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Private Tour Guide to Pediatric Coronavirus Disease of 2019 and Multisystem Inflammatory Syndrome in Children in 10 Minutes

What Thoracic Radiologists Need to Know

Foust, Alexandra M. DO*; Winant, Abbey J. MD*; Restrepo, Ricardo MD; Liszewski, Mark C. MD; Plut, Domen MD, PhD§; Lee, Edward Y. MD, MPH*

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doi: 10.1097/RTI.0000000000000565
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Abstract

The coronavirus disease of 2019 (COVID-19) has resulted in dramatic changes worldwide as evidenced by the incorporation of previously esoteric terms such as “corona,” “COVID,” and “social distancing” into daily vocabulary. The rapid evolution and widespread reach of this novel viral infection has triggered an explosion of scientific research globally, resulting in thousands of publications examining all facets of the disease. Filtering through the plethora of existing literature to identify clinically relevant information is time consuming and often impractical for practicing thoracic radiologists with busy clinical schedules. Thus, the goal of this article is to highlight key pieces of information related to pediatric COVID-19 and multisystem inflammatory syndrome in children (MIS-C) for practicing thoracic radiologists.

WHAT IS COVID-19?

COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a zoonotic single-stranded RNA virus belonging to the β-coronavirus cluster, which also includes the coronaviruses responsible for the prior severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS) pandemics.1 The SARS-CoV-2 virus is predominantly spread via respiratory droplets, and once inhaled, it binds to the ACE2 receptors of alveolar epithelial cells, where it replicates and subsequently immobilizes or destroys the host cell, resulting in alveolar damage.2 Viral-induced downregulation of ACE2 production has also been implicated in COVID-19-related immune dysregulation, altered cardiac contractility, and pro-thrombotic state.2,3

WHAT ARE DIFFERENCES BETWEEN PEDIATRIC COVID-19 AND ADULT COVID-19

As of July 18, 2020, pediatric patients (ages 0 to 17 y) account for 6.5% of COVID-19 infections (over 180,000) reported in the United States.4 Overall, children demonstrate a milder clinical course compared with adults and account for only 0.3% (327) of COVID-19-related deaths in the United States.4,5 This difference may relate to lowered expression of ACE2 receptors in nasal and bronchial tissue in pediatric patients as well as differences in immune system maturity.6

Co-infection with SARS-CoV-2 and other viral or bacterial infections has been reported in pediatric patients with greater frequency and can complicate both diagnosis and treatment in these patients.7–11 The most frequently reported pediatric co-infection is Mycoplasma pneumoniae, a bacteria that lacks a cell wall and is a common culprit in cases of pediatric pneumonia not responding to typical antibiotic therapy.5,8,10,12 Notorious for its variable imaging appearance, mycoplasma pneumonia in pediatric patients most frequently presents with lobar or segmental consolidation, focal reticulonodular opacity, or parahilar peribronchial opacity.13 The most helpful features in distinguishing it from COVID-19 pneumonia are a segmental or lobar distribution of consolidation or the presence of a pleural effusion.13

From an imaging perspective, COVID-19 pneumonia in pediatric patients differs from adults in a few important ways. First, pediatric COVID-19-infected patients have been shown to have a lower rate of positive computed tomography (CT) findings, demonstrate fewer total pulmonary lesions, and have involvement of fewer pulmonary lobes compared with adults.14,15 Although a peripheral and subpleural predominant pattern of parenchymal involvement is observed across all age groups, pediatric patients demonstrate a peribronchial distribution and bronchial wall thickening more frequently than adults.14 Although bilateral lung parenchymal abnormality is observed in 73.8% to 78.2% of adult patients, the split between unilateral (56.2%) and bilateral (43.8%) disease in children is much closer.8,16,17 The “halo” sign, defined as a rounded consolidative opacity with a surrounding rim of ground-glass opacity, can be a helpful imaging finding in pediatric COVID-19 and has been reported in up to 50% of cases, although is less commonly reported in adult COVID-19 pneumonia.1,10 Alternatively, air bronchograms observed in 44% to 46% and crazy-paving pattern in 15% to 35.6% of adult patients are infrequently reported across studies of pediatric COVID-19 infection.16–18

WHAT THORACIC RADIOLOGISTS SHOULD KNOW ABOUT PEDIATRIC COVID-19

COVID-19 pneumonia in pediatric patients presents as unilateral or bilateral peripheral (subpleural) and/or posterior, and lower lobe-predominant ground-glass opacities with or without consolidation.19–21 For the purposes of radiology reporting, the typical imaging appearance has been defined as bilateral, as the specificity for unilateral opacity significantly decreases, hence falling to an indeterminate category (Fig. 1).21 The “halo” sign, in a nonimmunocompromised patient, is also considered a typical finding when present, given its relatively narrow differential (Fig. 1).21 Imaging findings including segmental or lobar consolidation, centrilobular nodules (including tree-in-bud nodularity), cavitation, pleural effusion, and/or lymphadenopathy are uncommon findings in pediatric COVID-19 pneumonia and thus, when present, should raise consideration for alternative diagnoses.21

FIGURE 1
FIGURE 1:
A 15-year-old female patient with no significant past medical history who presented with shortness of breath and tachypnea and was found positive for SARS-CoV-2 by RT-PCR. A, Frontal chest radiograph shows bilateral peripheral and lower lung-predominant ground-glass opacities and consolidation. The cardiac silhouette is mildly prominent; however, the patient did not have underlying cardiac dysfunction. B and C, Axial chest CT images on lung window setting demonstrate bilateral peripheral predominant ground-glass and consolidative opacities in the posterior segments of the upper lobes and lower lobes bilaterally. Nonspecific ground-glass opacity is also present in the right middle lobe (C).

Chest imaging is currently not recommended for COVID-19 screening in pediatric patients, and RT-PCR remains the gold standard for diagnosis.21 Similarly, chest imaging is not generally indicated for pediatric patients with known or suspected COVID-19 pneumonia presenting with mild clinical symptoms unless the child has risk factors for disease progression or develops worsening clinical symptoms.21 However, for pediatric patients with moderate-to-severe clinical symptoms, chest radiography can be used as an initial imaging examination regardless of COVID-19 status.21 Chest CT is not recommended as the initial diagnostic test for pediatric COVID-19 although may be considered for assessment of symptomatic children demonstrating a worsening clinical course and/or not responding to supportive therapy owing to superimposed infection or complications.20,21 Evidence for use of lung ultrasound (US) in pediatric COVID-19 pneumonia is scarce, although a few small case series have described pleural irregularity, vertical artifact, confluent B lines (echogenic vertical lines that arise from the pleura and move with sliding lung), and subpleural consolidation in pediatric patients.22,23 As such, the role for the use of ultrasound in management of pediatric COVID-19 is not yet clear.

WHAT THORACIC RADIOLOGISTS SHOULD KNOW ABOUT MIS-C?

MIS-C, a postviral inflammatory syndrome identified in pediatric patients with prior COVID-19 infections, is another important topic for radiologists to be familiar with. MIS-C is diagnosed in patients under 21 years of age with evidence of current or recent SARS-CoV-2 infection (positive RT-PCR, serology, antigen testing, or exposure to suspected or confirmed COVID-19 case within past 4 wk) who present with fever (subjectively or ≥38°C for ≥24 h), laboratory evidence of inflammation, and severe illness involving ≥2 organ systems and requiring hospitalization which cannot be plausibly explained by an alternative diagnosis.24 The clinical severity of MIS-C is generally much greater than acute pediatric COVID-19 pneumonia, with up to 80% of MIS-C cases requiring ICU level care, 20% requiring mechanical ventilation support, and vasoactive medication support in 48% to 76% of cases.25,26 Cardiovascular involvement is frequent including myocardial dysfunction (51% to 58%), reduced ejection fractions (38% to 71%), and more rarely coronary artery dilation or aneurysms (8% to 17%) (Fig. 2).25–29

FIGURE 2
FIGURE 2:
A 9-year-old female patient who presented with 5-day history of fever, abdominal pain, and diarrhea and was admitted to the PICU with hypotension, altered mental status, palmar rash, and conjunctivitis. RT-PCR testing for COVID-19 was negative; however, serum IgG was positive, and the patient was diagnosed with MIS-C. Echocardiogram image (A) at admission shows ectasia of the left main coronary artery (arrow). Follow-up echocardiogram image (B) after treatment with aspirin, IVIG, and methylprednisolone demonstrates interval resolution of the left main coronary artery ectasia (arrow).

From an imaging perspective, MIS-C differs from typical pediatric COVID-19 pneumonia. Chest radiographs may be normal or may show findings associated with cardiac dysfunction and fluid overload such as perihilar interstitial thickening and/or opacities, cardiomegaly, and pleural effusions (Fig. 3).28,30,31 Chest CT may show basal consolidation or diffuse ground-glass opacities, mild hilar adenopathy (rare in acute COVID-19 pneumonia), pleural and/or pericardial effusion, and if cardiac imaging is performed, coronary artery dilatation, or less commmonly coronary artery aneurysms, in some cases.28 Chest CT angiography may demonstrate lobar or segmental pulmonary emboli (Fig. 4).31 Although not reported in the literature to date, the authors have observed at least one case of large airway involvement with supraglottic edema (Fig. 5). In addition, a small case series of pediatric cardiac MRI found diffuse interstitial edema (increased T2/STIR signal) in the left ventricle without evidence of delayed myocardial enhancement.32 In the abdomen, the most frequently observed findings include ascites, right lower quadrant inflammatory change (mesenteric fat stranding, lymphadenopathy), bowel wall thickening, hepatomegaly, echogenic kidneys, and gallbladder sludge, pericholecystic fluid, and findings of acalculous cholecystitis (Figs. 6, 7).28,31,33 Musculoskeletal abnormalities, such as synovitis, can be also seen (Fig. 8).

FIGURE 3
FIGURE 3:
A 9-year-old female patient with history of asthma who presented with fever, hypotension, left ventricular dysfunction, and dilated left anterior descending coronary artery and diagnosed with MIS-C following positive anti-SARS-CoV-2 serology. Frontal chest radiograph shows cardiomegaly with prominent central vasculature and retrocardiac consolidation.
FIGURE 4
FIGURE 4:
A 15-year-old obese female patient without other underlying comorbid medical conditions who presented with shortness of breath and found to be positive for anti-SARS-CoV-2 IgM and diagnosed with MIS-C. Axial CT angiogram of the chest demonstrates a pulmonary embolism (arrow) in the right lobar pulmonary artery.
FIGURE 5
FIGURE 5:
A 14-year-old female patient who presented with dysphagia and subsequently diagnosed with MIS-C. Sagittal CT of the neck demonstrates supraglottic edema (arrow).
FIGURE 6
FIGURE 6:
A 9-year-old female patient with history of obesity who was admitted to the ICU with fever, hypotension, and cardiac dysfunction and diagnosed with MIS-C following positive anti-SARS-CoV-2 serology. A, Transverse gray-scale ultrasound image of the right upper quadrant demonstrates gallbladder sludge (arrowhead). B, Axial enhanced CT of the abdomen and pelvis shows right lower quadrant lymphadenopathy (arrows) with surrounding fat stranding.
FIGURE 7
FIGURE 7:
A 16-year-old female patient with no comorbid medical conditions who presented with diarrhea and was subsequently found to be positive for SARS-CoV-2 and diagnosed with MIS-C. Axial (A) and sagittal (B) contrast-enhanced CT images of the abdomen and pelvis demonstrate circumferential bowel wall thickening and adjacent fat stranding of the descending colon (arrows).
FIGURE 8
FIGURE 8:
A 5-year-old male patient with no comorbid medical conditions presenting with fever and limping who was found to be positive for SARS-CoV-2 and diagnosed with MIS-C. Sagittal gray-scale sonographic image of the left hip (A) shows an anechoic hip effusion (arrow) with adjacent synovial thickening consistent with synovitis. Comparison sagittal gray-scale image of the right hip (B) is normal.

CONCLUSION

As the COVID-19 pandemic continues to evolve, it is important for practicing thoracic radiologists to stay up to date on relevant imaging findings in pediatric patients (Table 1). The current flood of literature on this subject can be overwhelming and difficult to navigate. Therefore, this article has been designed to highlight clinically relevant pediatric COVID-19 and MIS-C-related imaging information into a digestible and easily navigated manner (Table 2).

TABLE 1 - Top 5 Take Home Points for Thoracic Radiologists on Pediatric COVID-19 and MIS-C
Pediatric COVID-19 pneumonia presents as unilateral or bilateral peripheral (subpleural) and/or posterior and lower lobe-predominant ground-glass opacities (GGO)± consolidation
The “halo” sign, peribronchial distribution, and bronchial wall thickening are more frequently observed in pediatric COVID-19 pneumonia, whereas adult patients are more likely to demonstrate air bronchograms and crazy-paving pattern
Chest imaging is not recommended as a screening tool for pediatric COVID-19 pneumonia; however, chest radiographs may be considered in pediatric patients presenting with moderate-to-severe clinical symptoms or who have mild symptoms with risk factors for deterioration. Chest CT should be reserved for assessment of symptomatic children demonstrating a worsening clinical course and/or not responding to supportive therapy owing to superimposed infection or complications
MIS-C is a post-COVID-19 infection-related viral inflammatory syndrome resulting in multiorgan involvement including cardiac dysfunction with potential circulatory collapse, respiratory failure, and gastrointestinal findings predominantly localized to the right lower quadrant
Chest radiographs in MIS-C may be normal or demonstrate signs of cardiac dysfunction including perihilar interstitial thickening and/or opacities, cardiomegaly and pleural effusions. Chest CT may show basal consolidation or diffuse GGO, mild hilar adenopathy, pleural and/or pericardial effusion, coronary aneurysm and lobar or segmental pulmonary embolism. Right lower quadrant inflammatory change (fat stranding, lymphadenopathy, or bowel wall thickening) and ascites are the most frequent abnormalities on abdominal imaging

TABLE 2 - Either Lines Separating the Three Categories or Else an Additional Space Between the Categories Would Make This Less Confusion
Adult COVID-19 Pediatric COVID-19 MIS-C
Pulmonary manifestations Bilateral GGO±consolidation in peripheral and lower lobe predominant distribution Air bronchogram “Crazy-paving” pattern Unilateral or bilateral GGO ±consolidation Peripheral and lower lobe predominant distribution Possible peribronchial distribution Bronchial wall thickening “Halo” sign Perihilar interstitial thickening or opacities Possible ARDS31
Pleural manifestations Pleural thickening15,16 Possible pleural irregularity on ultrasound Pleural effusion
Cardiovascular manifestations Pulmonary Embolism34 Luminal dilation or mural thickening of pulmonary vessels35 Possible cardiomegaly or pericardial effusion (infrequent)35 None known at this time Cardiomegaly Pericardial effusion Pulmonary embolism
ARDS indicates acute respiratory distress syndrome; GGO, ground-glass opacities.

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    Keywords:

    pediatric; coronavirus disease of 2019; multisystem inflammatory syndrome in children; imaging findings; chest radiography; computed tomography

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