A virus must first gain access to the lower respiratory tract in order to produce severe pneumonia. The most common mode of entry is via droplet transmission. Airborne virus-containing droplets 5 to 10 μm in diameter are filtered and deposited in the upper respiratory tract. Virus reaches the lower respiratory tract after efficient replication and spread within squamous epithelial cells, often in the setting of impaired mucociliary clearance (due to extremes of age, antecedent or concurrent infections, and drugs). This is the usual mode of entry for many human-adapted respiratory viruses, such as influenza, RSV, adenovirus, and coronavirus. Person-to-person spread via droplets is limited to a distance of approximately 1 m. Other viruses such as varicella and rubeola are transmitted via aerosols (particles 1 to 5 μm in diameter) that can deposit directly in the lower respiratory tract. As such, they are highly infectious and can be transmitted over greater distances and time than agents transmitted by droplets. Although deposited directly in alveoli, viral dissemination in the lung typically occurs hematogenously after a viremic phase [1,2].

Once in the lower respiratory tract, there are a limited number of ways that the lung can respond to a viral infection and produce respiratory illness. Viral invasion and replication can directly produce a necrotizing bronchopneumonia with highly inflammatory, purulent, and exudative reactions. This is not common, but can be seen with influenza and adenovirus infections. Respiratory viral infections can impair host lung defenses in a way that leads to secondary bacterial pneumonias, particularly with Streptococcus pneumoniae or Staphylococcus aureus. The classic examples are postinfluenza or measles pneumonias. Finally, viral infection of the lower respiratory tract may produce severe disease by triggering a common tissue response to acute lung injuries termed diffuse alveolar damage or acute respiratory distress syndrome. The acute lung injury may progress from an early exudative phase, often with profound noncardiogenic pulmonary edema (especially in HCPS), to a proliferative or organizing phase that produces interstitial inflammation, and a late resolving phase [3].

The limited host response patterns to virus-induced lung injury means that there is significant overlap in the clinical manifestations of viral pneumonias. The clues to a specific viral etiology are often found in assessing host risk factors and epidemiology on presentation. A summary of the common clinical manifestations for specific viral pneumonias is presented in Table 90.1. Many of the viral infections discussed in this chapter are characterized by a “flu-like illness” prodrome. Symptoms begin with the acute onset of headache, chills, and myalgias. Within a few days, a cough and sore throat develop along with upper respiratory tract infection. The presence or absence of upper respiratory symptoms at this stage may provide one clue to the specific viral etiology. The human-adapted respiratory viruses (human influenza, RSV, adenovirus, non-SARS coronavirus) generally all produce upper respiratory symptoms. Measles is characterized by coryza and conjunctivitis in the prodrome. The absence of upper respiratory symptoms has been reported to be characteristic of infections with several of the zoonotic viruses: SARS coronavirus, hantavirus, and the H5N1 avian influenza virus [4,5,6]. The lower respiratory tract signs and symptoms in viral pneumonias are generally nonspecific and progress to dyspnea, tachypnea, and inspiratory crackles. Sputum production is variable. If the clinical course is biphasic (dyspnea and productive cough after improvement of a flu-like illness), then a secondary bacterial pneumonia should be suspected.

Routine laboratory tests are generally of little help in distinguishing among the viruses that can produce severe respiratory illness. Total leukocyte counts are typically within the normal range or slightly elevated. One exception is measles virus infection, which can produce a marked leukopenia [7]. The most common hematologic finding in the viral pneumonias is a relative lymphopenia. The complete blood count may be useful for diagnosing HCPS. In HCPS caused by Sin Nombre virus (a New World hantavirus), the triad of thrombocytopenia (platelet count less than 150 K per mm³), absolute neutrophilia, and the presence of immunoblasts was a sensitive and specific predictor of HCPS in one study [5]. Electrolyte abnormalities and hepatic transaminase elevation can occur among any of the severe viral pneumonias.

The radiographic findings in viral pneumonias are also broad and nonspecific. Radiographic infiltrates can have interstitial, alveolar, or combined patterns. The presence of only a diffuse alveolar pattern might suggest a primary influenza pneumonia with hemorrhagic alveolitis [8] or the capillary leak syndrome of acute respiratory distress syndrome, especially due to HCPS. Peribronchial nodular infiltrates is a pattern often reported with varicella pneumonia [9]. Computed tomography (CT) scans are better at detecting the presence, extent, and complications of respiratory infections than chest radiographs. However, they are no better at defining particular radiographic patterns of specific viral or bacterial causes [9].

The diagnostic modalities available for viral pneumonias rely on detection of a viral component (nucleic acid or protein), growth of the virus in vitro, or development of a virus-specific antibody response. Definitive serologic evidence of a viral infection requires a rise in virus-specific antibody titers between paired acute illness and convalescent sera. With a few exceptions, serologic assays are therefore not generally helpful for the clinician in the acute setting of a viral pneumonia. This section will focus on diagnostic tests that may assist the clinician faced with a critically ill patient and suspected viral pneumonia.