Viral Pneumonia

KEY FACTS

Terminology

• •Viruses typically affect respiratory epithelium

Imaging

• •
  Radiography

  • ○
    May be normal at presentation (20%)
  • ○
    Focal or multifocal consolidation
• •
  CT/HRCT

  • ○
    Mosaic attenuation and expiratory air-trapping
  • ○
    Ground-glass opacity and consolidation
  • ○
    Nodules, micronodules, and tree-in-bud opacities
• •Interlobular septal thickening
• •Bronchial &/or bronchiolar wall thickening

Top Differential Diagnoses

• •Bacterial pneumonia
• •Aspiration
• •Diffuse alveolar hemorrhage
• •Organizing pneumonia

Clinical Issues

• •Cold: Upper respiratory tract symptoms (tonsillopharyngitis, pharyngitis, epiglottitis, sinusitis, otitis media, and conjunctivitis)
• •Influenza syndrome: Abrupt fever, headache, myalgias, and malaise
• •Acute bronchiolitis in infants and children: Wheezing with concomitant signs of respiratory viral infection
• •High rate of viral infection in patients with community-acquired pneumonia (2-35%)

Diagnostic Checklist

• •Diagnosis relies on clinical suspicion: Host risk factors, presentation, and exposure history
• •Lobar consolidation uncommon in viral pneumonia
• •Nodules < 10 mm, may exhibit CT halo sign, and do not exhibit cavitation
• •Branching or centrilobular nodules and mosaic perfusion common in viral bronchiolitis

TERMINOLOGY

Definitions

• •
  Pulmonary viral infection typically affects respiratory epithelium from trachea to terminal bronchioles

  • ○
    Alveolar involvement less common, but often severe and rapidly progressive

RNA Virus-Related Diseases

• •
  Influenza

  • ○
    Seasonal community infections, endemic infections, and unpredictable pandemics
  • ○
    Influenza type A: Most important respiratory virus affecting general population with regards to morbidity and mortality
  • ○
    Major cause of respiratory illness in immunocompromised hosts
• •
  Avian influenza (H5N1)

  • ○
    Contact with infected birds; usually poultry
  • ○
    Overall case fatality rate exceeds 60%
• •
  Swine influenza (H1N1)

  • ○
    1st pandemic of 21st century, originally reported in Mexico (spring of 2009)
  • ○
    High transmission among humans, but virulence not greater than that observed with seasonal influenza
• •
  Parainfluenza virus

  • ○
    Common cause of seasonal upper respiratory tract infection in adults and children
  • ○
    Parainfluenza virus type 3: Respiratory illness in immunocompromised hosts and solid organ transplant recipients
• •
  Respiratory syncytial virus (RSV)

  • ○
    Ubiquitous cause of respiratory infection
  • ○
    Most frequent viral cause of lower respiratory tract infection in infants
• •
  Human metapneumovirus (hMPV)

  • ○
    Implicated in 4-21% of infants with acute bronchiolitis

    • –
      Symptoms clinically indistinguishable from those elicited by RSV
  • ○
    4% of cases among patients with community-acquired pneumonia (CAP) or chronic obstructive pulmonary disease (COPD) exacerbations
• •
  Measles

  • ○
    One of 3 major infectious diseases worldwide

    • –
      1.5 million childhood deaths per year
• •
  Coxsackievirus, echovirus, and enterovirus

  • ○
    Lower respiratory tract infection may occur sporadically and is not always associated with pneumonia
• •
  Human T-lymphotropic virus type 1 (HTLV-1)

  • ○
    Etiologic retrovirus of adult T-cell leukemia or lymphoma

    • –
      Associated with myelopathy, Sjögren syndrome, and lymphocytic pneumonitis
• •
  Hantavirus

  • ○
    Rodent-borne zoonotic disease

    • –
      Hantavirus pulmonary syndrome: Severe acute respiratory distress syndrome (ARDS), rapid clinical progression, and high mortality
• •
  Severe acute respiratory syndrome (SARS)

  • ○
    Atypical pneumonia caused by newly discovered SARS-associated coronavirus (SARS-CoV) in 2012 (Guangdong, China)
• •
  Middle east respiratory syndrome (MERS)

  • ○
    Acute viral respiratory disease caused by novel virus currently named MERS coronavirus (MERS-CoV)

DNA Viruses

• •
  Adenovirus

  • ○
    5-10% of acute respiratory infections in infants and children, but < 1% of respiratory illnesses in adults
  • ○
    Swyer-James-MacLeod syndrome: Acquired constrictive bronchiolitis due to childhood adenovirus infection
• •
  Varicella virus

  • ○
    Common contagious infection in childhood, increasing frequency in adults

    • –
      Varicella pneumonia: 1 of every 400 cases of adulthood chickenpox infection
• •
  Cytomegalovirus (CMV)

  • ○
    CMV infection: > 70% of hematopoietic stem cell transplant (HSCT) recipients; ∼ 1/3 develop CMV pneumonia

    • –
      Infection during postengraftment period (30-100 days after transplantation)
• •
  Epstein-Barr virus (EBV)

  • ○
    Primary infection manifests as infectious mononucleosis
  • ○
    EBV pneumonia: Rare in immunocompetent or immunocompromised subjects
  • ○
    Associated with development of Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma

IMAGING

Radiographic Findings

• •
  Variable and overlapping appearance

  • ○
    Normal at presentation (20%)
• •
  Tracheobronchitis

  • ○
    Bronchial wall thickening
  • ○
    Atelectasis: Discoid to segmental (mucus plugs)
• •
  Pneumonia

  • ○
    Focal consolidation: Peripheral, mid, and lower lung zones (40%)
  • ○
    Unilateral or patchy bilateral areas of consolidation
  • ○
    Diffuse consolidation
• •
  Complications

  • ○
    Bacterial superinfection: Sudden worsening, cavitation, or enlarging pleural effusion
• •
  Uncommon findings

  • ○
    Hilar or mediastinal lymphadenopathy: Measles and infectious mononucleosis
  • ○
    Splenomegaly: Infectious mononucleosis
• •Cardiac enlargement (pericardial effusion): Hantavirus
• •
  Pleural effusion

  • ○
    Rare except for adenovirus, measles, hantavirus, HSV-1

CT Findings

• •
  Alterations of parenchymal attenuation

  • ○
    Patchy heterogeneous pulmonary attenuation (mosaic attenuation pattern)

    • –
      Bronchiolar obstruction (inflammation or cicatricial scarring) and secondary vasoconstriction

      • □
        Inspiratory/expiratory CT: Differentiation of bronchiolar from pulmonary vascular disease
      • □
        Bronchiolar disease (air-trapping): Decreased attenuation on inspiration, accentuated on expiration
      • □
        Vascular disease: Little increase in attenuation or decrease in volume
• •
  Ground-glass opacity and consolidation

  • ○
    Coexistence of interstitial thickening and partial airspace filling
  • ○
    Consolidation: Patchy and poorly defined (bronchopneumonia) vs. focal and well-defined (lobar pneumonia)
• •
  Nodules, micronodules, and tree-in-bud opacities

  • ○
    Nodules 1-10 mm in diameter common in viral infections

    • –
      Centrilobular nodules

      • □
        Inflammation, infiltration, or fibrosis of surrounding interstitium and alveoli
    • –
      Tree-in-bud opacities: Indicative of small airways disease

      • □
        Dilatation of centrilobular bronchioles with lumina impacted with mucus, fluid, or pus
    • –
      Branching or centrilobular nodules and mosaic perfusion: Common in viral bronchiolitis
    • –
      Miliary nodules

      • □
        Nearly any organism; typically tuberculosis, fungi, varicella-zoster virus
• •
  Interlobular septal thickening

  • ○
    Widespread with associated ARDS
• •
  Bronchial &/or bronchiolar wall thickening

  • ○
    Inflammatory exudates and bronchiolar wall thickening from edema and smooth muscle hyperplasia

DIFFERENTIAL DIAGNOSIS

Bacterial Pneumonia

• •Consolidation, cellular bronchiolitis
• •May exhibit cavitation

Aspiration

• •Basilar predominant cellular bronchiolitis
• •Esophageal abnormalities, neurological and deglutition disorders

Diffuse Alveolar Hemorrhage

• •Ground-glass opacities ± interlobular septal thickening (crazy-paving pattern)
• •No signs and symptoms of infection

Organizing Pneumonia

• •Peripheral or peribronchial consolidation
• •Migratory pulmonary opacities
• •Reversed halo sign

PATHOLOGY

Microscopic Features

• •Nodules contain infected cells with cytoplasmic inclusions: Cytomegalovirus, adenovirus, herpesvirus
• •Necrotizing bronchitis &/or bronchiolitis and diffuse alveolar damage (DAD): Influenza, RSV, parainfluenza viruses
• •Bronchiolitis and bronchiectasis: Adenovirus
• •Necrotizing bronchopneumonia, multicentric areas of hemorrhage (centered on airways): Herpes simplex virus
• •
  Acute interstitial pneumonia

  • ○
    Diffuse alveolar thickening by edema and mononuclear cells, airspace fibrinous exudate &/or hyaline membranes
  • ○
    CMV, hantaviruses (hantavirus pulmonary syndrome), SARS, and MERS
• •Endothelial damage to small vessels (focal hemorrhagic necrosis, mononuclear infiltration of alveolar walls, and alveolar fibrinous exudates): Varicella-zoster virus

CLINICAL ISSUES

Presentation

• •
  Most common signs/symptoms

  • ○
    Clinical syndromes

    • –
      Cold: Upper respiratory tract symptoms (tonsillopharyngitis, pharyngitis, epiglottitis, sinusitis, otitis media, and conjunctivitis)
    • –
      Influenza syndrome: Abrupt fever, headache, myalgias, and malaise
  • ○
    Acute bronchiolitis in infants and children: Wheezing with concomitant signs of respiratory viral infection

    • –
      RSV (most common), adenovirus, influenza, and parainfluenza
  • ○
    CAP: Cough, sputum, or dyspnea with fever or abnormalities at physical examination (rhonchi and rales)

    • –
      Influenza and RSV

      • □
        Comorbidities or risk factors: Smoking, COPD, asthma, diabetes mellitus, malignancy, heart failure, neurologic diseases, narcotic and alcohol use, and chronic liver disease
• •
  Clinical profile

  • ○
    Role of biomarkers

    • –
      Procalcitonin: ↓ with viral infection,↑ with bacterial infection,
  • ○
    Better quality of diagnostic tests have improved ability to detect multiple viruses

Demographics

• •Increasingly frequent cause of pulmonary disease worldwide
• •
  High rate of viral infection in CAP (2-35%)

  • ○
    Influenza, hMPV, and RSV: 2/3 of all viral pathogens in patients with CAP

Natural History & Prognosis

• •
  Variable prognosis

  • ○
    Complete resolution in immunocompetent individuals

DIAGNOSTIC CHECKLIST

Consider

• •Diagnosis relies on clinical suspicion: Host risk factors, presentation, and exposure history

Image Interpretation Pearls

• •Lobar consolidation uncommon in viral pneumonia
• •Nodules < 10 mm, may exhibit CT halo sign; do not exhibit cavitation
• •Branching or centrilobular nodules and mosaic perfusion/attenuation common in viral bronchiolitis

Coronal HRCT of a patient with acute infectious bronchiolitis secondary to respiratory syncytial virus (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 asthma in children.

Coronal HRCT of a 52-year-old woman with rhinovirus pneumonia shows multifocal ground-glass opacities bilaterally. Rhinoviruses are the predominant cause of the common cold but occasionally cause viral pneumonia.

Axial NECT of a 75-year-old man with herpes simplex virus 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.

Axial CECT of a 71-year-old woman with human metapneumovirus pneumonia shows bilateral consolidations and a small right pleural effusion . Human metapneumovirus is a common cause of viral pneumonia.

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.

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.

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.

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.

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.

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 diffuse alveolar damage. (Courtesy A.S. Sousa, MD.)

Axial CECT of a 34-year-old woman with influenza A pneumonia shows scattered bilateral peripheral ground-glass opacities and consolidations. The appearance is reminiscent of that of organizing pneumonia, which is often present in severe cases of viral pneumonia.

PA chest radiograph of a 68-year-old man with Middle East respiratory syndrome-Coronavirus (MERS-CoV) shows bilateral asymmetric patchy consolidations most pronounced in the right upper lobe.

Axial CECT of the same patient shows extensive right upper lobe ground-glass opacities with associated reticulation (crazy-paving pattern) and lobular consolidations This infection was initially reported in and near the Arabian Peninsula, but a large outbreak happened in Korea in 2015 associated with a traveler returning from the Arabian Peninsula.

Axial NECT minIP reformation of a patient with H1N1 virus infection shows ground-glass opacity with peripheral consolidation exhibiting the reversed halo sign consistent with organizing pneumonia, a pattern associated with H1N1 infection.

Coronal CECT of a patient with H1N1 pulmonary infection shows patchy areas of ground-glass opacity , bronchial wall thickening , and tree-in-bud opacities .

Axial CECT of a 51-year-old man who presented with dyspnea and fever shows multifocal lobular consolidations and tree-in-bud opacities without pleural effusion. Similar opacities were present in the right lung (not shown). The patient was diagnosed with parainfluenza virus pulmonary infection.