Viral infections account for 5% to 34% of community-acquired pneumonias.¹ Because many cases of community-acquired pneumonias are pathogenically undetermined, the rate of viral cause may be higher. With the onset of molecular testing, the frequency of viral detection in community-acquired pneumonia is almost one-third.² In addition, viral infections often precede bacterial pneumonias, and viruses and bacteria are both identified in patients with pneumonia in about 5% of cases.^3,4

Clinically, viral pneumonias are less likely to cause expectoration and cough than bacterial pneumonias, although there is no difference in the degree of fever.¹ Patients tend to be older and frailer and have a higher likelihood of cardiac disease.^4,5 There is no significant difference in the radiographic appearance of bacterial and viral pneumonias.¹

The most common organisms are influenza A and B, human parainfluenza virus, respiratory syncytial virus (RSV), and adenovirus.^1,6 With the use of expanded molecular panels, other viruses, such as metapneumovirus, coronavirus, and rhinovirus, have been implicated.^2,3,4

The pathologic findings of viral pneumonias in immunocompetent patients, which are usually self-limited, are not well studied, as pathologic sampling is not performed for diagnosis.

Nosocomial pneumonias in immunocompetent patients are usually bacterial,⁷ with the exception of cytomegalovirus (CMV) pneumonia. Nosocomial viral infections are however common in immunocompromised patients, especially in organ transplant patients, patients with chemotherapy-induced immunosuppression, and neutropenic patients with HIV/AIDS.

The most common viral pneumonia in immunocompromised patients is CMV pneumonia. Because of the high likelihood of reactivation of CMV, solid organ transplant patients are routinely given prophylaxis in the initial stages after transplant, either with ganciclovir or valganciclovir.^8,9,10,11 In open lung biopsies performed for unexplained lung opacities in immunocompromised patients, CMV is detected by light microscopy and immunohistochemistry in 3% to 6% of biopsies.^12,13,14

RSV also causes pneumonia in immunosuppressed patients, with a mortality rate between 10% and 20%.^15,16 A number of other viral pneumonias occur in the immunocompromised, including varicella, HSV, and metapneumoviruses.^17,18,19

The diagnosis of pneumonia is generally made in the microbiology laboratory, except in instances of open lung biopsy in immunocompromised patients, in which viral inclusions are identified by H&E, immunohistochemistry, or in situ hybridization. In addition to histology, cell culture techniques, serology, polymerase chain reaction (PCR), and electron microscopy are all important in diagnosing viral pneumonias.

Viruses require live cells for cultivation and are more difficult than bacteria to isolate from clinical samples. The traditional viral culture uses shell vials that take up to 5 days, are labor intensive, and suffer from a lack of sensitivity.

The least expensive method of diagnosing a viral cause of a patient with pneumonia is the detection of seroconversion for a specific viral antigen, with a fourfold rise in IgG titers.¹ This method requires a delay of weeks, however, and serial testing of the patient’s serum.

A more rapid test is the direct immunofluorescence assay performed on nasopharyngeal swabs for influenza virus types A and B, parainfluenza virus types 1 to 3, adenovirus, and RSV.^4,6

Nasopharyngeal samples can also be subjected to PCR and nucleotide amplification for pathogens such as influenza A and B, human metapneumovirus (HMPV), RSV, rhinovirus, parainfluenza 1 to 4, coronaviruses (OC43, 229E, and NL63), and adenoviruses.^2,4 Expanded molecular respiratory pathogen panels detect up to 20 pathogens, including 3 bacteria, with a turnaround time of hours.²⁰

Although not used routinely in the clinical setting, electron microscopy may be critical in outbreaks of unknown etiology, as it was in the Hendra virus, Nipah virus, and coronavirus outbreaks in 1994, 1999, and 2003, respectively.

Influenza accounts for 14% to 64% of viruses detected in patients hospitalized for pneumonia.^1,2,4,6 There are no particular clinical features that distinguish influenza from other viral pneumonias.⁴

Influenza virus belongs to the Orthomyxoviridae family of RNA viruses. Types A and B are associated with significant human disease. Influenza A viruses are further classified based on the antigenicity of their hemagglutinin and neuraminidase surface glycoproteins, of which there are 16 and 9 subtypes, respectively. Only subtypes HI, H2, and H3 and subtypes Nl and N2 have established stable lineages in the human population since 1918. There have been few human outbreaks of avian flu H5N1 (Ng), and an epidemic of a swine virus of the H1N1 subtype occurred in 2009.²¹

Reported pathologic findings are based largely on autopsies that are skewed toward fatal cases, which represent a small fraction of infections. For example, in the H1N1 outbreak, only 5% of cases were fatal in the southern Indian region of Hyderabad.²¹

Autopsied lungs are heavy, with subpleural hemorrhages. The mucosa of the trachea and bronchi are hemorrhagic and swollen, and the cut surfaces of the lungs show diffuse hemorrhagic consolidations.²¹ Bloody pleural effusions are common.²²

Inflammatory changes occur in both the airways and lung parenchyma. There is chronic inflammation in the walls of the bronchi and bronchioles, with acute bronchiolitis and necrosis of bronchiolar mucosa. The parenchyma shows diffuse alveolar damage with hyaline membranes, expansion of the alveolar septa by edema and chronic inflammation, and intra-alveolar edema and hemorrhage.²¹ No viral inclusions are identified (Table 39.1).

As is typical of alveolar injury of any cause, the diffuse alveolar damage associated with influenza pneumonia evolves through an acute exudative phase in the first 2 weeks and an organizing phase in patients dying in the 3rd week or later.²²

RSV is a member of the RNA virus family Paramyxoviridae. Of the two groups (A and B), the subgroup A strains are associated with more severe infections. RSV is the most common cause of bronchiolitis and pneumonia among infants and children under 1 year of age²³ and accounts for 7% to 10% of viral infections of the lower respiratory tract in immunocompetent adults.^1,2,4 In immunocompetent children, RSV pneumonia is rarely lethal (Table 39.2).^24,25