The Protective Value of RSV Vaccines in Older Adults: A Deeper Dive

In just over a year, not one but three novel vaccines that reduce the risk of respiratory syncytial virus (RSV) infection-associated lower respiratory tract disease (LRTD) – GSK’s AREXVY, Pfizer’s ABRYSVO and most recently Moderna’s mRESVIA – have been approved for marketing and will be available for the upcoming 2024-2025 RSV season.*  Large-scale clinical trial results have demonstrated that each has robust vaccine efficacy against development of LRTD in persons aged 60 years and older; all three vaccines are indicated solely for prevention of RSV-caused LRTD solely in this older 60-plus age group.^1,2,3

A consumer fact sheet prepared by the U.S. Centers for Disease Control and Prevention (CDC) also warns older adults, in large block letters, that RSV can cause pneumonia and other serious illness, and annually accounts for 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths.⁴

Yet for the majority of adults aged 60 years and older, an RSV infection will result in only mild cold-like symptoms. “Talk to your healthcare provider to see if vaccination is right for you,” the CDC recommends.⁵ This advice obviously diverges from the CDC’s far more straightforward recommendation that, with rare exceptions, every adult (as well as every child aged 6 months and older) should get a seasonal influenza vaccination.

As of mid-May of this year, nearly three-quarters of adults aged 65 and older have received a seasonal influenza vaccine, while only about one-quarter of those aged 60 years and older report receipt of an RSV vaccine.⁶ While this comparatively low rate of RSV vaccine adoption can be explained in part by its newness, leaving the vaccination decision to the discretion of the individual and his or her healthcare provider likely plays a part as well. 

This elective aspect of RSV vaccination may be particularly problematic for older adults who:

• Have underlying health conditions that place them at increased risk of severe RSV disease, but are unaware of it because they don’t access this information;

• Believe that, because RSV vaccination is elective, they are likely at minimal risk of severe or life-threatening RSV disease; or

• Neglect to inquire with their healthcare provider about the advisability of getting the RSV vaccine.

Marketing materials for ABRYSVO do helpfully alert older adults that “as you age, your immune system weakens, leaving you vulnerable to a serious case of RSV,” and “the presence of underlying medical conditions such as asthma, COPD, diabetes or heart disease can put you at increased risk of severe RSV.”⁷ AREXVY ads similarly explain that “RSV can be serious for those aged 60 years and older, including those with asthma, diabetes, chronic obstructive pulmonary disease (COPD) or chronic heart failure.”⁸ 

For older adults who prioritize their health and place their trust in their physician and pharmacist for advice, these kinds of broad-based warnings about the risks of RSV infection are undoubtedly helpful to make the decision to get vaccinated. But qualitative cautionary messages of this nature may be less effective in persuading many millions of other older adults who may be hesitant for one reason or another, or who remain skeptical in the absence of hard evidence. 

CDC epidemiologists have now addressed this “hard information” gap with the publication of newly completed research identifying which underlying chronic conditions in older adults increase the risk of hospitalization for RSV infection and, more importantly, by how much. 

CDC Surveillance Generates Answers

Leveraging data acquired through its Behavioral Risk Factor Surveillance System and its RSV-Associated Hospitalization Surveillance Network (RSV-NET) covering nearly nine percent of the U.S. population, CDC investigators calculated RSV-associated hospitalization rates over the 2017-2018 season for community-dwelling adults with nine different chronic conditions in three defined age groups (50-64, 65-74 and ≥75 years):⁹ 

• Asthma

• Chronic kidney disease (CKD)

• COPD

• Coronary artery disease (CAD)

• Current smoking

• Diabetes mellitus

• Obesity (body mass index 30-39 kg/m2)

• Severe obesity (body mass index ≥40 kg/m2)

• Stroke history

In addition to estimating RSV-linked hospitalization rates for each of these chronic conditions in persons aged 65-74 years (Figure 1) and ≥75 years (Figure 2), for each of these age groups CDC epidemiologists additionally determined adjusted rate ratios (aRRs) relative to their peers without each condition. 

In both age groups, the presence of CKD was associated with a six-fold higher aRR of RSV-associated hospitalization relative to persons without CKD. But in adults aged 65-74 years and ≥75 years with comorbid CKD and CAD, the respective aRRs jumped to 10.5 and 7.9 compared to individuals with neither condition, albeit with wide confidence intervals reflecting the limitations of the study sample size.

In both older age groups, presence of COPD, severe obesity and asthma were each associated with a three- to four-fold higher risk that RSV infection would result in hospitalization. Existing CAD, diabetes and current smoking status roughly doubled the risk of hospitalization in adults aged 65-74 years, while only presence of CAD accounted for a similarly increased risk in those aged ≥75 years. 

Predictably, the overall RSV-related hospitalization rate was lowest for all adults aged 50-64 years, roughly one-third of the rate for all adults aged 65-74 years and eight-fold lower than the rate for all adults aged ≥75 years. This pattern of increasing RSV hospitalization rates with advancing age applied for each of the examined chronic conditions that commonly affect older individuals (Figure 3).⁹

On close examination, these CDC data also reveal that the risk of RSV-associated hospitalization for persons aged 50-64 years living with CKD, COPD, CAD, asthma and diabetes rivals or exceeds RSV hospitalization risk in the overall population of persons aged 65-74 years. 

At present, none of the three vaccines are indicated for any of the roughly two-thirds of individuals in the 50-64 year age cohort who are 50-59 years of age, regardless of whether they have these chronic comorbidities or not.  But all three manufacturers are currently conducting clinical trials to investigate the protective effect of their RSV vaccines in adults under age 60 years who have chronic conditions that increase their risk of severe RSV disease.

Acute Cardiac Events in RSV Hospitalizations 

If the prospect that an RSV infection could lead to hospitalization isn’t quite enough to persuade some older at-risk patients to get vaccinated, creating awareness of the most serious adverse outcomes during an RSV-associated hospitalization might change some minds. To that end, another newly published epidemiologic study by the CDC and state-level public health collaborators has now documented a surprisingly high rate of acute cardiac events in middle-aged and elderly U.S. adults hospitalized with a laboratory-confirmed RSV infection. 

The Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET) abstracted medical record data from 6,248 hospitalized persons with RSV aged 50 years or older (median 72.7 years) in 12 states over five RSV seasons, ending in the 2022-2023 season. Just over one-half (56.4 percent) of patients in this cross-sectional sample had underlying cardiovascular disease. 

Nearly one-quarter (22.4 percent) of these adults hospitalized with an RSV infection experienced an acute cardiac event, including one in 12 (8.5 percent) adults with no documented underlying cardiovascular (CV) disease and one in three (33.0 percent) with underlying CV disease (Table). Acute heart failure and acute ischemic heart disease were also common occurrences, again at far higher rates in patients with pre-existing CV disease.

Nearly one in five RSV-infected hospitalized adults (18.6 percent) required admission to the intensive care unit, and one in 20 (4.9 percent) died during the course of their hospital stay. Unsurprisingly, older age was associated with increasing risk of an acute cardiac event; compared to hospitalized patients aged 50-64 years, the aRRs for those aged 65-74, 75-84 and ≥85 years were 1.1, 1.2 and 1.44, respectively.

On the Way: More Evidence and Expanded Approvals 

Now that safe and effective RSV vaccines are finally available, more evidence of their direct health benefits in older Americans will be forthcoming. It is likely as well that FDA will eventually expand the marketing approvals of these vaccines to include adults under age 60 with chronic conditions demonstrated to importantly increase the risk of RSV-associated LRTD and hospitalization.

For those patients who are initially skeptical or unsure whether to get the RSV jab, sharing epidemiologic data that quantifies risks of severe illness and hospitalization can help make RSV vaccines’ protective value clearer and more compelling. And for your patients at increased risk due to underlying chronic comorbidities, it is a conversation particularly well worth having.