RSV Vaccine Effectiveness Against Hospitalization Among US Adults Aged 60 Years or Older During 2 Seasons

Abstract

Importance: Respiratory syncytial virus (RSV) vaccines for adults aged 60 years or older became available in 2023. One dose is recommended for all adults aged 75 years or older and those aged 60 to 74 years at increased risk of severe RSV; however, duration of protection is unknown.

Objective: To evaluate RSV vaccine effectiveness against RSV-associated hospitalization among adults aged 60 years or older during 2 RSV seasons.

Design, setting, and participants: A total of 6958 adults aged 60 years or older were included in this test-negative, case-control study if they were hospitalized with acute respiratory illness at any of 26 hospitals in 20 US states during the October 1, 2023, to March 31, 2024, or October 1, 2024, to April 30, 2025, RSV seasons and had respiratory virus testing within 10 days of illness onset. Case patients tested positive for RSV only; control patients tested negative for RSV, SARS-CoV-2, and influenza. Demographic and clinical data were obtained through patient interview and electronic health records.

Exposures: Receipt of 1 RSV vaccine dose at least 14 days before illness onset.

Main outcomes and measures: Multivariable logistic regression was used to compare the odds of RSV vaccination among hospitalized cases and controls. Models were adjusted for age, sex, race and ethnicity, geographic region, and calendar month and year. Vaccine effectiveness was estimated as (1 - adjusted odds ratio) × 100%. Analyses were stratified by timing of RSV vaccine receipt (same vs prior season) relative to illness onset.

Results: Of 6958 adults aged 60 years or older, 821 (11.8%) were RSV cases and 6137 (88.2%) were controls. A total of 1438 patients were Black (20.1%) and 4314 were White (62.0%); 3534 were female (50.8%). Median age was 72 years (IQR, 66-80 years) and 1829 adults (26.3%) were immunocompromised. A total of 63 cases (7.7%) and 966 controls (15.7%) were vaccinated. Estimated vaccine effectiveness against RSV-associated hospitalization was 58% (95% CI, 45%-68%) during 2 seasons and 69% (95% CI, 52%-81%) for same-season vaccination vs 48% (95% CI, 27%-63%; P = .06) for prior-season vaccination. Estimated vaccine effectiveness during 2 seasons was significantly lower among immunocompromised adults (30%; 95% CI, -9% to 55%) than immunocompetent adults (67%; 95% CI, 53%-77%; P = .02) and among those with cardiovascular disease (56%; 95% CI, 32%-72%) vs without (80%; 95% CI, 62%-90%; P = .03).

Conclusions and relevance: Respiratory syncytial virus vaccines prevented RSV-associated hospitalization during 2 seasons, although effectiveness was lower in patients with immunocompromise and cardiovascular disease than in those without these conditions. Ongoing monitoring is needed to determine the optimal RSV revaccination interval.

Figure 1.. Inclusion Criteria for Hospitalized Adults Aged 60 Years or Older in the Test-Negative, Case-Control Analysis of Respiratory Syncytial Virus (RSV) Vaccine Effectiveness

^aExclusions are not mutually exclusive and therefore exceed 100%. ^bRespiratory syncytial virus–positive case patients who also tested positive for SARS-CoV-2, influenza virus, or both were excluded because RSV vaccination would not be expected to prevent hospitalization caused by other respiratory viruses; RSV-negative control patients who tested positive for SARS-CoV-2, influenza virus, or both were excluded to minimize bias due to correlated vaccination behaviors among these vaccine-preventable respiratory viruses.

Figure 2.. Respiratory Syncytial Virus (RSV)–Associated Hospitalizations and Vaccinations

A, Number of RSV-associated hospitalizations by month of RSV-associated hospitalization and RSV subtype. Only RSV-associated hospitalizations occurring during season 1 (October 1, 2023-March 31, 2024) and season 2 (October 1, 2024-April 30, 2025) were included in this analysis. B, Number of RSV vaccinations by month of RSV vaccine receipt among adults hospitalized during season 1 and season 2. Patients who received 2 doses of RSV vaccine (n = 25) were excluded from this analysis.

Figure 3.. Respiratory Syncytial Virus (RSV) Vaccine Effectiveness Against RSV-Associated Hospitalization or In-Hospital Outcomes Among Adults Aged 60 Years or Older by Subgroups During 2 RSV Seasons

^aRespiratory syncytial virus vaccine effectiveness (VE) was estimated by comparing the odds of RSV vaccination between RSV-positive case patients and RSV-negative control patients, using multivariable logistic regression. The odds ratios were adjusted for a base set of a priori variables, including age, sex, race and ethnicity, US Department of Health and Human Services region, and calendar month and year of admission. The adjusted odds ratio of RSV vaccination was used to estimate RSV VE as (1 – adjusted odds ratio) × 100%. ^bStatistical differences between VE estimates were assessed in 2 ways. When estimates were compared by age group or underlying medical conditions, an interaction term between vaccination and subgroup was added to the base model, and a χ² test was used to assess statistical significance. For comparisons of VE by RSV vaccine product, 3 exposure levels were used (reference: unvaccinated, vaccinated with Arexvy [GSK], and vaccinated with Abrysvo [Pfizer]) and a Wald contrast test was conducted between product coefficients in the logistic regression model. Statistically significant differences were defined by 2-sided P < .05. NA indicates not applicable. ^cModerate or severe immunocompromise was defined as active solid tumor or hematologic malignancy (ie, newly diagnosed malignancy or treatment for a malignancy within the previous 6 months), solid organ transplant, hematopoietic cell transplant, HIV infection, primary immunodeficiency, use of immunosuppressive medication in the past 30 days, or other conditions that cause moderate or severe immunosuppression. ^dAny RSV vaccine includes RSV vaccinations with known product type (Arexvy or Abrysvo), as well as those with unknown product type. ^eAcute respiratory failure was defined as new receipt of high-flow nasal cannula, noninvasive ventilation, or invasive mechanical ventilation. ^fAcute organ failure was defined as a composite of acute respiratory failure (as defined earlier) or cardiovascular failure (defined as use of a vasopressor medication) or acute kidney failure (defined as new receipt of any type of kidney replacement therapy). ^gA sensitivity analysis in which patients with human metapneumovirus (hMPV) were excluded from cases and controls was conducted to assess the potential effect of cross-protection of RSV vaccines against hMPV because both viruses belong to the Pneumoviridae family. An additional sensitivity analysis was conducted in which VE estimates stratified by age groups were restricted to immunocompetent adults because moderately or severely immunocompromising conditions may be disproportionately higher among adults aged 60 to 74 years than those aged 75 years or older.

Figure 4.. Respiratory Syncytial Virus (RSV) Vaccine Effectiveness Against RSV-Associated Hospitalization Among Adults Aged 60 Years or Older by Time Since RSV Vaccination^a and Subgroups

^aSame season of RSV vaccination was defined as RSV vaccinations that occurred from August 1, 2023, through March 31, 2024, for patients hospitalized during October 1, 2023, through March 31, 2024, or as RSV vaccinations that occurred from August 1, 2024, through April 30, 2025, for patients hospitalized during October 1, 2024, through April 30, 2025. Prior season of RSV vaccination was defined for patients hospitalized during October 1, 2024, through April 30, 2025, who received RSV vaccine before August 1, 2024. ^bRespiratory syncytial virus vaccine effectiveness (VE) was estimated by comparing the odds of RSV vaccination between RSV-positive case patients and RSV-negative control patients, using multivariable logistic regression. The odds ratios were adjusted for a base set of a priori variables, including age, sex, race and ethnicity, US Department of Health and Human Services region, and calendar month and year of admission. The adjusted odds ratio of RSV vaccination was used to estimate RSV VE as (1 – adjusted odds ratio) × 100%. ^cStatistical differences between VE estimates by season of vaccination relative to hospitalization were compared using 3 exposure levels (reference: unvaccinated, same-season vaccination, or prior-season vaccination), and a Wald contrast test was conducted between same- and prior-season coefficients in the logistic regression model. Statistical significance was defined by 2-sided P < .05. Patients with cardiovascular disease and chronic lung disease were restricted to immunocompetent adults. ^dModerate or severe immunocompromise was defined as active solid tumor or hematologic malignancy (ie, newly diagnosed malignancy or treatment for a malignancy within the previous 6 months), solid organ transplant, hematopoietic cell transplant, HIV infection, primary immunodeficiency, use of immunosuppressive medication in the past 30 days, or other conditions that cause moderate or severe immunosuppression.