COMMENTARY

Commonly Encountered Respiratory Virus Infections: Update and New Treatments

Shmuel Shoham, MD; Megan K. Morales, MD

Disclosures

November 08, 2016

RSV: Not Just for Little Kids

Home from college and an emergency department visit. A 19-year-old college student home for winter break presents to the emergency department with increased wheezing, cough, dyspnea on exertion, and chest tightness. She also reports rhinorrhea and subjective fever. She has a rescue inhaler, which she started using with increased frequency during this illness, although she notes little relief. A chest radiograph shows increased markings in the bases but no focal consolidation or effusion. She has been working as a nanny while home for the past 2 weeks. In addition to supportive respiratory care, multiplex viral PCR is performed and returns 2 hours later positive for RSV.

Although RSV is best recognized as a childhood illness, it is also a major cause of illness in adults. In the Northern Hemisphere, RSV season typically lasts from November to April and peaks during winter. RSV usually causes a mild, self-limited illness in healthy adults.

The situation is different in elderly and immunocompromised patients. Every year in the United States, RSV accounts for an estimated 10,000 deaths in people older than 65 years, contributes to ~10% of hospitalizations for pneumonia and chronic obstructive pulmonary disease, and is associated with hospitalization costs exceeding $1 billion.[9,10] RSV can be particularly dangerous in highly immunocompromised patients, such as those with leukemia and bone marrow transplant (BMT), in whom respiratory failure and even death are not uncommon.[11,12]

Supportive care is sufficient for most patients. In asthmatic patients, corticosteroids are often used but lack clear benefit.[13,14] Specific anti-RSV therapy is used in very young children and highly immunocompromised patients (such as those with BMT or lung transplant).

Antivirals for RSV

Aerosolized ribavirin is approved by the US Food and Drug Administration (FDA) for treatment of infants and young children with severe infection.[15] It is also used off-label in BMT and lung transplant recipients for preventing RSV progression from upper to lower respiratory tract infection (LRTI) and for the treatment of established LRTI.

Aerosolized ribavirin is not a straightforward drug to use. It is teratogenic, requires special containment practices, and is very expensive. The package insert has a black-box warning against use in pregnant women and their male partners, and advises avoidance of pregnancy for 6 months after treatment.[14,16]

As of September 2015, the cost of inhaled ribavirin was approximately $150,000 for the 5-day course used for prevention of progression to LRTI and twice that for the 10-day LRTI course.[17] Although variability in prescribing patterns exists, clinicians are increasingly using oral ribavirin for highly immunocompromised patients with RSV, a practice that appears to be safe and cost-effective.[18,19] Side effects include hemolytic anemia or other cytopenias, fatigue, mood changes, and gastrointestinal upset.

GS-5806 (presatovir) is an investigational oral RSV-entry inhibitor.[20] In a double-blind, placebo-controlled study in healthy adults who received an intranasal challenge strain of RSV, use of GS-5806 resulted in significantly lower viral load, lower total mucus weight, and lower symptom scores. A review of ClinicialTrials.gov before publication of this article showed four actively recruiting phase 2b randomized, controlled trials on the use of GS-5806 in hospitalized adults, lung transplant recipients, and hematopoietic stem cell transplant recipients with RSV respiratory tract infection.

Immunotherapy

The monoclonal antibody palivizumab (Synagis®) is FDA-approved for the prevention of RSV in high-risk children. It is safe in adult BMT patients, but it has not been proven effective in preventing progression to LRTI or in improving survival.[21]

Motavizumab is a second-generation anti-RSV antibody that significantly reduces cultivatable RSV in the respiratory tract and has shown promising results in preventing RSV in infants.[22,23] At this time, however, it has yet to gain FDA approval.

RI-002, an intravenous immunoglobulin (IVIG) formulation containing high titers of anti-RSV neutralizing antibody, has been shown in animal studies to accelerate viral clearance and reduce damage to pulmonary tissue and airway lining.[24] In adult and pediatric patients with primary immunodeficiency, treatment with RI-002 resulted in increased anti-RSV neutralizing antibody titers by as much as 6.8-fold and no serious bacterial infections during the year-long study period.[25] RI-002 also has higher antibody titers to parainfluenza, influenza, coronavirus, and metapneumovirus than standard IVIG. Of note, an earlier RSV-intense IVIG formulation, RespiGam®, was voluntarily withdrawn from the market after the introduction of palivizumab.

No antibiotics needed. With the information that this college student has RSV infection, her clinician does not prescribe an antibiotic. Her symptoms ultimately resolve. On further questioning, it is discovered that the children for whom she had been caring had mild upper respiratory tract infections as well.

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