**2. Chest manifestations of COVID-19**

SARS-CoV-2 which is acquired through the inhalation route primarily targets the respiratory system. The symptoms attributable to respiratory system include cough, breathlessness, expectoration, sore throat, chest discomfort or pain and hemoptysis. Non-specific symptoms include fever, fatigue, and myalgia [20].

SARS-CoV-2 expresses various spike proteins on its outer surface which avidly binds to angiotensin converting enzyme-2 (ACE-2). ACE-2 is expressed in alveolar pneumocytes and vascular endothelium in abundance. The virus binds to ACE-2 and enters into the cell where it replicates and causes cell death with consequent release of inflammatory cytokines in profusion which cause damage to the host [21, 22].

The primary manifestation of COVID-19 is pneumonia. The pneumonia is usually bilateral and peripheral with a predilection for lung bases. Mild to moderate disease constitutes the bulk of cases (80%) and is characterized by constitutional symptoms and development of mild pneumonia, whereas severe disease occurs in approximately 15% and is generally characterized by more than 50% lung involvement and presents with dyspnea and hypoxia [21]. Critically ill patients constitute a small portion (5%) of infections and present with respiratory failure, shock and multiorgan dysfunction. Apart from affliction of lungs the bronchial tree is also affected by this disease leading to inflammation of bronchial walls [23, 24].

Pulmonary vascular involvement is commonly reported in COVID-19. Frequent involvement of pulmonary vessels is a unique feature of COVID-19 which makes it different from other viral and bacterial causes of pneumonia [18]. Pulmonary embolism frequently occurs in severely ill COVID-19 cases. The underlying mechanisms include the triad of Virchow including hypercoagulability induced by infection and hypoxia, immobility and vascular endothelial injury [25, 26]. However, besides involvement of major pulmonary vessels affection of small pulmonary vessels has been described as a unique distinguishing feature of COVID-19 pneumonia [27].

In various autopsy studies of COVID-19 patients small vessel involvement has been reported to be the hallmark of COVID-19 pneumonia [28]. Small pulmonary vessel thrombosis is commonly found in COVID-19 pneumonia. The putative mechanism put forth to explain this includes immunothrombosis [29]. Vascular

endothelial injury caused by SARS-CoV-2 upon binding with ACE-2, which is expressed abundantly on endothelial cells, leads to severe endothelialitis and thrombosis of these small vessels [28–30].

Cardiac manifestations in COVID-19 include arrhythmias, myocarditis, cardiomyopathy, carcinogenic shock and cardiac arrest and sudden death. Myocarditis and cardiomyopathy has been reported in 7% and 7–33% of severely ill COVID-19 cases, respectively [31, 32]. Myocardial dysfunction evidenced by elevated serum troponin levels is associated with poor clinical outcome. Various mechanisms have been put forth to explain cardiac injury in COVID-19. COVID-19 can cause direct injury to myocardium leading to myocarditis which is a dreaded complication with high mortality [32]. Severe infection can induce plaque rupture and coronary artery thrombosis leading to myocardial ischemia. Infection associated hypoxia and vasoconstriction can affect coronary vessels leading to critical myocardial ischemia and cardiac dysfunction [33]. Alternately, disseminated intravascular coagulation (DIC) induced by severe SARS-CoV-2 infection can precipitate coronary artery thrombosis and cause myocardial infarction [33]. Lastly, stress induced cardiomyopathy can also explain myocardial dysfunction in COVID-19 [34].

### **2.1 Chest X-ray radiography (CXR)**

Chest X-ray radiography (CXR) is the preliminary imaging modality employed in the initial workup of suspected COVID-19 pneumonia cases [35]. CXR has a multitude of unique advantages and limitations. CXR is widely available in almost all health facilities including emergency rooms (ER), intensive care units (ICU) and wards. Due to the small size of equipment it has the advantage of portability which circumvents the transfer of patients away from ICU or wards for performance of imaging thereby minimizing the requirements of staff and chances of spread of infection [35, 36]. CXR equipment is easy to disinfect. CXR entails a small radiation dose to the patient which makes it preferable for children and pregnant patients. Owing to these advantages major medical societies across the world have advocated the use of CXR in the workup of individuals suspected of having COVID-19. American College of Radiology supported the use of CXR for the evaluation of suspected individuals to facilitate triage and monitoring the course of illness [36, 37].

However, CXR has some major limitations. It has a low sensitivity and specificity in the detection of COVID-19 pneumonia. The sensitivity of CXR has been reported in the range of 33–69% [38–40]. CXR is insensitive especially in mild cases and during the early stages of disease [40]. To address the issue of low sensitivity and specificity attempts have been made to take advantage of artificial intelligence by developing deep learning algorithms [41, 42]. Deep learning algorithms have been found to improve the accuracy of CXR in the detection of COVID-19 pneumonia. Most of the patients have a normal CXR during the initial stages of infection, however, with the passage of time the positivity rate of CXR increases. It has been reported that approximately 80% patients will have a positive CXR at some point during the course of hospitalization [43, 44].

A postero-anterior or an antero-posterior CXR is obtained. A slight modification of conventional technique has been made by interposing a glass door between the patient and film to reduce exposure of radiographer to infection [44]. This technique has been found to produce optimal image quality and at the same time minimizing the exposure of radiographer to infection.

The typical findings at CXR include consolidations and ground glass opacification (GGO) with a peripheral and basal predilection (**Figure 1**). Peripheral distribution of pulmonary opacities is one of the specific features of COVID-19 pneumonia [45]. Diffuse lung opacification may be seen in patients with severe disease or acute

#### **Figure 1.**

*CXR in two different RT-PCR confirmed COVID-19 cases showing bilateral ground glass opacification (red arrows in A) and multifocal consolidations (red arrows in B) with lower zone predominance.*

respiratory distress syndrome (ARDS) [46, 47]. Initially the CXR may be normal; however, lung opacities may evolve rapidly reaching a peak at around 6–12 days [48, 49]. Pleural effusion, pericardial effusion and mediastinal lymphadenopathy is seen infrequently in severe cases [44]. The degree of pulmonary opacification on CXR has been reported to predict the need for hospitalization or intubation with patients having GGO in two lung zones more likely to require hospitalization and those with opacification of three or more zones likely to undergo intubation [46]. Bilateral lung involvement is seen commonly (73%) whereas, a unilateral lung involvement is seen less frequently (<25%) [43, 44]. It is a good clinical practice to look beyond lungs when assessing a CXR. Position of tubes (endotracheal tube and nasogastric tube) and lines (central venous line) must be assessed on CXR [46].

The two most common radio-opacities of GGO and consolidation are not specific to COVID-19 and are seen in many other infectious and non-infectious pulmonary pathologies [47, 48]. Non-COVID-19 viral pneumonias like influenza, Middle East Respiratory Syndrome (MERS) and other viral pneumonias must be included in the differential diagnosis in cases of bilateral pulmonary affection [49]. Bacterial pneumonia must be considered in the differential diagnosis particularly in cases of unilateral lung involvement [50]. Non-infectious causes of pulmonary opacities like pulmonary edema, aspiration, pulmonary hemorrhage, inflammation (like pulmonary eosinophilia) and pulmonary vasculitides should be considered in the differential diagnosis in appropriate clinical setting [43, 48].

The British Society of Thoracic Imaging (BSTI) guidelines recommend performance of CXR in all patients with a oxygen saturation of less than 94% and those who do not meet this criterion, CXR should be performed in them when "clinically required" [45]. COVID-19 survivors who recover from acute illness require clinicoradiological follow-up. BSTI guidelines recommend that patients who required ICU or high dependency unit (HDU) admission or were managed as in-ward patients with severe pneumonia should be assessed virtually at 4-6 weeks post-discharge and then face-to-face if needed and subsequently a face-to-face clinical assessment along with a CXR must be undertaken at 12 weeks. Patients who did not require ICU or HDU admission and were managed as mild–moderate pneumonia should undergo a follow-up CXR at 12 weeks [45]. Follow-up CXR are essential to pick any residual lung abnormalities sufficiently early to ensure their management to avert any long-term fibrotic pulmonary sequelae.

### **2.2 Lung ultrasound (LUS)**

Due to its rapidity, easy availability, portability, repeatability and lack of ionizing radiation there has been a resurgent use of LUS in COVID-19 pandemic. It has been used mostly as a complementary and sometimes as an alternative modality in the detection of pulmonary involvement in COVID-19 cases. LUS usage has been particularly rewarding in critically ill patients who need a bedside modality which could circumvent their transfer out of the intensive care unit (ICU) room [46, 47].

The most common imaging features of LUS in pulmonary involvement in COVID-19 include B-lines, thick irregular pleura and subpleural consolidations [46]. B-lines are an imaging surrogate of subpleural interlobular septal thickening which occurs due to accumulation of fluid in pulmonary interstitium and alveolar spaces [48]. B-lines are hyperechoic linear lines, oriented vertically from pleural surface into the depths of lung. These lines spread like rays down the ultrasound screen and maintain their brightness throughout without fading. B-lines may be separate or coalescent. When multiple lines coalesce together they produce what is referred to as shining white lung. B-lines should move or slide with respiratory excursions [49]. Lack of this sliding movement should alert one to consider the possibility of underlying pneumothorax [49].

LUS can be used in emergency room (ER) for prompt detection of pulmonary involvement in symptomatic patients suspected of COVID-19 as soon as they arrive in the ER. LUS features typical of pulmonary involvement will ensure rapid detection, prompt isolation and timely treatment of these patients before RT-PCR results are available [50].

LUS can prove handy in monitoring the course of illness in inward patients by demonstrating the degree of lung involvement. The presence of a few widely separated B-lines in limited areas of chest suggests a mild disease whereas multiple clumped lines spread in multiple chest areas is indicative of a more severe form of disease [50, 51]. Similarly, in ICU setting LUS can help in monitoring the progression of disease and additionally help in detection of complications like pleural or pericardial effusion [51]. LUS can also be used in detection of complications of mechanical ventilation like pneumothorax. Ultrasound can also be used in the diagnosis of arterial and venous thrombosis, a complication which is frequently seen in severe COVID-19 cases [52].

Echocardiography, a specialized form of ultrasound, can aid in detection of cardiac complications of COVID-19 like myocarditis, cardiomyopathy, cardiac failure, intracardiac thrombosis and major pulmonary artery embolism [53]. Echocardiography can be used in this specific disease for the detection of major pulmonary embolism and its prognostication [54]. Detection of thrombus in right heart, right ventricular outflow tract or main pulmonary artery, akinesis of free wall of right ventricle (McConnell's sign), hypercontractility of right ventricular apical wall, dilatation of right ventricle (ventricular diameter of >42 mm at base and > 35 mm at mid-cavitary level) and paradoxical motion of interventricular septum are specific echocardiographic signs of pulmonary embolism [55, 56]. Echocardiography can also detect cardiac dysfunction in myocarditis, myocardial ischemia and cardiac failure [56].

#### **2.3 Computed tomography (CT)**

CT is a cross-sectional imaging modality which uses x-rays projected through multiple angles at the patient to generate an image [22]. The use of CT for the diagnosis and screening of COVID-19 has been universally discouraged by various radiological societies across the world citing reasons such as lack of specificity of CT for precise diagnosis with overlap seen between COVID-19 pneumonia and other viral infections on CT [16, 19]. Secondly, CT entails transfer of patients from wards or ICU to CT suite. Finally there is a possibility that CT suites may act as a vector of cross infection. The consensus guidelines of American College of Radiology (ACR) and European Society of Radiology (ESR) and the European Society of Thoracic Imaging (ESTI) do not recommend performance of CT for the diagnosis or screening of COVID-19 [16, 22, 31]. CT has thus been reserved for a small subset of patients with severe disease, those showing respiratory worsening during illness or to monitor the course of disease. However, in some selected circumstances CT may also be helpful in patients with milder symptoms who have pre-existing comorbidities, such as diabetes mellitus, chronic respiratory disease, obesity, chronic kidney disease etc. [57]. Performance of repeat CTs is not routinely indicated during recovery. However, a repeat CT may be warranted in cases with suspicion of complications likely superadded infection and pulmonary embolism [57].

Notwithstanding the recommendations, CT has been widely performed in COVID-19 cases and has been used to support the diagnosis, assess severity, detect complications, choose appropriate treatment and monitor response to therapy [41]. CT has greatly helped in understanding the natural course of the disease. While CXR is considered the first line tool in the initial screening or assessment of COVID-19 cases, CT is still employed widely owing to its high sensitivity in the detection of pneumonia [43]. In many cases subtle imaging findings which are difficult to detect on CXR are readily identifiable on CT.

Typical CT findings include multifocal and bilateral GGOs and or consolidations with peripheral and lower lobe predominance (**Figures 2** and **3**) [34, 36, 38]. Unilateral lung involvement is less common [43]. On CT, GGO is defined as increased lung attenuation with preservation of underlying vascular and bronchial structures [58]. Consolidation is defined as increased lung attenuation with obscuration of underlying bronchial and vascular structures [58]. Other additional features seen on CT include crazy paving pattern which is a GGO with superimposed interlobular septal thickening producing a pavement like appearance [59, 60]. The relative frequency of type and distribution of lung lesions varies across different studies. A systematic analysis of 34 published studies including 4121 patients revealed bilateral lung involvement in 73% [61]. Multilobar lung involvement was seen in 67% patients. GGOs were seen in 68%, consolidation in 32% and crazy-paving pattern in 35% patients [61]. Additional findings reported were air bronchogram sign (44%), pleural thickening (27%), pleural effusion (5%) and lymphadenopathy (5%) [61]. Some

#### **Figure 2.**

*Axial chest CT images at slightly different levels (A, B) in lung window settings of a 56-year-old COVID-19 patient showing diffuse ground glass opacification in both lungs with a peripheral distribution.*

*Chest Imaging in Coronavirus Disease-19 (COVID-19) DOI: http://dx.doi.org/10.5772/intechopen.98312*

**Figure 3.**

*Coronal chest CT images at slightly different levels (A, B) in lung window settings of a 61-year-old COVID-19 patient showing diffuse ground glass opacification in both lungs with both upper and lower lobe involvement.*

symptomatic patients may have a normal CT, especially during the early stages of disease. Similarly, asymptomatic patients may have an abnormal chest CT [62–64].

CT findings evolve rapidly after symptom onset and reach a peak at around 6–13 days of illness [63]. There is increase in the extent of lung involvement and change in the appearance of pulmonary opacities. GGOs may progress into crazy paving pattern or consolidations [64]. Thereafter the findings may remain stable for some time and then gradually resorb [65]. However, in some cases there may be rapid progression into ARDS [66]. The pulmonary opacities during resolution phase start organizing and lead to secondary organizing pneumonia which manifests as reverse halo or atoll sign and perilobular opacities [61]. In one study nearly half of the patients had residual lung abnormalities consisting of fibrosis 3 months after discharge [66]. Other findings observed on CT include segmental or subsegmental vascular enlargement (defined as greater than 3 mm diameter) within the lung opacities. It has been observed in up to 89% COVID-19 pneumonia [28]. This sign of segmental or subsegmental vascular enlargement is a relatively specific sign of COVID-19 pneumonia with a diagnostic significance [41]. Presence of vascular enlargement sign may help confidently diagnose COVID-19 pneumonia. The underlying pathophysiological mechanism for vascular enlargement sign may be related to severe vascular inflammation, vasodilatory effect of proinflammatory cytokines or small vessel thrombosis [65–67].

Other less common findings observed on CT include reverse halo sign or atoll sign, bronchial wall thickening, nodules and halo sign [34]. Reverse halo sign is defined as a relatively lucent GGO surrounded by a dense ring of consolidation [51]. This finding is typically seen in resorptive stage of the disease. Pleural effusion, pericardial effusion and mediastinal lymphadenopathy is seen infrequently particularly in severe disease [18]. Presence of cavitation or tree in bud nodules are not observed in COVID-19 and should arouse suspicion of an alternate diagnosis. CT has been reported to have a high sensitivity of around 94% in detecting COVID-19 [54]. However, the specificity of CT is limited (39%) [68]. The dominant findings of GGO and consolidation observed in COVID-19 are seen in many other infectious and non-infectious diseases of lung [69, 70]. A comprehensive and detailed clinical information and exposure history is essential during interpretation of CT to increase the diagnostic confidence.

To determine the severity of lung inflammation in COVID-19 and help in identifying the patients in need of special care, severity scoring systems have been devised [71]. Anatomically there are five lobes in two lungs. Each lobe is assessed

individually to determine the degree of pulmonary opacification. Each lobe is scored visually from 0 to 5. A score of 0 is assigned if there is no involvement, score of 1 for <5% involvement, score 2 for 5–25% involvement, score 3 for 26–50% involvement, score 4 for 51–75% involvement and score 5 for >75% involvement. The individual scores of all 5 lobes are added to provide a final CT severity score. CT severity scores of 1–5 are categorized as mild disease, 6–14 as moderate disease and 15–25 as severe disease [71, 72]. The disease severity as determined on CT correlates with short-term clinical outcome with higher CT severity scores associated with worse outcomes [73].

CT imaging features of COVID-19 overlap with many other pulmonary infections, predominantly viral infections, but it also exhibits some characteristic imaging features which are seen infrequently in other infections [65]. The Radiological Society of North America (RSNA) Expert Consensus Statement on Reporting proposed a standardized nomenclature and included four categories to determine the chances of a pulmonary opacity being COVID-19 [74]. The four categories are typical appearance, indeterminate appearance, atypical appearance and negative for pneumonia (**Table 1**) [74]. In March, 2020, the Dutch Radiological Society developed a standardized CT based reporting format known as COVID-19 reporting and data system (CO-RADS) to ensure uniformity in reporting and to improve communication between radiologists and physicians [75]. CO-RADS provides a level of suspicion for lung involvement in COVID-19. The degree of suspicion increases from CO-RADS category 1 (very low suspicion) to CO-RADS-5 (very high suspicion). The two peripheral categories of 0 and 6 are invoked when a CT is technically inferior and insufficient for diagnosis or to label a scan in a patient with positive RT-PCR result for SARS-CoV-2, respectively (**Table 2**) [74–76].

#### **2.4 CT pulmonary angiography (CTPA)**

CTPA has demonstrated pulmonary embolism in up to 30% of COVID-19 patients [61]. The location of these emboli has been reported in main pulmonary artery (22%), lobar pulmonary artery (34%), segmental pulmonary artery (28%) and subsegmental arteries (16%) [77, 78]. In cases with a severe disease with sudden respiratory worsening or hemodynamic instability, CTPA is indicated to detect pulmonary embolism [77]. Pulmonary embolism is a life-threatening complication of COVID-19. However, if diagnosed early and treated appropriately improved outcomes are observed. CTPA entails administration of a bolus of non-ionic iodinated contrast and performance of CT during passage of contrast through the pulmonary vascular tree. To ensure optimal timing of scanning a bolus tracking technique is used. Pulmonary embolism manifests as a filling defect within a contrast filled pulmonary artery [79]. Besides the direct visualization of embolus some indirect signs in lungs and heart can be seen. Pulmonary infarction can be seen as a wedge shaped peripheral consolidation [80]. Similarly, bowing of interventricular septum, dilatation of right ventricle and reflux of contrast into inferior vena cava or hepatic veins may be seen and indicates increased pulmonary artery pressure [80, 81].

#### **2.5 CT perfusion angiography**

Besides pulmonary macroembolism, involvement of pulmonary microvasculature is a unique feature of COVID-19. Micro vascular dysfunction of pulmonary and non-pulmonary organ systems has been widely reported in COVID-19 [66]. It is believed that binding of viral spike proteins to ACE-2 on endothelial cells incites severe endothelialitis and precipitates microthrombosis of these small vessels. This microthrombotic phenomenon also referred to as immunothrombosis has been


#### **Table 1.**

*RSNA expert consensus guidelines for reporting CT in patients suspected of COVID-19.*


#### **Table 2.**

*COVID-19 reporting and data system (CO-RADS).*

confirmed by various autopsy studies [15, 23]. This microthrombotic angiopathy causes obliteration of vascular bed and results in hypoxemia [29]. Non-contrast CT or CTPA cannot detect this condition. The direct visualization of occlusion of micro vascular bed is not possible on CTPA as it is beyond the resolution thresholds of currently available technology [80]. CT perfusion angiography is an advanced CT technology which demonstrates micro vascular thrombosis by detecting pulmonary perfusion defects [81]. However, this technology is limited by its availability. It has been suggested that CT perfusion angiography may also have a role in COVID-19 survivors who demonstrate residual respiratory dysfunction by detecting residual clot burden [82, 83].

#### **2.6 Magnetic resonance imaging (MRI)**

MRI is not recommended for the detection of pulmonary involvement in COVID-19. However, in many cases MRI performed for other indications may accidentally pick up pulmonary changes consistent with COVID-19 [84]. On MRI, pulmonary parenchymal changes of increased signal intensity on both T1-weighted and T2-weighted sequences correspond to GGO and consolidation seen on CXR and CT [84, 85]. MRI has found use in the evaluation of cardiac complications of COVID-19. MRI has the capability to demonstrate changes of myocarditis or ischemia precipitated by COVID-19 infection and also to provide a quantitative measure of various cardiac functional indices [85]. In myocarditis, a diffuse increase in myocardial signal intensity on T2-weighted sequence, increase in T1-relaxation values on T1-mapping can be seen [84]. Post-contrast studies may reveal late gadolinium enhancement in a mid-myocardial or transmural pattern. Cine steady state free precession (SSFE) sequences will reveal regional or global wall motion abnormalities with reduced ejection fraction [86].

## **2.7 Positron emission tomography/computed tomography (PET-CT)**

Although PET-CT is not currently indicated in the management of COVID-19 cases, however, reports of pulmonary findings consistent with COVID-19 have emerged when PET-CT was used for other conditions particularly oncology imaging [87]. The lung opacities of GGO and consolidation demonstrate increased 18-fluorodeoxyglucose (FDG) uptake [88]. Standard uptake values (SUV) of 4.6 to 12.2 have been reported [88]. Increased FDG uptake has also been demonstrated in normal sized mediastinal and hilar nodes in COVID-19. In future, FDG-PET may find use in the monitoring of response to treatment and prediction of recovery as FDG uptake may help determine the degree of residual inflammation [89, 90].
