Viral Shedding and Immune Responses to Respiratory Syncytial Virus Infection in Older Adults.
ABSTRACT Background. Comprehensive analyses of host, viral and immune factors associated with severe Respiratory Syncytial Virus (RSV) infection in adults have not been performed.Methods. Adults with RSV infection identified in both outpatient and inpatient settings were evaluated. Upper and lower respiratory viral load and duration of shedding, selected mucosal chemokine and cytokine levels, humoral and mucosal immunoglobulin responses, and systemic T cell responses were measured.Results. 111 RSV infected adults (61 outpatients, 50 hospitalized) were evaluated. Hospitalized subjects shed virus in nasal secretions at higher titers and longer than less ill outpatients, had greater mucosal interleukin (IL)-6 levels throughout infection, and higher MIP-1α levels early in infection. Persons >64 years old and those with more severe disease had a higher frequency of activated T cells in the blood than younger less ill subjects at infection. Multivariate analysis found that the presence of underlying medical conditions, female sex, increased mucosal IL-6, and longer duration of virus shedding were associated with severe disease. Older age and increased nasal MIP-1α levels were of borderline significance.Conclusion. Multiple factors, but not older age, are independently associated with severe RSV in adults. The presence of underlying medical conditions had the greatest influence on disease severity.
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ABSTRACT: Respiratory syncytial virus (RSV) is the most important cause of infantile bronchiolitis and a major pathogen in elderly and immunosuppressed persons. Although RSV shows limited antigenic diversity, repeated infections occur throughout life. Vaccine development has been delayed by poor immunogenicity, production issues and the fear of causing enhanced disease. T cells assist in viral clearance, but immune regulation serves to limit these responses and to prevent the exaggerated inflammatory response to RSV infection seen in children with bronchiolitis. Severe RSV disease can therefore be regarded as a dysregulated response to an otherwise trivial infection. Further insights into the role of T cells (including Th17) are needed to enable the rational design of safe, effective vaccines and novel treatments.06/2013; 3(4). DOI:10.1016/j.coviro.2013.05.005
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ABSTRACT: Background. Better understanding on complications and outcomes of adults hospitalized with RSV infection is necessary. Methods. A retrospective cohort study was conducted on all adults (≥18 years) admitted to three acute general hospitals in Hong Kong with virologically-confirmed RSV infection during 2009-2011 (n=607). Adults hospitalized for seasonal influenza during the period were used for comparison (n=547). Both infections were prospectively diagnosed following a standard protocol. Independent reviews of chest-radiographs were performed by radiologists. Main outcome measures were all-cause death, respiratory failure requiring ventilatory support and hospitalization duration. Cox proportional hazards models were used for analyses. Findings. The mean±S.D. age of RSV patients was 75±16 years; 87% had underlying conditions. Lower respiratory and cardiovascular complications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; COPD/asthma exacerbation, 27.3%) and 14.3% respectively; 12.5% had bacterial superinfections. Supplemental oxygen and ventilatory support was required in 67.9% and 11.1%, respectively. Crude all-cause mortality was 9.1% and 11.9% within 30 days and 60 days respectively; mean±S.D length-of-stay of survivors was 12±13 days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superinfection, elevated urea and WBC were independently associated with poorer survival. Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall outcomes of survival and length-of-stay were not significantly different from influenza. Interpretation. RSV can cause severe lower respiratory complications in the older adults, resulting in respiratory failure, prolonged hospitalization and high mortality similar to seasonal influenza. Corticosteroids did not seem to improve outcomes. The unmet need for antiviral therapy and vaccination against RSV in adults should be promptly addressed.Clinical Infectious Diseases 07/2013; 57(8). DOI:10.1093/cid/cit471 · 9.42 Impact Factor
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ABSTRACT: Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections in infants and children under the age of 5. Studies examining RSV infection in susceptible BALB/c mice indicate that both CD4 and CD8 T cells not only contribute to viral clearance but also facilitate RSV-induced disease. However, efforts to understand the mechanisms by which RSV-specific T cells mediate disease following acute RSV-infection have been hampered by the lack of defined RSV-specific T cell epitopes. Using an overlapping peptide library spanning each of the RSV-derived proteins, intracellular cytokine staining for interferon-γ was utilized to identify novel RSV-specific CD4 and CD8 T cell epitopes. Five novel CD8 T cell epitopes were revealed within the RSV fusion (F) protein and glycoprotein (G). In addition, five previously unidentified CD4 T cell epitopes were discovered including epitopes in the phosphoprotein (P), polymerase protein (L), M2-1 protein and nucleoprotein (N). Though the initial CD4 T cell epitopes were 15 amino acids in length, synthesis of longer peptides increased the frequency of responding CD4 T cells. Our results indicate that CD4 T cell epitopes that are 17 amino acids in length result in more optimal CD4 T cell stimulation than the commonly used 15-mer peptides.Journal of Virology 12/2013; DOI:10.1128/JVI.02139-13 · 4.65 Impact Factor