Although respiratory syncytial virus (RSV) is primarily known for its high burden of disease in infants and young children, it is increasingly recognized as an important cause of severe respiratory disease in adults and individuals with comorbidities. In recent years, its impact on immunocompromised patients, particularly hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients, has also been recognized.
In older adults, RSV can lead to exacerbation of underlying lung and heart disease. It is also associated with significant morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients and may be associated with acute rejection and chronic pulmonary dysfunction in lung transplant recipients (LTRs). Dr. Daphne-Dominique H. Villanueva from West Virginia University, USA, and colleagues conducted a literature review and provided a comprehensive overview of RSV disease in older adults and in HSCT and SOT recipients [1].
The RSV pathogen spreads easily via droplets. It can also spread through direct contact with an infected person or by touching a contaminated surface. The incubation period is usually 2-8 days, while infected persons can remain contagious for 3-7 days, including one day before the onset of clinical symptoms. In the United States and other temperate regions of the Northern Hemisphere, the seasonal epidemiology of RSV is similar to that of influenza, with the highest incidence occurring in the fall, winter and spring. However, due to preventive measures against the 2019 coronavirus pandemic, cases of viral respiratory infections, including influenza, were at historically low levels in 2020. In the off-season, there was an increase in activity for some respiratory viral infections, including RSV. In the US, the spread of RSV has been reported since April 2021, with a sharp increase in the summer.
In Latin America, different RSV seasons have been reported depending on the geographical region, due to topographical differences in the region. Chile, for example, reported an RSV season from April to September, which coincides with fall and winter in the southern hemisphere, while in Mexico it reportedly lasted from August to March. The RSV season in Brazil varies by area – in regions closer to the equator, the RSV season usually coincides with the rainy and winter seasons, while in southeastern Brazil it usually occurs in the fall and winter.
The RSV diagnostic armamentarium includes rapid antigen detection tests (RADT), molecular diagnostics including reverse transcriptase polymerase chain reaction (RT-PCR), viral culture and serology. Although the sensitivity of RADT in pediatric patients can range from 78-85%, the test is significantly less sensitive in adults, with a pooled sensitivity of only 29% (range 11-48%). This is attributed to immunity due to previous RSV infection in adults, which in turn leads to lower viral titers in respiratory secretions and a shorter duration of viral shedding. According to Dr. Villanueva et al. it is therefore logical to resort to molecular diagnostic procedures when severe RSV disease is suspected in older adults.
While most infected adults have mild upper respiratory tract disease, some are at risk of severe RSV disease. These include people over the age of 65, people with chronic lung or heart disease and immunocompromised individuals, including SOT and HSCT recipients. Severe disease can lead to hospitalization, ventilator support and adverse outcomes, including death.
RSV in immunocompromised patients can have serious consequences
Previous observational studies have shown that RSV is the most commonly identified viral respiratory illness ( RVI) in HSCT and SOT recipients. In more recent studies, however, the incidence was lower. In a study of 1303 immunocompromised individuals with respiratory disease, routine bronchoalveolar lavage (BAL) fluid testing and multiplex polymerase chain reaction (PCR) for 20 viruses was performed. Viral infection was detected in about 35%. Of these, RSV was the fourth most common RVI identified, accounting for 8.2% of cases.
The infection is usually transmitted by droplet infection, but hospital transmission is also common, with many outbreaks documented in transplant departments. In addition to the seasonal epidemiology of RSV, the time since transplantation also plays an important role, as the clinical course of RSV tends to be more aggressive in the early postoperative period when patients are receiving the most intensive immunosuppressive therapies.
Diagnostics are largely based on nucleic acid tests due to their improved sensitivity, specificity and faster turnaround time. In addition, molecular techniques can be used to test multiple viruses simultaneously from a single sample. It is also important to consider the origin of the sample, the authors emphasize. In immunocompromised patients with pneumonia, the virus may not be present in nasopharyngeal specimens (NPS), and a sample from the lower respiratory tract is recommended in cases of diagnostic uncertainty. Rapid antigen detection is also available for RSV but has suboptimal sensitivity and low predictive value.
RSV is a common cause of self-limiting upper respiratory tract infections (URTI) in immunocompetent hosts, but HSCT and SOT recipients have a prolonged duration of illness caused by prolonged viral shedding over weeks or months. Immunocompromised hosts also tend to develop more severe disease with pneumonia associated with higher morbidity and mortality compared to other RVIs.
In a 10-year retrospective cohort study of 239 immunocompromised patients, 15.1% had bacterial coinfection, of whom 80.6% had bacteremia and 19.4% had bacterial pneumonia documented by BAL. According to the authors, bacterial coinfections increase the risk of progression to lower respiratory tract infection (LRTI), likely as a result of RSV-induced injury to the respiratory epithelium, which increases bacterial adherence. Up to half of HSCT or SOT recipients with RSV develop LRTI and have high RSV-associated mortality rates of up to 80%, Dr. Villanueva and colleagues report.
Prolonged virus excretion in immunocompromised patients
Earlier observational studies found a cumulative incidence of 0.4% to 1.5% in autologous HSCT and 3.5% to 9% in allogeneic HSCT recipients. However, more recent reviews using modern molecular diagnostic tests report an incidence of up to 12% in HSCT patients.
In the general population, RSV is known to be acquired in an outpatient setting, but nosocomial transmission is frequently reported in HSCT recipients and may account for approximately 50% of all cases. In an outbreak of RSV infection among HSCT recipients, patients in the pre-transplant phase or up to one month post-transplant had a higher risk of contracting RSV than transplanted patients. In addition, pre-transplant patients also tend to have higher rates of complications related to pneumonia and death. LRTI develops in about two-thirds of patients and is frequently observed in patients with an allogeneic stem cell transplant, a non-matching donor transplant, a graft-versus-host reaction (GvHR), advanced age, myeloablative therapy and a long duration of lymphopenia.
The results suggest that prolonged viral shedding is common in immunocompromised patients. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation and was most pronounced in patients with RSV infection with a median time to viral shedding of 80 days (range 35-334 days).
Recipients of lung transplants particularly susceptible to RSV complications
Lung transplant recipients (LTR) are the most studied population among adult organ transplant recipients because they are at increased risk for RSV-related morbidity and mortality compared to recipients of other organ transplants. Lung transplant recipients may initially show only shortness of breath or minor changes in lung function tests, without typical signs of severe RSV disease.
RSV occurs in adult lung transplant patients in about 6-16% of cases and develops into LRTI in about 40% of patients. Although mortality in lung transplant patients is lower than in HSCT recipients, morbidity remains high and mortality is between 10% and 20%. According to one study, 72% of lung transplant patients with RSV infections developed graft dysfunction. In terms of long-term outcomes, RSV-induced LRTIs have been associated with bronchiolitis obliterans syndrome (BOS). These affect the quality of life of transplant recipients. RSV in other SOT recipients also leads to significant morbidity but generally has a low mortality rate. However, studies on RSV in patients who have not received a lung transplant are limited, according to Dr. Villanueva’s research group.
Active prophylaxis and prevention of crucial importance
RSV infection leads to increased morbidity and mortality in immunocompromised patients. Given the significant impact of this common infection on at-risk patients, effective prevention strategies are crucial to protect this vulnerable population, the authors conclude. Furthermore, the significant spread of nosocomial infections in transplant wards highlighted in their study underlines the importance of infection prevention and control to prevent outbreaks.
Literature:
- Villanueva DDH, et al: Review of respiratory syncytial virus infection among older adults and transplant recipients. Therapeutic Advances in Infectious Disease 2022; 9; doi: 10.1177/20499361221091413.
InFo ONCOLOGY & HEMATOLOGY 2024; 12(5): 30-31
