Definitive diagnosis depends on laboratory confirmation. The most definitive test is isolation of the virus in cell culture media. RSV grows in HEp2 cells, HeLa cells, and cells adapted from type II human alveolar epithelial carcinoma cells, known as A549. Optimal specimens can be obtained by gentle aspiration of nasal or nasopharyngeal secretions or more commonly by nasal swabs. RSV can also be detected in macrophages recovered from BAL fluids or from epithelial cells of patients with a background of marrow, heart, lung, or renal transplants (Collins and Crowe 2002; Haselton 1996). In addition to viral isolation, the diagnosis can be established by direct detection of viral antigen in clinical specimens, using enzyme-linked immunoassay, immunofluorescence, immunohistochemistry, or detection of viral RNA by RT-PCR or by demonstration of a rise in RSV-specific serum antibodies. The virus is extremely labile and does not survive long, and attempts at culture isolation may fail if there is a delay in the submission of the clinical specimen to the laboratory (Zaki and Paddock 2008). Another diagnostic modality is ultrastructural analysis of the virion. An analysis showing pleomorphic features, size within recognized limits (see above), and numerous 12 nm glycoprotein spikes coupled with appropriate clinical and serological data can be regarded as consistent with RSV infection. In our laboratory we screen specimens with a solid-phase EIA, a test that has good specificity and a rapid (less than 1 h) turnaround time. In the event of a negative EIA result, we proceed with a more sensitive test such as direct immunofluorescence (DFA), viral culture, or molecular testing. The sensitivity of DFA is comparable to that of viral culture and, if positive, can be regarded as diagnostic.

Clinically, the differential diagnosis includes pneumonia caused by adenoviruses, rhinoviruses, enteroviruses, and influenza viruses as well as infections by Chlamydia trachomatis, particularly in infants younger than 4 months. In HIV-infected children, infection by Pneumocystis jiroveci should also be considered (Collins and Crowe 2002). Viral pneumonias other than RSV pneumonia can be manifested histopathologically as inflammatory processes containing large or giant multinucleated giant cells. These pneumonias include measles, parainfluenza, and varicella/herpes zoster pneumonias. Human metapneumovirus (MPV) produces changes comparable to RSV and should also be included in the differential diagnosis (Kradin and Mark 2010). A helpful hint is that children in pediatric ICUs infected with MPV are likely to be older than those with RSV infection and more likely to present with pneumonia rather than a bronchiolitis type of illness (Paget et al. 2011).

Patients with increased risk of severe or fatal infection include premature infants with congenital heart or lung disease and children with cystic fibrosis or severe immunodeficiency. See vaccination below.

Currently, there is no effective vaccine against RSV, but prophylaxis with neutralizing antibodies appears to reduce the need for hospitalization and to be the best method for preventing severe disease. Inhaled ribavirin is effective and has been approved for use in the management of hospitalized infants and young children with severe lower respiratory tract infections. The role of ribavirin in adults is less well documented, but some reports indicate favorable results in adults with RSV infections. An exception is RSV infection associated with clinical ARDS syndrome in previously healthy adults. In this setting, the mortality rate is very high, 40–60 % as reported by Luo et al. (2011). However, some of these patients may also respond to ribavirin with clinical improvement and restoration of pulmonary function to near normal levels, as reported by the same authors (Luo et al. 2011).