Over the past 2 decades, advances in stem cell transplantation procedures and improvements in the clinical management of hematopoietic cell transplant (HCT) recipients, including better strategies for the prevention and treatment of post-transplant complications such as opportunistic infections, have led to an increase in survival duration [1
]. HCT recipients are, however, still particularly susceptible to community respiratory viruses (CRVs) owing to a decreased host immune response, mainly because of a shortage of T cell lymphocytes [2
]. CRVs, including respiratory syncytial virus (RSV), influenza virus, parainfluenza virus (PIV), human adenovirus (HAdV), human metapneumovirus (HMPV), human rhinovirus (HRhV), and human coronavirus (HCoV), have been reported to cause infections in this population at incidences between 1% and 30%, as shown in [3
]. Other newly discovered viruses such as human bocavirus (HBoV) are emerging as potential causes of respiratory infections, but data on their impact in this population are lacking. All of these CRVs can potentially cause lower respiratory tract illnesses (LRTI) (rates of LRTI range from 5% to 50%), which could be associated with high mortality rates (10% to 50%) in HCT recipients [3
]. As demonstrated in , HAdV, HRhV, and HCoV have equally higher incidences in HCT recipients, whereas LRTI rates are higher for RSV, influenza, PIV, HAdV, and HMPV. Other late complications, such as bronchiolitis obliterans and organizing pneumonia, have been associated with some of these viral infections (i.e., RSV, PIV, and HMPV) [8
], but the direct relationship needs to be better elucidated.
Figure 1 Incidence of respiratory viral infections and associated LRTI and mortality in HSCT recipients. Data obtained from [3,5,6,21]. *CRV indicates common respiratory viral infections; HSCT, hematopoietic stem cell transplant; LRTI, lower respiratory tract (more ...)
HCT recipients with CRV infections may present with various combinations of upper respiratory tract infection (URTI) symptoms such as rhinorrhea, nasal or sinus congestion, cough, low-grade fever, headache, otitis media, wheezing, and sore throat. Some patients may present with LRTI, with symptoms including dyspnea and hypoxemia and radiologic findings that include new or changing bilateral interstitial infiltrates. These signs and symptoms are suggestive of viral etiology, but laboratory confirmation is needed for a definitive diagnosis. Viral culture is the gold standard for diagnosing CRVs, but the time required for a culture to become positive is a limiting factor, especially in immunocompromised patients, where prompt institution of treatment is of utmost importance [10
]. Direct immunofluorescence antigen testing is a rapid and inexpensive alternative, but it has low sensitivity (50% to 93%) [12
]. More sensitive and specific modalities include molecular assays (e.g., multiplex polymerase chain reaction [PCR]) that test for multiple different viruses [18
], and real-time PCR is becoming the most preferred method for diagnosing viral infections.
The management of CRV infections in HCT recipients includes supportive care and, when available, antiviral therapy, especially in individuals at high risk of developing LRTI. Some evidence of successful antiviral therapy has been reported with ribavirin for RSV, oseltamivir, zanamivir, and/or M2 inhibitors for influenza, and cidofovir for HAdV. There are also some anecdotal reports of PIV and HMPV infections being successfully treated with a combination of ribavirin and intravenous immunoglobulins (IVIGs). However, none of these regimens have been tested in randomized controlled trials to determine their efficacy in HCT recipients and, therefore, are not licensed by the US Food and Drug Administration (FDA) for virus-specific therapy in these patients.
With the high morbidity and mortality rates associated with CRV infections and the lack of directed antiviral therapy for most of these infections, prevention remains the mainstay for reducing their incidence and controlling transmission in HCT recipients. A licensed vaccine is only available for the influenza virus, and its use should be encouraged in all HCT recipients, when indicated, as well as in healthcare workers and family members. Infection control measures should be emphasized for healthcare workers and patients alike and should focus on basic precautions such as frequent hand washing and the use of protective equipment such as face masks, gowns, and gloves.
In this review, we discuss the available data behind the use of antiviral therapy, adjuvant therapy, and novel investigational drugs, as well as available means for prevention, in each respiratory virus with a significant incidence in HCT recipients.