RSV Infection After Lung Transplantation


By Ramsey Hachem, M.D.

Washington University School of Medicine Barnes-Jewish Hospital
Division of Pulmonary and Critical Care

October, 2010

Respiratory syncytial virus (RSV), a single-stranded RNA virus, is a member of the paramyxovirus family which includes measles, mumps, and parainfluenza.  RSV causes an acute respiratory illness in people of all ages, and most have been infected at least once by the age of 3 years, but re-infection is common even in a single season.  RSV infection is seasonal, typically occurring between December and March in the northern hemisphere.  The virus is transmitted from person to person directly and can survive on the hands for several hours, underscoring the importance of hand washing to prevent transmission.  The severity of the illness depends on the patient’s underlying health.  It is one of the most common respiratory infections in children under the age of 1 year, and causes a severe infection in premature infants and children with congenital heart defects or chronic lung disease.  In healthy adults, RSV typically causes a self-limited upper respiratory tract infection and serious disease is unusual.  However, RSV can cause a severe illness in immunosuppressed adults and those with underlying lung disease.

Typical symptoms of RSV infection include sinus congestion, cough, and wheezing.  Fever is typically only low-grade, unlike the high-grade fever characteristic of influenza.  Gastrointestinal symptoms, such as nausea, vomiting, and diarrhea are uncommon.  However, severe pneumonia can develop in immunocompromised adults.  Pneumonia with respiratory failure is a common complication of RSV infection among stem cell transplant recipients, but this is unusual among lung and other solid organ transplant recipients.  Nevertheless, because the virus typically infects the lower respiratory tract in lung transplant recipients, it causes inflammation and edema of the small airways.  In addition, RSV infection can predispose to secondary bacterial respiratory infections in lung transplant recipients, and this usually complicates the illness further.  The diagnosis is usually made or confirmed by testing respiratory secretions, obtained by nasopharyngeal swab or wash, for viral antigens or RNA using various commercially available rapid assays.

Supportive and symptomatic care is typically the cornerstone of treatment for otherwise healthy adults.  Few drugs are currently available for the treatment of RSV infection, and these can only be recommended for infants at high risk for severe infection or immunosuppressed adults.  Ribavirin is an antiviral drug that is used for the treatment of hepatitis C and RSV.  For RSV, it is typically aerosolized but the oral and intravenous routes have also been used.  It does have some side effects including anemia, bronchospasm, and birth defects in pregnant women, but it is generally well tolerated.  Nevertheless, its routine use in otherwise healthy adults or children is not recommended because studies demonstrating efficacy have been lacking.  On the other hand, cases series in stem cell and lung recipients have shown some benefit, but it is important to note that the efficacy of any treatment is difficult to determine in non-randomized studies.  Nevertheless, many transplant centers use ribavirin for the treatment of RSV infected patients.  Palivizumab is a monoclonal antibody to a highly conserved viral protein and is usually used to prevent infection in high-risk infants.  However, it has been used in severely ill immunocompromised patients, although this has not been well studied.  Lastly, bronchodilators and steroids are often used to alleviate the bronchiolitis symptoms of coughing and wheezing.

For most healthy children and adults, there are no long-term sequelae of RSV infection.  However, some children are more likely to develop asthma and recurrent respiratory infections years after the RSV infection.  Furthermore, RSV infection increases the risk of bronchiolitis obliterans syndrome (BOS), or chronic rejection, after lung transplantation.  This is not unique to RSV as all respiratory viruses have this effect.  The exact mechanism is uncertain, but it is thought that viral infection of small airways in the lower respiratory tract triggers an inflammatory cascade that ultimately results in the small airway obliteration characteristic of BOS.

A new drug for RSV, ALN-RSV01, is currently being evaluated in a Phase 2 multi-center clinical trial.  The results of a small clinical trial using ALN-RSV01 in lung transplant recipients infected with RSV were recently published.  The drug reduced symptom scores, and more importantly, reduced the incidence of BOS 90 days after the infection.  The Phase 2 clinical trial aims to corroborate those findings in a larger cohort and is planning to enroll patients this season.  Obviously, this would be an important breakthrough in the management of the acute infection and the long-term sequelae in lung transplant recipients.