Dataset Information

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 1? (MIP-1?) 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-1? 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.

SUBMITTER: Walsh EE

PROVIDER: S-EPMC3610422 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Publications

Viral shedding and immune responses to respiratory syncytial virus infection in older adults.

Walsh Edward E EE Peterson Derick R DR Kalkanoglu Aja E AE Lee Frances Eun-Hyung FE Falsey Ann R AR

The Journal of infectious diseases 20130204 9

<h4>Background</h4>Comprehensive analyses of host, viral, and immune factors associated with severe respiratory syncytial virus (RSV) infection in adults have not been performed.<h4>Methods</h4>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.< ...[more]

PMID: 23382572

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Project description:IntroductionRespiratory syncytial virus (RSV) is an important cause of severe respiratory illness in older adults and adults with respiratory or cardiovascular comorbidities. Published estimates of its incidence and prevalence in adult groups vary widely. This article reviews the potential limitations affecting RSV epidemiology studies and suggests points to consider when evaluating or designing them.MethodsStudies reporting the incidence or prevalence of RSV infection in adults in high-income Western countries from 2000 onwards were identified via a rapid literature review. Author-reported limitations were recorded, together with presence of other potential limitations. Data were synthesized narratively, with a focus on factors affecting incidence estimates for symptomatic infection in older adults.ResultsA total of 71 studies met the inclusion criteria, most in populations with medically attended acute respiratory illness (ARI). Only a minority used case definitions and sampling periods tailored specifically to RSV; many used influenza-based or other criteria that are likely to result in RSV cases being missed. The great majority relied solely on polymerase chain reaction (PCR) testing of upper respiratory tract samples, which is likely to miss RSV cases compared with dual site sampling and/or addition of serology. Other common limitations were studying a single season, which has potential for bias due to seasonal variability; failure to stratify results by age, which underestimates the burden of severe disease in older adults; limited generalizability beyond a limited study setting; and absence of measures of uncertainty in the reporting of results.ConclusionsA significant proportion of studies are likely to underestimate the incidence of RSV infection in older adults, although the effect size is unclear and there is also potential for overestimation. Well-designed studies, together with increased testing for RSV in patients with ARI in clinical practice, are required to accurately capture both the burden of RSV and the potential public health impact of vaccines.

Project description:Respiratory syncytial virus (RSV) is increasingly recognized for causing severe morbidity and mortality in older adults, but there are few studies on the RSV-induced immune response in this population. Information on the immunological processes at play during RSV infection in specific risk groups is essential for the rational and targeted design of novel vaccines and therapeutics. Here, we assessed the antibody and local cytokine response to RSV infection in community-dwelling older adults (≥60 years of age). During three winters, serum and nasopharyngeal swab samples were collected from study participants during acute respiratory infection and recovery. RSV IgG enzyme-linked immunosorbent assays (ELISA) and virus neutralization assays were performed on serum samples from RSV-infected individuals (n = 41) and controls (n = 563 and n = 197, respectively). Nasal RSV IgA and cytokine concentrations were determined using multiplex immunoassays in a subset of participants. An in vitro model of differentiated primary bronchial epithelial cells was used to assess RSV-induced cytokine responses over time. A statistically significant increase in serum neutralization titers and IgG concentrations was observed in RSV-infected participants compared to controls. During acute RSV infection, a statistically significant local upregulation of beta interferon (IFN-β), IFN-λ1, IFN-γ, interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), IL-6, IL-10, CXCL8, and CXCL10 was found. IFN-β, IFN-λ1, CXCL8, and CXCL10 were also upregulated in the epithelial model upon RSV infection. In conclusion, this study provides novel insights into the basic immune response to RSV infection in an important and understudied risk population, providing leads for future studies that are essential for the prevention and treatment of severe RSV disease in older adults.IMPORTANCE Respiratory syncytial virus (RSV) can cause severe morbidity and mortality in certain risk groups, especially infants and older adults. Currently no (prophylactic) treatment is available, except for a partially effective yet highly expensive monoclonal antibody. RSV therefore remains a major public health concern. To allow targeted development of novel vaccines and therapeutics, it is of great importance to understand the immunological mechanisms that underlie (protection from) severe disease in specific risk populations. Since most RSV-related studies focus on infants, there are only very limited data available concerning the response to RSV in the elderly population. Therefore, in this study, RSV-induced antibody responses and local cytokine secretion were assessed in community-dwelling older adults. These data provide novel insights that will benefit ongoing efforts to design safe and effective prevention and treatment strategies for RSV in an understudied risk group.

Project description:ImportanceLittle is known about the burden and outcomes of respiratory syncytial virus (RSV)-positive acute respiratory infection (ARI) in community-dwelling older adults.ObjectiveTo assess the incidence of RSV-positive ARI before and during the COVID-19 pandemic, and to assess outcomes for RSV-positive ARI in older adults.Design, setting, and participantsThis was a community-based cohort study of adults residing in southeast Minnesota that followed up with 2325 adults aged 50 years or older for 2 RSV seasons (2019-2021) to assess the incidence of RSV-positive ARI. The study assessed outcomes at 2 to 4 weeks, 6 to 7 months, and 12 to 13 months after RSV-positive ARI.ExposureRSV-positive and -negative ARI.Main outcomes and measuresRSV status was the main study outcome. Incidence and attack rates of RSV-positive ARI were calculated during each RSV season, including before (October 2019 to April 2020) and during (October 2020 to April 2021) COVID-19 pandemic, and further calculated during non-RSV season (May to September 2021) for assessing impact of COVID-19. The self-reported quality of life (QOL) by Short-Form Health Survey-36 (SF-36) and physical functional measures (eg, 6-minute walk and spirometry) at each time point was assessed.ResultsIn this study of 2325 participants, the median (range) age of study participants was 67 (50-98) years, 1380 (59%) were female, and 2240 (96%) were non-Hispanic White individuals. The prepandemic incidence rate of RSV-positive ARI was 48.6 (95% CI, 36.9-62.9) per 1000 person-years with a 2.50% (95% CI, 1.90%-3.21%) attack rate. No RSV-positive ARI case was identified during the COVID-19 pandemic RSV season. Incidence of 10.2 (95% CI, 4.1-21.1) per 1000 person-years and attack rate of 0.42%; (95% CI, 0.17%-0.86%) were observed during the summer of 2021. Based on prepandemic RSV season results, participants with RSV-positive ARI (vs matched RSV-negative ARI) reported significantly lower QOL adjusted mean difference (limitations due to physical health, -16.7 [95% CI, -31.8 to -1.8]; fatigue, -8.4 [95% CI, -14.3 to -2.4]; and difficulty in social functioning, -11.9 [95% CI, -19.8 to -4.0] within 2 to 4 weeks after RSV-positive ARI [ie, short-term outcome]). Compared with participants with RSV-negative ARI, those with RSV-positive ARI also had lower QOL (fatigue: -4.0 [95% CI, -8.5 to -1.3]; difficulty in social functioning, -5.8 [95% CI, -10.3 to -1.3]; and limitation due to emotional problem, -7.0 [95% CI, -12.7 to -1.3] at 6 to 7 months after RSV-positive ARI [intermediate-term outcome]; fatigue, -4.4 [95% CI, -7.3 to -1.5]; difficulty in social functioning, -5.2 [95% CI, -8.7 to -1.7] and limitation due to emotional problem, -5.7 [95% CI, -10.7 to -0.6] at 12-13 months after RSV-positive ARI [ie, long-term outcomes]) independent of age, sex, race and/or ethnicity, socioeconomic status, and high-risk comorbidities.Conclusions and relevanceIn this cohort study, the burden of RSV-positive ARI in older adults during the pre-COVID-19 period was substantial. After a reduction of RSV-positive ARI incidence from October 2020 to April 2021, RSV-positive ARI re-emerged during the summer of 2021. RSV-positive ARI was associated with significant long-term lower QOL beyond the short-term lower QOL in older adults.

Dataset Information

Viral shedding and immune responses to respiratory syncytial virus infection in older adults.

Background

Methods

Results

Conclusions

Publications

Viral shedding and immune responses to respiratory syncytial virus infection in older adults.

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