Rev Chil Radiol 2020; 26(4) ARTCULO D RVISIN Imaging ...

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ARTÍCULO DE REVISIÓNRev Chil Radiol 2020; 26(4)

Álvarez J, et al. Hallazgos de imagen en Covid-19. Complicaciones y enfermedades simuladoras. Rev Chil Radiol 2020; 26(4): 145-162.*Email: Jaime Álavrez C. / [email protected] sent 01 June 2020. Accepted for publication 17 August 2020.

IntroductionAcute respiratory disease coronavirus 2019 (CO-

VID-19, formerly known as 2019-nCoV) is a highly infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first described in Wuhan, capital of Hubei Province in China in December 2019 and has spread around the world very rapidly1. On January 30, 2020, the

Imaging findings in Covid-19. Complications and mimicking diseases

Jaime Álvarez C.1*, Paula Concejo I.1, Concepción Ferreiro A.1, Esther Gálvez G.1, María Azahara Hoyas G.1, Iñigo Zubiaguirre T.1, Cristian Rodríguez R.1, Wilmar Ocampo T.1, Francisca Sánchez O.1, Manuel Martínez P.1

1. Radiologist, Radiodiagnosis Services, Hospital Universitario Severo Ochoa, Leganés-Madrid, España.

World Health Organization declared a worldwide state of public health emergency, and on March 11 it was declared a pandemic2. As of June 1, 2020, a total of 6,246,042 cases of COVID-19 were already confirmed with 374,452 deaths worldwide, of which 239,638 cases with 27,127 deaths corresponded to cases declared in Spain3.

Hallazgos de imagen en Covid-19. Complicaciones y enfermedades simuladoras

Abstract: Given the current pandemic caused by SARS-CoV-2, the scientific community is making an effort to share knowledge of this emerging disease. To contribute to this effort, we have done a compre-hensive review of the clinical history and imaging tests in patients affected by COVID-19 in our institution, one of the most affected by the pandemic in the Community of Madrid (Spain). The aim of this review is to describe the radiological findings in the lungs and show the most frequent extrapulmonary pathology as well as some entities that may be confused with COVID-19 will be discussed. Radiologists should become familiar with these imaging features of COVID-19 to design specific imaging protocols that allow prompt diagnosis and treatment. Keywords: Complications; COVID-19; Extrapulmonary; Mimickers; Pneumonia; Thrombosis.

Resumen:Ante la situación actual de pandemia producida por el SARS-CoV-2, la comunidad científica está realizando un esfuerzo para compartir el conocimiento de esta enfermedad emergente. Para contribuir a este esfuerzo, hemos realizado una revisión de las historias clínicas y de las pruebas de imagen en pacientes diagnos-ticados de la COVID-19 en nuestro centro, uno de los más afectados por la pandemia de la Comunidad de Madrid (España). El objetivo de esta revisión es describir las alteraciones radiológicas pulmonares y mostrar la patología extrapulmonar más frecuente y entidades simuladoras de la COVID-19. Los radiólogos deben familiarizarse con estas características de imagen de la COVID-19, de forma que se puedan diseñar protocolos de imagen específicos para cada una de ellas de cara a un diagnóstico y tratamiento oportuno.Palabras clave: Complicaciones; COVID-19; Extrapulmonar; Neumonía; Simuladoras; Trombosis.

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La Comunidad Autónoma de Madrid ha sido una deThe Autonomous Community of Madrid has been one of the most affected areas. Of the almost 50 hospitals in the Autonomous Community of Madrid, our center, the Severo Ochoa Hospital, has been one of the ones that has received the largest number of cases, attending a population of 190,000 people and treating 3,562 patients due to COVID -19, of which 2,699 were admitted, quadrupling the maximum number of which the hospital is projected for admitted patients during the pandemic.

We have carried out a review of the medical records and imaging tests performed on patients treated for COVID-19 in our hospital, focusing on the radiological findings of extrapulmonary complications and the detection of associated pathologies. Also included are entities that can mimick COVID-19 involvement in the imaging and cause diagnostic errors.

The review will be structured in the following sections:

1. Patterns of lung involvement. 2. Extrapulmonary involvement. 3. Complications related to a prothrom-botic state (thrombotic and embolic phenomena). 4. Complications related to anticoagulant treatment. 5. Mimicking diseases.

1. Patterns of lung involvementThe new COVID-19 epidemic is mainly associa-

ted with pulmonary disease, although associated pre-existing respiratory comorbidities are one of the least important risk factors compared to hyper-tension, heart disease, obesity, male sex or age4,5. The typical pattern of pulmonary involvement is the presence of peripheral and subpleural ground-glass

opacities in posterior segments of the lower lobes (a fundamental hallmark of COVID-19) with evolution to mainly subpleural subsegmental patchy consolida-tions5. In addition, other forms of involvement have been described, such as the cobblestone-like pattern (crazy paving), the halo sign and the formation of subpleural bands5,6. Figure 1 describes the main radiological patterns on computed tomography (CT) of lung involvement.

2. Extrapulmonary involvementCases of pneumomediastinum and pneumothorax

associated with lung involvement due to COVID-19 have been identified, although the mechanism is unknown. Once these complications are observed, these patients have to be closely monitored be-cause it can be a possible indicator of worsening of the disease. Therefore, early imaging and timely treatment of COVID-19 complications can improve the therapeutic effect and reduce mortality7.

PneumomediastinumSpontaneous pneumomediastinum is defined by

the presence of extraluminal gas in the mediastinum of non-traumatic origin without associated lung di-sease. It is a self-limited condition and the prognosis depends on the underlying cause8. The presence of air in the mediastinum is explained by air dissecting that extends centripetally through the Broncho vas-cular sheaths, serous structures and adipose tissue due to an increase of the intrathoracic pressure that determines alveolar rupture8,9. Alveolar rupture occurs in the presence of elevated intra-alveolar pressure or damage to the alveolar walls.

Figure 1: Typical chest CT patterns of COVID-19 viral involvement: a. Ground-glass opacities. b. Consolidations. c. Cobblestone pattern. d. Halo sign. e. Subpleural bands.

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The chest radiograph is the routine imaging test for the diagnosis of pneumomediastinum visualized as a double line that draws the mediastinal contour. CT is the gold standard test, although it is reserved for doubtful or complicated cases (Figure 2)8.

Lung-protective ventilation, prone position ventilation, sedation, and adequate analgesia are part of the management of patients with COVID 19. Approximately 3.2% of patients require intubation and invasive ventilation at some point in the course of the disease10. Barotrauma occurs as a common complication in patients undergoing mechanical

Figure 2: 65-year-old woman with lung involvement due to COVID-19. On the third day after admission, she presented clinical and laboratory worsening with an increase in LDH and D-Dimer. CT angiography of the chest, mediastinal window (a) and pulmonary (b) evidenced unilateral right pulmonary thromboembolism (arrowhead), pneumomediastinum (arrows) and multifocal diffuse bilateral ground-glass opacities.

Figure 3: A 49-year-old man, obese, with COVID-19 pneumonia, presents sudden onset of dyspnea and elevated D-Dimer. CT angiography of the chest, lung window (a and b) and mediastinum (c); evidence of right unilateral pulmonary thromboembolism (arrowhead), pneumomediastinum (*), subcutaneous emphysema (black arrow), minimal left pneumothorax (white arrow) and multifocal bilateral ground-glass opacities with pulmonary involvement around 50%.

ventilation and central venous catheter insertion, consisting of alveoli rupture as a consequence of pulmonary overexpansion, with alveolar air outflow and finally formation of pneumomediastinum, pneu-mothorax and emphysema (Figure 3)11.

PneumothoraxAn association between COVID-19 and spon-

taneous pneumothorax has been described, but its prognostic importance is unknown12; in our center we did not identify cases of spontaneous pneumothorax.


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Pneumothorax can be primary (with no known un-derlying cause) or secondary spontaneous to pre-existing lung disease. Spontaneous rupture of a subpleural bulla is the most frequent cause of primary spontaneous and most secondary ones are iatrogenic due to aspiration, thoracentesis, and positive pressure. Generally, the visualization of free air in the radiographic study is suffi-cient for the diagnosis, although in small pneumothorax or in critically ill patients, the diagnosis may require CT13.

3. Complications related to a prothrombotic stateAs more is known about the pathophysiology of

COVID-19 infection, some of the associated findings or complications seen in these patients are explained. The infection is related to an identified prothrombotic state and elevated levels of D-Dimer14. It has been postulated that this prothrombotic state is secondary to a release of pro-inflammatory cytokines that induce the activation of endothelial and mononuclear cells with expression of tissue factor that leads to the activation of coagulation and thrombin formation. Free thrombin circulation, not controlled by natural anticoagulants, can activate platelets and cause thrombosis15. Thromboembolic event rates and the use of increased thromboprophylaxis in patients with COVID-19 are therefore a topic of great interest. However, the clinical manifestations of this procoagulant tendency are poorly defined14,15.

Pulmonary thromboembolism (PE)A higher prevalence of pulmonary thromboembo-

lism (PE) has been described in patients affected by COVID-19, up to 23%, with a higher incidence 12 days after the onset of symptoms. No clear as-sociation has been seen between the extent of lung involvement and the risk of developing thrombotic phenomena, but it has been seen in patients with poor clinical evolution of the infection16. In a patient with hypoxia and increasing D-dimer values while the rest of the analytical parameters normalize (ferritin, LDH, C-reactive protein), a complication with PE should be suspected17. Current guidelines recommend chest CT as a diagnostic tool to assess the pattern of involvement and lung extension. However, due to the increasing incidence of PE due to coagulopathy associated with SARS-CoV-2 infection, some authors propose performing chest CT angiography to evaluate the lung and the presence of thrombus (Figure 4)18, as well as to evaluate other complications such as overload of the right cavities (Figure 5) that can result in respiratory distress, especially in those patients with risk factors (patients admitted to the ICU, mechanical ventilation, etc.)16,18.

Initial treatment is usually systemic anticoagu-lation until the thrombus resolves19,20. Thrombolysis or thrombectomy is reserved for patients in shock, hypotension, or with other signs of systemic hypo-perfusion caused by pulmonary embolism; surgery (lobectomy) is only used in those cases where there is no clinical improvement, suspicion of gangrene, massive hemoptysis, or pulmonary necrosis19.

Figure 4: 26-year-old woman with a history of oral contraceptive treatment, symptoms of dry cough and dyspnea (suspected COVID-19 infection), sinus tachycardia, S1Q3T3 ECG pattern and D-Dimer elevation. CT angiography of the chest, mediastinum (a) and lung (b); evidence of bilateral pulmonary embolism with saddle thrombus (arrowhead) and right chamber overload. Faint bilateral ground-glass opacities with pulmonary involvement in around 25% (arrow).

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Aortic floating thrombiAortic floating thrombi (AFT) are a rare entity fre-

quently associated with atherosclerotic and aneurysmal disease21,22. In those patients without arterial vascular disease, due to the high flow and aortic pressure, the presence of AFT is rare, in these cases they are usually associated with hypercoagulable states and hematological diseases, after instrumental procedu-res or steroid treatment. In general, they are more frequent in the descending thoracic aorta, as well as in the aortic arch (Figure 6)21,22,23. The test of choice is CT angiography due to its wide availability and since it allows evaluation of the aorta in its entirety, supra-aortic trunks, as well as the pulmonary vessels and the existence of concomitant embolic ischemic phenomena in other locations21,22. Due to the high embolic risk, treatment is essential, although there is no established protocol, with medical treatment (anticoagulation and thrombolytic drugs) being the first therapeutic option, reserving surgery (thrombectomy, thromboendarterectomy and aortic replacement) or endovascular prosthesis placement for those cases that do not improve with medical treatment or when there are recurrences or those patients with risk factors21,22,23.

Deep vein thrombosis and thrombophlebitisIt is known that ICU patients are at greater risk of

developing deep vein thrombosis (DVT); in the abs-ence of adequate prophylaxis, its general incidence

among hospitalized patients is 0.9%, reaching up to 15% to 32% among ICU patients24,25. This incidence increases in patients with COVID-19 disease, being the most frequent location of the thrombus mainly distal calf muscles and infrapopliteal territories, they are also described in the iliac-femoral-popliteal axis (Figure 7)26.

Acute infections are associated with a transient increase in the risk of venous thromboembolic events27, it is postulated that the production of procoagulant factors such as tissue factor and clot degradation factors such as D-dimer, are possible mechanisms of thrombosis, although a relationship has not been established with DVT26. Another possible favorable factor that could also explain the involvement of the upper extremities, including thrombophlebitis of the external jugular vein (Figure 8) is the use of a con-tinuous positive ventilator pressure in the airways, which can compress the superficial or deep vessels of the upper extremities26; all the patients in our hospital with upper limb involvement were in fact receiving continuous positive pressure therapy, and some of them were users of central lines.

Ultrasound is usually the initial study, especially in patients with central lines. They behave like any thrombosed venous structure. In CT or MRI studies with contrast, the thrombosed vein is enlarged and with peripheral uptake that corresponds to the venous wall28.

Figure 5: A 50-year-old man with cardiovascular risk factors and chronic liver disease presents with a one-week history of cough, mid-thoracic pain, anatomic symptoms, and elevation of the D-Dimer. CT angiography of the chest, mediastinum (a, b) and lung (c); evidence of bilateral pulmonary embolism with saddle thrombus (arrows) and right chamber overload (*). Bilateral ground-glass opacities with pulmonary involvement around 25%.


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Figure 6: 89-year-old male diagnosed with COVID-19 with a torpid progress and increased D-Dimer. CT angiography of the chest, lung window (a); Ground-glass opacities with 50-75% involvement of the lung parenchyma. Mediastinal window axial slice (b) and coronal (c) floating thrombi in aortic arch and descending thoracic aorta (arrows).

Figure 7: 77-year-old man diagnosed with COVID-19 with a torpid progress and increased D-Dimer. Abdominopelvic CT with iv contrast (a.) Filling defect of the common, superficial and deep femoral veins, in relation to DVT. (arrows). Chest CT, lung window (b); Ground-glass opacities with pulmonary involvement around 25%.

Figure 8: 48-year-old woman with no relevant history with symptoms of dry cough and dyspnea (suspected COVID-19 infection) and elevated D-Dimer. Chest CT angiography, mediastinal window (a.) Shows a filling defect in the right anterior and internal jugular vein compatible with thrombosis (arrows). Lung window (b); predominantly multiple parenchymal consolidations are seen in RLL.

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Unfortunately, no data is yet available on the prognosis of patients who develop DVT during a SARS-COV-2 infection, so further studies should investigate how the two conditions interact with each other and their possible impact on recovery. However, considering these preliminary data, our institution administers anticoagulant doses of low molecular weight heparin (LMWH) in hospitalized patients with COVID-19, after monitoring the results of coagulation tests and kidney and liver function26.

Ischemic strokeAlthough ischemic stroke has been recognized

as a complication of COVID-19 (usually with severe disease)29 the mechanisms and phenotype are not yet definitive, although it has been suggested that COVID-19 could stimulate the production of antiphospholipid antibody30 as ischemic stroke mechanism (Figure 9).

Early therapeutic anticoagulation with LMWH could also be beneficial in reducing thromboem-bolism in patients with ischemic stroke associated with COVID-19, but must be balanced with the risk of intracranial hemorrhage, including hemorrhagic transformation of acute infarction31. Early diagnosis

and hyper-acute treatment is the key to minimi-zing mortality and morbidity in patients with acute stroke. “Stroke units” must be aware that COVID-19 patients can present with strokes and must have the appropriate personal protective equipment for each suspected patient32.

Multiple cerebral infarctsThere are emerging global reports of coagulopathy

in the context of COVID-19, including pulmonary embolism, multiple cerebral infarcts (Figure 10), and limb ischemia33. A recent publication identified antiphospholipid antibody in a COVID-19 patient with significant coagulopathy. These antibodies can also arise transiently in patients with critical illnesses and various infections.

The presence of these antibodies can rarely lead to thrombotic events that are difficult to differentiate from other causes of multifocal thrombosis in criti-cally ill patients, such as disseminated intravascular coagulation, heparin-induced thrombocytopenia, and thrombotic microangiopathy30.

It has also been proposed that coagulopathy may portend a poor prognosis in patients with COVID-19 disease.

Figure 9: A 77-year-old man with COVID-19 pneumonia presents symptoms of facial and left brachial paresis. Cranial CT without iv contrast (a). Hypodense cortical subcortical lesion in the right cerebral hemisphere compatible with acute ischemia in the territory of the right middle cerebral artery (*). CT with iv contrast, Willis polygon with 3D reconstruction (b) shows obstruction of the right M2 segment (arrow). Chest CT lung window showing extensive areas of bilateral ground-glass and cobblestone pattern.


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Mesenteric ischemia / ischemic colitisIntestinal ischemia, mainly mesenteric artery

thrombosis and, to a lesser extent, ischemic colitis, is a rare condition that constitutes one of the abdominal emergencies with the worst prognosis and can be a thromboembolic complication secondary to the hyper-coagulable state associated with COVID-19. It presents high rates of morbidity and mortality, therefore, early diagnosis and prompt management are essential34. In this sense, imaging tests have an important role, since neither the symptoms nor the laboratory tests are specific. Currently, CT is the initial imaging technique of choice for the diagnosis of suspected acute intestinal ischemia and, in addition, it allows the exclusion of other causes of acute abdominal pain (Figure 11)35. Finally, the small intestine may also be an important site of entry or interaction for SARS-CoV-2, as ente-rocytes are rich in angiotensin converting enzyme (ACE-2) receptors. Initial gastrointestinal symptoms that appear early in the course of COVID-19 support this hypothesis36.

Ischemic lesions of solid organsRenal infarction is an underdiagnosed entity due

to its non-specific clinical and laboratory presenta-tion. Due to the wide availability of CT, the incidental diagnosis of renal infarctions is increasing, which favors early diagnosis and treatment, thus reducing the time of renal ischemia (Figure 12)37. Due to its low frequency, there is no established treatment protocol. Anticoagulation is insufficient to reduce ischemia, so more aggressive measures such as systemic thrombolysis are chosen, although it increases the risk of bleeding. Endovascular techniques have been

developed for the local administration of thrombolytic agents, as well as mechanical thrombectomy37.

Splenic infarction is the result of the occlusion of a splenic arterial branch, caused mainly by thromboem-bolic disease or by infiltrative hematological diseases. They are classically seen as wedge perfusion defects in the parenchyma, although when they are multiple they can fuse and lose this morphology. The key is the extension of the abnormal parenchyma area to the intact capsule (Figure 13). Acute infarcts can be complicated by superinfection, subcapsular hema-tomas, or splenic ruptures. A chronic infarct loses volume with focal atrophy and can calcify38.

4. Complications related to anticoagulant treatmentAnticoagulants, such as heparin sodium and LMWH,

are currently used for the treatment and prevention of thromboembolic disease secondary to COVID-19 involvement. Bleeding is estimated to be an often serious complication of anticoagulant therapy, in up to 4% of treated patients39. Gastrointestinal bleeding is a frequent form of complication that usually subsides after correcting the coagulation state. Other frequent forms of serious hemorrhagic complications are the abdominal wall hematoma, especially of the muscular compartments of the rectum sheath (Figure 14) or the iliopsoas muscle (Figure 15) with opening to the retroperitoneum (Figure 16), both of which are those, that with greater frequency require urgent percuta-neous treatment.

Risk factors include, in addition to anticoagulation for the prothrombotic state induced by COVID-19, specific comorbidities (severe heart disease, liver dysfunction, kidney failure, hypertension, cerebrovascular disea-

Figure 10: 56-year-old male, SARS-CoV-2 positive, admitted to the ICU due to severe respiratory failure, after removal of sedation, left hemiparesis with asymmetric reflexes was clear. Cranial CT without iv contrast (a and b). Ischemic lesion in the territory of the right middle cerebral artery and left posterior cerebral artery. PA chest radiograph (c) shows bilateral peripheral patchy opacities in both hemithorax.

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Figure 11: A 70-year-old man with COVID-19 lung involvement, presents with acute abdominal pain, rectal bleeding, increased CRP and D-dimer. Abdominal CT with iv contrast, lung window in the middle fields shows extensive and bilateral ground-glass involvement predominantly posterior. Section at the level of the mesogastrium (b) and coronal MPR reconstruction (c) shows circumferential thickening of the wall of the left colon with increased attenuation of the adjacent fat suggestive of ischemic colitis.

Figure 12: A 78-year-old man with pulmonary involvement due to COVID-19, presents with acute abdominal pain, impaired kidney function and elevated D-Dimer. Abdominal CT with iv contrast (a). Left renal infarction (arrow). Lung window at the level of the lower fields shows a cobblestone pattern, subpleural bands and bronchiectasis.

Figure 13: A 70-year-old man with COVID-19 parenchymal involvement, presents with acute abdominal pain, fever, and D-Dimer elevation. Abdominal CT with iv contrast. Middle field lung window shows extensive and bilateral ground-glass involvement. Soft tissue window section in the upper hemiabdomen (b) and coronal MPR reconstruction (c) showing splenic triangular hypodensity compatible with infarction (arrow).


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Figure 14: 57-year-old woman with pulmonary involvement due to COVID-19, massive PTE and treatment with heparin, sudden drop in hemoglobin. Abdominal CT with iv contrast, lung window (a) shows patchy areas of ground-glass. In abdominal slices (b) hematoma in the anterior rectus muscle and the left obliques of the abdomen (*) extending to the pelvis that depends on the left inferior epigastric artery. Pre and post embolization angiography (c and d) of active bleeding from the left lower epigastric artery (Arrows).

Figure 15: A 71-year-old man with COVID-19 lung involvement and right unilateral PE under treatment with LMWH at anticoagulant doses, presents with hypotension and a decrease of 3 mg / dl in hemoglobin. Abdominal CT without iv contrast. (a) Hematoma of the ilio-psoas muscle (*) on the left side. Lung window in the middle fields (b) shows a cobblestone pattern in the right hemithorax, predominantly posterior. Pre-embolization arteriography (c) of active artery bleeding left distal lumbar (Arrows), (d) post treatment with embolization liquid.

Figure 16: A 57-year-old woman with a history of AF, admitted for pulmonary involvement due to COVID-19 and anticoagulant treatment for right DVT, presents with hypotension and a decrease of 4 mg / dl in hemoglobin. Abdominal CT with iv contrast (a). Extensive hematoma of the left psoas (*) with increased attenuation of retroperitoneal fat. Lung window in middle fields (b) showing predominantly peripheral pulmonary consolidation in both lower lobes and patchy areas of ground-glass density. Arteriography pre (a) and post-embolization (b) of active bleeding of the left distal lumbar artery and iliopsoas artery (Arrows).

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se, and patients receiving long-term hemodialysis), use of concurrent medications (mainly non-steroidal anti-inflammatory agents and diuretics), duration of treatment, intensity of anticoagulant effect, and age of the patient40. The diagnostic method of choice is abdominal CT since, in addition to assessing the size and location of the hematoma, it verifies the existence of active bleeding and identifies the artery causing the bleeding. In the event of failure of conservative treatment or hemodynamic instability, endovascular treatment is indicated for embolization of bleeding41. In low-location hematomas of the rectus sheath, em-bolization of the ipsilateral inferior epigastric artery is usually sufficient to control bleeding (Figure 14d), while those of high location sometimes require dis-tal embolization of the ipsilateral internal mammary artery. In the case of spontaneous retroperitoneal hematomas, the arteries involved are the lumbar arteries and the iliolumbar artery (Figures 15d, 16d). The use of liquid/adhesive materials is recommen-ded, whose therapeutic effect is independent of the patient’s coagulation status42.

5. Mimicking diseasesA wide variety of CT findings have been described

in lung involvement in COVID-19 disease. However, all studies indicate that the main characteristic on lung CT is the presence of ground-glass opacities, typically with a peripheral and subpleural distribu-tion, with involvement of multiple lobes, particularly the lower lobes1,43,44,45. The ground-glass pattern represents either an interstitial (interstitial thicke-

ning) or an alveolar (partial occupation of alveoli) process and is a common manifestation of multiple lung diseases. In this review we describe a series of entities with characteristics of ground-glass opacity on pulmonary CT that can mimick lung parenchymal involvement in COVID-19, such as pulmonary edema, diffuse alveolar hemorrhage, non-specific interstitial pneumonia (NSIP), hypersensitivity pneumonitis (HP), atypical pneumonias, radica (radiation) pneumonitis, metastasis, etc.

Pulmonary edemaPulmonary edema is a very common cause of

diffuse ground-glass opacity, but it is characterized by a perihilar predominance and in the basal regions of the lower lobes, usually symmetric and with preservation of the peripheral portions of the lung, unlike COVID-19. It is associated with other suggestive signs, such as septal thickening that reflects the dilated lymphatic vessels and thickening of the interlobular septa (Figure 17). A common finding that supports this diagnosis is associated pleural effusion, frequently bilateral46.

Hemorragia alveolar difusaDiffuse alveolar hemorrhage is an emergency that is

defined as the presence of blood in the alveolar spaces. It occurs due to damage in the pulmonary microcirculation (capillaries, arterioles and alveolar venules) and can be of pulmonary origin, for example, in infection or of a systemic cause as occurs in systemic vasculitis. Clinically, it can manifest as hemoptysis, dyspnea, acute-onset cough, and anemia47,48. It is also characterized by perihilar and

Figure 17: An 81-year-old man with multiple cardiovascular risk factors, consultation for cough and progressive dyspnea for 2 weeks (suspected SARS-CoV-2 infection). CT angiography of the chest, mediastinum window (a) and lung (b), shows cardiomegaly, ground-glass opacity of perihilar distribution, thickening of fissures and bilateral pleural effusion.


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bilateral ground-glass opacities of sudden onset and that progressively converge respecting the vertices and the periphery of the lungs, without having a subpleural predominance (Figure 18). In the acute phase, it can be indistinguishable from pulmonary edema or diffuse lung infection49. At 48-72 hrs after the episode, a reticular pattern is produced and if there is no recurrence of bleeding, the image can return to normal within 1-2 weeks.

Nonspecific interstitial pneumonia (NSIP)Nonspecific interstitial pneumonia (NSIP) is an

interstitial disease that affects the lung parenchyma of unknown etiology. The prognosis of this entity is better than that of other interstitial diseases such as the usual interstitial pneumonia (UIP) or desquamative interstitial pneumonia (DIP). Chest CT is the imaging test of choice for its study since in most cases the chest X-ray is normal50. It is characterized by a ground-glass

pattern in a peripheral location with involvement of the middle and lower fields (Figure 19). Sometimes we see a clear improvement in the imaging findings after steroid treatment. If the disease progresses, ho-neycombing or traction bronchiectasis can be seen50.

Hypersensitivity pneumonitisHypersensitivity pneumonitis (HP), also known

as extrinsic allergic alveolitis, is a granulomatous in-flammatory disease of the lungs caused by inhalation of antigenic organic fumes or particles51. In the case of the bird keeper’s lung, they are particles that are usually found in the epithelium, the dust that covers the feathers or the feces of birds52. The disease can present as an acute, subacute or chronic disease. Acute and subacute HP episodes generally resolve after cessation of antigen exposure once the diagno-sis is established; Corticosteroids are used in early

Figure 18: 48-year-old woman with symptoms of fever, dyspnea and mild hemoptysis, peripheral blood smear compatible with acute leukemia. PA chest x-ray on admission (a) shows LUL and retrocardiac opacities. Portable control chest X-ray at 1 hour (b) shows radiological worsening. Chest CT, lung window (c), shows ground-glass opacities and consolidation. Interlobular septal thickening is not observed. Finding compatible with acute diffuse alveolar hemorrhage, given the clinical context.

Figure 19: Woman with polymyosistis and diagnosis of NSIP under treatment with corticosteroids, consultation for cough without dyspnea (suspected SARS-CoV-2 infection). Previous lung CT from December 2018, without iv contrast. Lung window in lower fields (a) Fine reticular pattern and ground-glass with basal distribution without fibrotic component. Lung CT at entry to the level of upper (b) and lower (c) fields, discrete reticular pattern probably residual and inconclusive for COVID-19, with preservation of upper fields.

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stages to accelerate healing or in severe or advanced stages that can be progressive and irreversible51. On chest CT, the combination of a mosaic pattern with areas of ground-glass and centrilobular nodules is highly suggestive of the diagnosis (Figure 20)53. A careful environmental and occupational history and establishment of exposure to a known inciting antigen are key players in making the diagnosis of HP.

Atypical pneumoniaThe group of atypical pneumonia is made up of

pneumonia caused by viruses, Pneumocystis jirovecii, and atypical bacteria (Legionella pneumophila, Myco-plasma pneumoniae, and Chlamydia pneumoniae). On chest CT, atypical pneumonias produce bilateral, extensive and often symmetrical pulmonary alterations with a ground-glass pattern54.

Pneumocystis jirovecii pneumonia was the most common infection in patients with Acquired Immuno-deficiency Syndrome (AIDS), but it has been replaced by bacterial infection since the introduction of its pro-phylaxis. Non-HIV patients typically present more acute symptoms with fever and hypoxemia, while HIV patients frequently present a prodrome of 2-3 weeks with low-grade fever, weight loss, dyspnea, and malaise. The most common finding on CT is ground-glass opacities with a symmetrical distribution, a predominance of the upper lobes having been described (Figure 21). This finding may be associated with other alterations including consolidations, septal thickening, and thin-walled cysts that can lead to spontaneous pneumothorax. Definitive diagnosis requires identification of the organism from respiratory specimens with fluorescent antibody staining or polymerase chain reaction (PCR)56.

Post-Actinic PneumonitisRadiotherapy-induced lung damage manifests

itself differently radiologically, depending on the time elapsed since the completion of treatment. In the early stages, between 1 and 3 months after radiotherapy; in the late or chronic phases, developed later and with stabilization over 12-15 months, the findings are called radica (radiation) fibrosis. It occurs in <1% of cases and is dose dependent, being constant from 40 Gy57. It manifests as cough and dyspnea 3 months after receiving radiotherapy, although the time of onset is variable. Not only is CT better able to delineate paren-chymal changes, but it often demonstrates localized changes in the irradiated field, facilitating diagnosis. The two most common findings are ground-glass opacities and / or airspace consolidation (Figure 22)58.

Lung metastasesThe typical radiological findings of pulmonary

metastases consist of multiple nodules of varying size and diffuse thickening of the interstitium (Figure 23). Ground-glass opacity around the mass (halo sign on chest CT) can be seen when fragility of neovascular tissue leads to vessel rupture, as in metastases from choriocarcinoma and angiosarcoma, as well as tumor growth along the alveolar walls as in adenocarcinomas of gastrointestinal tract tumors59.

Carcinomatous lymphangitis Carcinomatous lymphangitis constitutes a pattern

of tumor spread through the pulmonary lymphatic ves-sels, being a factor of poor prognosis in terms of the response to chemotherapy and survival. 80% of cases are caused by adenocarcinomas, the most common

Figure 20: 47-year-old man with dyspnea on moderate exertion, 2 weeks, (suspected SARS-COV-2 infection). Epidemiological history of contact with birds. PA chest radiograph (a) shows diffuse opacities in upper and middle fields. Axial chest CT (b) Ground-glass opacities associated with centrilobular ground-glass nodules predominantly in upper fields. PA chest radiograph (c) Radiological improvement of the pulmonary pattern after administration of corticosteroids. Finding compatible with HP.


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tumors being the lung, breast, colon and stomach60. Chest CT findings include smooth or nodular thicke-ning of the interlobular septa and thickening of the peribronchovascular and subpleural interstitium, as well as mediastinal and hilar adenopathy, and pleural effusion (Figure 24). It can occur both unilaterally and bilaterally61.

Calcified lung nodulesCalcified multiple pulmonary nodules occur in a

wide variety of diseases, and on chest radiographs they may mimic localized patchy pulmonary opaci-ties. There are multiple processes that condition the appearance of calcified pulmonary nodules (Figure 25). Thus, they appear in the reparative phases of inflammatory processes (TB, chickenpox), benign and malignant tumors (hamartomas, Epithelioid heman-gioendothelioma, metastasis), inhalation diseases (pneumoconiosis of coal workers and silicosis), me-tabolic diseases (kidney failure, hypercalcemia) and processes of unknown origin (alveolar microlithiasis)62.

ConclusionRadiological imaging plays a very relevant role

in the diagnosis and follow-up of patients with CO-VID-19 disease. The most common findings on chest radiographs and chest CT include multifocal bilateral ground-glass opacities and predominantly periphe-rally distributed irregular consolidations. In addition to pulmonary involvement, it is relevant to identify other associated findings, such as extra-parenchymal pulmonary involvement, complications secondary to the prothrombotic state given the high incidence of thrombotic and embolic phenomena, as well as hemo-rrhagic complications due to anticoagulant treatment. Likewise, entities that begin with a pulmonary pattern in ground-glass opacities should be included in the differential diagnosis. All of these features can aid rapid diagnosis, guide clinical decision-making, and monitor the progression of COVID-19 disease. Special attention should be paid to the role of radiologists in the fight against this new infectious disease.

Figure 21: A 32-year-old man with moderate exertion dyspnea for 3 weeks, (suspected SARSCOV-2 infection). Epidemiological history of HIV with severe immunosuppression. PA chest radiograph (a) shows diffuse pulmonary opacities. Axial chest CT (b) Ground-glass opacities associated with symmetrical distribution of centrilobular ground-glass nodules. PCR-coronavirus (negative) and PCR- Pneumocystis jirovecii (positive).

Figure 22: A 57-year-old woman with a history of infiltrating ductal carcinoma of the right breast. In the 8th week after the completion of radiotherapy, she presented with symptoms of dyspnea and cough for 2 weeks (suspected SARS-CoV-2 infection). Chest CT, lung window (a) shows ground-glass opacities in the upper right anterior lobe (Arrow).

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Figure 23: A 72-year-old man with a history of renal carcinoma undergoing chemotherapy with cough and dyspnea for 3 days (suspected SARS-COV-2 infection). PA chest radiograph (a) shows faint opacities in LLL and LUL (arrows). CT of the chest, lung window and MPR reconstruction in coronal (d) and axial (d) planes, shows multiple nodules in both hemithorax suggestive of metastasis.

Figure 24: 57-year-old woman with a history of infiltrating ductal carcinoma of the right breast and carcinomatous lymphangitis. CT angiography of the chest, mediastinal window (a) and lung window (b) shows nodular fissure thickening (arrowhead) and interlobular septa, ground-glass opacities or consolidation (*) with a right unilateral distribution. Bilateral pleural effusion is also seen (Arrow).

Figure 25: 30-year-old woman with no relevant history with one-week symptoms of cough and general malaise (suspected SARS-COV-2 infection). PA chest radiograph (a) shows multiple subcentimeter pulmonary nodules in both hemithorax predominantly in the upper lobes. CT chest reconstruction MPR coronal (b) and axial (c) lung window confirms these findings.


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