute cardiovascular injury have been reported as potential consequences of COVID-19 and other types of viral pneumonia.^7,18 Older age, underlying cardiac disease, and severity of pneumonia are associated with a higher risk of myocardial infarction in patients with pneumonia.¹⁹

Patients with chronic heart failure (CHF) may suffer from an accelerated course of pulmonary infection leading to severe respiratory failure.²⁰ Some chest CT manifestations of CHF may mimic the rare, atypical, or ominous presentations of COVID-19. Figure 6 represents the chest CT images of a laboratory-confirmed case of COVID-19 with an ejection fraction of 35% and a history of CHF, hypertension, and diabetes mellitus. The distribution of GGOs and consolidations in this patient are typical for COVID-19 pneumonia. However, the bilateral pleural effusion in this patient, which is most likely due to the underlying CHF, has rarely been reported in patients with COVID-19. Interlobular septal thickening in this patient is most likely due to the cardiogenic pulmonary edema subsequent to the underlying CHF. This finding might be accentuated in patients with concomitant COVID-19 and underlying CHF and should be interpreted in the context of clinical findings.^21,22 Conversely, interlobular septal thickening is a finding in progressed or complicated COVID-19 pneumonia and may suggest pulmonary edema impending acute respiratory distress syndrome.^9,23

MALIGNANCY

It has been suggested that the risk of COVID-19 infection is increased in patients with malignancy and these individuals are more likely to need intensive care and invasive ventilation due to their compromised immune system.^14,24 Furthermore, these patients may demonstrate typical chest CT features of COVID-19, but with atypical or subclinical symptomatology at presentation. Figure 7 demonstrates the chest CT scans of a patient who was under diagnostic workup for a lymphoproliferative disorder. During the course of her inpatient workup, she developed a high-grade fever with respiratory distress and later tested positive for COVID-19. Chest CT findings in this patient consisted of typical features of COVID-19 pneumonia superimposed on preexisting pathologies. Therefore, this case underlines the important role of interval changes in the differential diagnosis of patients with underlying pulmonary pathologies. In this case, the differential diagnosis would also include drug toxicity as a complication of chemotherapeutic agents.

In a distinct scenario, CT findings suggestive of malignancies may be found during the imaging workup of patients with COVID-19. Figure 8 demonstrates the chest CT images of a patient with typical features of COVID-19 pneumonia. In this patient, an apical spiculated mass was incidentally found, which was suggestive of bronchogenic carcinoma. Ominous neoplastic lesions can be missed between other patchy or mass-like consolidations (the satisfaction of search as a source of misdiagnosis). The chances of missing a malignant GGO are higher than that of a spiculated mass, as low-grade primary lung adenocarcinomas can mimic GGOs that are typically seen in COVID-19. Because follow-up chest CT is not performed routinely in these patients, these findings may remain unnoticed. Hence, even in quite typical cases of COVID-19 pneumonia, each parenchymal abnormality must be carefully assessed. However, the superimposition of COVID-19 pneumonia on chest CT manifestations of cancer may render the interpretations problematic. Figure 9 illustrates the chest CT images of a COVID-19 patient with metastatic breast cancer. In this patient, peripherally located patchy GGOs and consolidations are suggestive of superimposed COVID-19 pneumonia. However, these findings are hardly distinguishable from the quite abnormal metastatic parenchymal background. In this case, lymphangitic carcinomatosis should be considered as an important differential diagnosis as septal thickening that is seen in this condition is also commonly found in COVID-19 patients.

CONCLUSIONS

Patients with underlying medical conditions such as COPD, cardiovascular disease, and malignancies are at higher risks of complications and mortality during the course of COVID-19. Some imaging features in these subgroups can be rather unique and the interpretation should be made in the context of clinical findings.^21,22 We addressed some of the diagnostic challenges and essential considerations in chest CT examination of COVID-19 patients with preexisting cardiopulmonary conditions. Although this article is primarily focused on underlying pulmonary diseases that can obscure the chest CT presentation of COVID-19 or resemble its atypical features, it is also important to consider the disease processes that resemble the typical features of COVID-19.