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 tract virus load, duration of virus shedding, select mucosal chemokine and cytokine levels, humoral and mucosal immunoglobulin responses, and systemic T-cell responses were measured.

Results: A total of 111 RSV-infected adults (61 outpatients and 50 hospitalized patients) were evaluated. Hospitalized subjects shed virus in nasal secretions at higher titers and for longer durations than less ill outpatients, had greater mucosal interleukin 6 (IL-6) levels throughout infection, and had higher macrophage inflammatory protein 1α (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 level, and longer duration of virus shedding were associated with severe disease. Older age and increased nasal MIP-1α levels were of borderline statistical significance.

Conclusions: Multiple factors, but not older age, are independently associated with severe RSV infection in adults. The presence of underlying medical conditions had the greatest influence on disease severity.

Figure 1.

Kinetics of serum microneutralization titer to group A respiratory syncytial virus (RSV; MNA) in RSV-infected outpatients with mild disease. Down arrow indicates mean time of evaluation for the outpatient group, and up arrow indicates mean time of evaluation for the hospitalized group.

Figure 2.

Relationship between nasal respiratory syncytial virus (RSV)–specific immunoglobulin A (IgA) and viral titers in subjects ill for ≤4 days at the time of evaluation. A, IgA to F: r = −.22, P = .07. B, IgA to Ga: r = −.44, P = .0002. C, IgA to Gb: r = −.40, P = .001.

Figure 3.

CD8⁺ T-cell responses during acute respiratory syncytial virus (RSV) infection (4 groups): healthy controls (n = 5), persons <40 years of age with mild disease (young mild; n = 10), persons ≥65 years of age with mild disease (old mild; n = 13), and older persons with severe disease (old severe; n = 10). A, The top panel shows CD8⁺Ki-67⁺Bcl-2⁺ CD8⁺ T cells (ie, proliferating CD8⁺ T cells), and the bottom panel shows CD8⁺CD38⁺HLA-DR⁺ CD8⁺ T cells (ie, activated CD8⁺ T cells). B, Mean percentages (±SD) of CD8⁺ T cells that were Ki-67⁺Bcl-2⁺ (left) or CD38⁺HLA-DR⁺ (right) from each group. The mean time of blood collection (±SD) in relation to symptom onset was similar for each group (mild young, 4.8 ± 1.8 days; mild old, 5.5 ± 1.4 days; and severe old, 5.9 ± 2.1 days). All times were expected to coincide with peak viral shedding.