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Viral

KEY FACTS

TERMINOLOGY CLINICAL ISSUES • typically affect respiratory epithelium • Cold: Upper symptoms (tonsillopharyngitis, , , , otitis IMAGING media, and conjunctivitis) • Radiography • syndrome: Abrupt , , , and ○ May be normal at presentation (20%) malaise ○ Focal or multifocal consolidation • Acute in infants and children: Wheezing with • CT/HRCT concomitant signs of respiratory viral ○ Mosaic attenuation and expiratory air-trapping • High rate of viral infection in patients with community- ○ Ground-glass opacity and consolidation acquired pneumonia (2-35%) ○ Nodules, micronodules, and tree-in-bud opacities DIAGNOSTIC CHECKLIST • Interlobular septal thickening • Bronchial &/or bronchiolar wall thickening • Diagnosis relies on clinical suspicion: Host risk factors, presentation, and exposure history TOP DIFFERENTIAL DIAGNOSES • Lobar consolidation uncommon in viral pneumonia • • Nodules < 10 mm, may exhibit CT halo sign, and do not • Aspiration exhibit cavitation • Diffuse alveolar hemorrhage • Branching or centrilobular nodules and mosaic perfusion • Organizing pneumonia common in viral bronchiolitis

(Left) Coronal HRCT of a patient with acute infectious bronchiolitis secondary to respiratory syncytial (RSV) shows diffuse bilateral tree-in-bud nodules and upper lobe ground-glass opacities. RSV is a common cause of infectious bronchiolitis and has been linked to in children. (Right) Coronal HRCT of a 52-year-old woman with pneumonia shows multifocal ground-glass opacities bilaterally. are the predominant cause of the but occasionally cause viral pneumonia.

(Left) Axial NECT of a 75-year- old man with pneumonia shows multifocal ground-glass opacities and consolidations. Herpes pneumonia is rare but may occur in the setting of burns, transplantation, pregnancy, malignancy, and human immunodeficiency virus infection. (Right) Axial CECT of a 71-year-old woman with pneumonia shows bilateral consolidations ﬈ and a small right ﬉. Human metapneumovirus is a common cause of viral pneumonia.

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TERMINOLOGY • Middle east respiratory syndrome (MERS) ○ Acute viral caused by novel virus Definitions currently named MERS (MERS-CoV) • Pulmonary viral infection typically affects respiratory DNA Viruses epithelium from to terminal bronchioles • Adenovirus ○ Alveolar involvement less common, but often severe and rapidly progressive ○ 5-10% of acute respiratory in infants and children, but < 1% of respiratory illnesses in adults RNA Virus-Related Diseases ○ Swyer-James-MacLeod syndrome: Acquired constrictive • Influenza bronchiolitis due to childhood ○ Seasonal community infections, endemic infections, and • Varicella virus unpredictable pandemics ○ Common contagious infection in childhood, increasing ○ Influenza type A: Most important respiratory virus frequency in adults affecting general population with regards to morbidity – Varicella pneumonia: 1 of every 400 cases of and mortality adulthood infection ○ Major cause of respiratory illness in • (CMV) immunocompromised hosts ○ CMV infection: > 70% of hematopoietic stem cell • (H5N1) transplant (HSCT) recipients; ~ 1/3 develop CMV ○ Contact with infected birds; usually poultry pneumonia ○ Overall case fatality rate exceeds 60% – Infection during postengraftment period (30-100 days • Swine influenza (H1N1) after transplantation) ○ 1st pandemic of 21st century, originally reported in • Epstein-Barr virus (EBV) Mexico (spring of 2009) ○ Primary infection manifests as ○ High transmission among humans, but virulence not ○ EBV pneumonia: Rare in immunocompetent or greater than that observed with seasonal influenza immunocompromised subjects • Parainfluenza virus ○ Associated with development of , ○ Common cause of seasonal upper respiratory tract , infection in adults and children ○ Parainfluenza virus type 3: Respiratory illness in IMAGING immunocompromised hosts and solid transplant Radiographic Findings recipients • Variable and overlapping appearance • Respiratory syncytial virus (RSV) ○ Normal at presentation (20%) ○ Ubiquitous cause of respiratory infection • Tracheobronchitis ○ Most frequent viral cause of lower respiratory tract ○ Bronchial wall thickening infection in infants ○ : Discoid to segmental (mucus plugs) • Human metapneumovirus (hMPV) • Pneumonia ○ Implicated in 4-21% of infants with acute bronchiolitis ○ Focal consolidation: Peripheral, mid, and lower lung – Symptoms clinically indistinguishable from those zones (40%) elicited by RSV ○ Unilateral or patchy bilateral areas of consolidation ○ 4% of cases among patients with community-acquired pneumonia (CAP) or chronic obstructive pulmonary ○ Diffuse consolidation disease (COPD) exacerbations • Complications • ○ Bacterial superinfection: Sudden worsening, cavitation, ○ One of 3 major infectious diseases worldwide or enlarging pleural effusion – 1.5 million childhood deaths per year • Uncommon findings • , echovirus, and enterovirus ○ Hilar or mediastinal lymphadenopathy: Measles and infectious mononucleosis ○ Lower respiratory tract infection may occur sporadically and is not always associated with pneumonia ○ Splenomegaly: Infectious mononucleosis • Human T-lymphotropic virus type 1 (HTLV-1) • Cardiac enlargement (pericardial effusion): Hantavirus ○ Etiologic retrovirus of adult T-cell leukemia or lymphoma • Pleural effusion – Associated with myelopathy, Sjögren syndrome, and ○ Rare except for adenovirus, measles, hantavirus, HSV-1 lymphocytic CT Findings • Hantavirus • Alterations of parenchymal attenuation ○ Rodent-borne zoonotic disease ○ Patchy heterogeneous pulmonary attenuation (mosaic – Hantavirus pulmonary syndrome: Severe acute attenuation pattern) respiratory distress syndrome (ARDS), rapid clinical – Bronchiolar obstruction (inflammation or cicatricial progression, and high mortality scarring) and secondary vasoconstriction • Severe acute respiratory syndrome (SARS) □ Inspiratory/expiratory CT: Differentiation of ○ caused by newly discovered SARS- bronchiolar from pulmonary vascular disease associated coronavirus (SARS-CoV) in 2002 (Guangdong, China) 7 Viral Pneumonia

□ Bronchiolar disease (air-trapping): Decreased • Acute interstitial pneumonia attenuation on inspiration, accentuated on ○ Diffuse alveolar thickening by edema and mononuclear expiration cells, airspace fibrinous exudate &/or hyaline membranes □ Vascular disease: Little increase in attenuation or ○ CMV, hantaviruses (hantavirus pulmonary syndrome), decrease in volume SARS, and MERS • Ground-glass opacity and consolidation • Endothelial damage to small vessels (focal hemorrhagic ○ Coexistence of interstitial thickening and partial airspace necrosis, mononuclear infiltration of alveolar walls, and filling alveolar fibrinous exudates): Varicella-zoster virus ○ Consolidation: Patchy and poorly defined () vs. focal and well-defined (lobar CLINICAL ISSUES pneumonia) Presentation • Nodules, micronodules, and tree-in-bud opacities • Most common signs/symptoms ○ Nodules 1-10 mm in diameter common in viral infections ○ Clinical syndromes – Centrilobular nodules – Cold: Upper respiratory tract symptoms □ Inflammation, infiltration, or fibrosis of surrounding (tonsillopharyngitis, pharyngitis, epiglottitis, sinusitis, interstitium and alveoli otitis media, and conjunctivitis) – Tree-in-bud opacities: Indicative of small airways – Influenza syndrome: Abrupt fever, headache, disease myalgias, and malaise □ Dilatation of centrilobular bronchioles with lumina ○ Acute bronchiolitis in infants and children: Wheezing impacted with mucus, fluid, or pus with concomitant signs of respiratory viral infection – Branching or centrilobular nodules and mosaic – RSV (most common), adenovirus, influenza, and perfusion: Common in viral bronchiolitis parainfluenza – Miliary nodules ○ CAP: , sputum, or dyspnea with fever or □ Nearly any organism; typically tuberculosis, fungi, abnormalities at physical examination (rhonchi and rales) varicella-zoster virus – Influenza and RSV • Interlobular septal thickening □ Comorbidities or risk factors: Smoking, COPD, ○ Widespread with associated ARDS asthma, diabetes mellitus, malignancy, heart failure, • Bronchial &/or bronchiolar wall thickening neurologic diseases, narcotic and alcohol use, and ○ Inflammatory exudates and bronchiolar wall thickening chronic liver disease from edema and smooth muscle hyperplasia • Clinical profile ○ Role of biomarkers DIFFERENTIAL DIAGNOSIS – Procalcitonin: ↓ with viral infection,↑ with bacterial Bacterial Pneumonia infection, • Consolidation, cellular bronchiolitis ○ Better quality of diagnostic tests have improved ability • May exhibit cavitation to detect multiple viruses Aspiration Demographics • Basilar predominant cellular bronchiolitis • Increasingly frequent cause of pulmonary disease • Esophageal abnormalities, neurological and deglutition worldwide disorders • High rate of viral infection in CAP (2-35%) ○ Influenza, hMPV, and RSV: 2/3 of all viral pathogens in Diffuse Alveolar Hemorrhage patients with CAP • Ground-glass opacities ± interlobular septal thickening Natural History & Prognosis (crazy-paving pattern) • No of infection • Variable prognosis ○ Complete resolution in immunocompetent individuals Organizing Pneumonia • Peripheral or peribronchial consolidation DIAGNOSTIC CHECKLIST • Migratory pulmonary opacities Image Interpretation Pearls • Reversed halo sign • Lobar consolidation uncommon in viral pneumonia PATHOLOGY • Nodules < 10 mm, may exhibit CT halo sign; do not exhibit cavitation Microscopic Features • Branching or centrilobular nodules and mosaic • Nodules contain infected cells with cytoplasmic inclusions: perfusion/attenuation common in viral bronchiolitis Cytomegalovirus, adenovirus, herpesvirus • Necrotizing &/or bronchiolitis and diffuse SELECTED REFERENCES alveolar damage (DAD): Influenza, RSV, parainfluenza 1. Franquet T: Imaging of pulmonary viral pneumonia. Radiology. Jul;260(1):18- viruses 39, 2011 • Bronchiolitis and : Adenovirus 2. Kim EA et al: Viral in adults: radiologic and pathologic findings. • Necrotizing bronchopneumonia, multicentric areas of Radiographics. 22 Spec No:S137-49, 2002 hemorrhage (centered on airways): Herpes simplex virus 8 Viral Pneumonia

(Left) Axial HRCT of a bone marrow transplant recipient who developed parainfluenza virus 3 pneumonia shows scattered bilateral ground- glass opacities ﬈. Influenza, respiratory syncytial virus, rhinovirus, and parainfluenza virus are the most common pathogens in this patient population. (Right) Axial CECT of a woman with influenza virus A pneumonia shows extensive, bilateral, peripheral ground-glass opacities and consolidations. The pattern is reminiscent of organizing pneumonia, which is often present histologically.

(Left) Axial NECT of a patient with cytomegalovirus pneumonia and a history of bilateral lung transplantation shows a left upper lobe nodule ﬈ with surrounding ground- glass opacity ﬉, the so-called CT halo sign, which often correlates with perilesional hemorrhage. (Right) Axial NECT of a hematopoietic stem cell transplant recipient with cytomegalovirus infection shows multiple random lung nodules measuring < 10 mm, with surrounding ground-glass opacity ﬈. These findings are highly suggestive of a viral infection.

(Left) Axial CECT of a 28-year- old man with fever and a skin rash due to varicella-zoster virus infection shows profuse, miliary, 1- to 2-mm nodules scattered throughout the lung. (Right) Axial NECT of a patient with hantavirus pulmonary syndrome shows diffuse symmetric ground-glass opacities with superimposed linear and reticular opacities exhibiting the crazy-paving pattern and small bilateral pleural effusions ﬉. The findings were related to . (Courtesy A.S. Sousa, MD.)

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