Influenza is a rod-shaped RNA virus that can cause either bronchiolitis or DAD without cytopathic changes. Influenza infection recurs each year due to a high incidence of mutation of its hemagglutinin (H) and neuraminidase (N) antigens, and these determine its virulence. When mutations occur concomitantly in both the H and N antigens, pandemics with potentially high degrees of morbidity due to the lack of immunity may ensue. Currently, epidemiologists are carefully monitoring the evolution of an avian influenza in southeast Asia for evidence of spread to man.
Influenza is the most common cause of viral pneumonia, although most cases are subclinical. The virus most commonly causes a diffuse tracheobronchitis/bronchiolitis in which the normal ciliated respiratory epithelium is sloughed. But when DAD develops, it carries a high mortality even in the absence of acute bacterial superinfection. The lungs in DAD due to influenza of patients with prolonged survival often develop prominent squamous metaplasia of bronchialalveolar lining cells. Although these findings are characteristic, they are also nonspecific, so that immunostains, in situ hybridization, electron microscopy, or viral antigen detection, may be required to establish the diagnosis. Superinfection by pyogenic bacteria, including H. influenza, Group A Streptococcus, and Staphylococcus, is a well-recognized complication and may mask evidence of a healing influenza infection.
Serious Acute Respiratory Syndrome
The recent epidemic of the zoonotic coronavirus infection termed serious acute respiratory syndrome (SARS) fortunately has not recurred, as the virus led to acute respiratory distress with high mortality. The lungs at autopsy showed DAD with scattered multinucleated giant cells of uncertain diagnostic significance. Otherwise, the virus otherwise produced no cytopathic changes and was essentially histologically indistinguishable from DAD due to influenza.
Middle Eastern Respiratory Syndrome
Like SARS, middle eastern respiratory syndrome (MERS) is caused by a coronavirus. The first cases were reported in Saudi Arabia in the fall of 2012, but the first recognized cases occurred in Jordan earlier that year. All cases of MERS to date have been linked through travel to or residence in countries in and near the Arabian Peninsula. The largest known outbreak of MERS outside the Arabian Peninsula occurred in the Republic of Korea in 2015 and was associated with a traveler returning from the Arabian Peninsula. MERS-CoV spreads from ill people to others via close contact, such as caring for or living with an infected person, and patients have ranged in age from infants to nonagenarians.
Patients present with fever, cough, and dyspnea. Almost 75% of reported patients with MERS have died and most have had an underlying medical condition. Some infected people have had mild symptoms of a upper respiratory infection (URI) or even no symptoms at all, and they all recovered. Incubation time ranges from 2 days to 2 weeks. Diagnosis is confirmed by RT-PCR at the Center for Disease Control for the implicated coronavirus. The pathology of the disorder has not been established but radiographically the pictures appear to be that of a severe organizing pneumonia.
Respiratory Syncytial Virus
Respiratory syncytial virus (RSV) causes a benign respiratory infection in older children and has been recognized as a cause of adult community-acquired pneumonia, acute bronchiolitis, and DAD in the immunosuppressed host. The infection targets the respiratory lining epithelium producing syncytial giant cells with nonprominent eosinophilic inclusions. Human metapneumovirus produces changes comparable to respiratory syncytial virus (RSV) and must be included in its differential diagnosis.
Parainfluenza causes a benign URI in children that rarely progresses to DAD, although severe disease may develop in the immunosuppressed host. Like RSV, parainfluenza produces bronchiolitis and DAD with syncytial giant cells and epithelial
cell intracytoplasmic inclusions. However, the latter are both more frequent and larger than those seen in RSV.
Measles pneumonia is a rare and serious complication of the childhood viral exanthem. The pathology of pulmonary measles infection ranges from bronchiolitis to DAD. The virus produces multikaryons with prominent glassy eosinophilic nuclear Cowdry type A inclusions. The differential diagnosis of giant cell pneumonia includes
RSV and hard-metal pneumoconiosis; however, the giant cells in the latter disorders lack intranuclear inclusions and the giant cells in hard-metal pneumoconiosis specifically lack the exudative features of an acute infection.