BACKGROUND
Respiratory syncytial virus (RSV) is a common seasonal virus transmitted via respiratory droplets.1,2 Symptoms typically begin within 6 days of infection in adults; however, individuals are often contagious before symptoms manifest.1,3 Common symptoms of RSV infection include runny nose, coughing, sneezing, wheezing, decreased appetite, and fever.3 In some cases, RSV can lead to severe illness, especially lung infections and worsening of prior lung and cardiac conditions.4
RSV-associated lower respiratory tract infections (LRTI) cause significant morbidity and mortality. Globally, the World Health Organization estimates 33 million RSV-associated LRTI occur each year.5 In the United States, the Centers for Disease Control and Prevention (CDC) estimates that RSV results in between 60 000 to 160 000 hospitalizations and 6000 to 10 000 deaths annually among adults aged 65 years and older.6
Individuals over age 65 with chronic medical conditions, especially lung and cardiac disease, are at higher risk of hospitalization due to RSV.9,14 Among this demographic, up to 32% will require hospitalization and up to 26% will require intensive care for supportive treatment of their RSV infection.13
Testing for RSV, which involves sampling of nasopharyngeal secretions, is not consistently performed in clinical settings, especially for older adults.7,8 Additionally, older adults can have lower than average viral titers, leading to increased false-negative results and an underestimation of RSV infection rates.7 For both older adults and individuals with chronic medical conditions, the true burden of RSV is underestimated.9 Thus, fewer than 5% of the estimated hospitalizations from RSV infection are properly captured for individuals greater than 65 years of age.10
Currently, only supportive treatment is available for RSV infections.11 Despite under reporting, RSV-coded hospitalization rates in older adults have increased in the last decade.12 Once hospitalized with RSV, between 10% to 31% of adults require intensive care, and as many as 17% require mechanical ventilation.13 Mortality rates of older adults hospitalized with RSV range from 11% to 18%.13
In recent decades, RSV research has focused on preventative therapies, particularly vaccination. Vaccination of older adults aims to reduce infection severity, hospitalization rates, medical complications, and mortality rates.15 Additionally, vaccinating against RSV is cost effective.16 “To have the ability to reduce the risk of severe disease from RSV can make a major impact on a very, very common virus that does place burdens on hospitals and leads to what will become now preventable deaths,” states Amesh Adalja, an infectious disease physician at the Johns Hopkins Center for Health Security.17 In 2023, The US Food and Drug Administration (FDA) approved the first vaccines for the prevention of RSV.19 Since then, RSV vaccination has been recommended for older adults in the United States.19 As of April 2024, there were 42 registered clinical trials for prevention of RSV in older adults, including 10 vaccine candidates.18
EDUCATIONAL ANALYSIS
Gap #1: Clinicians may be unaware of the 3 vaccines currently available for prevention of RSV in older adults
Learning Objective #1: Evaluate the 3 FDA-approved vaccines available for prevention of RSV in older adults
Dan Barouch, MD, immunologist at Harvard Medical School, stated, “It’s a very welcome advance to have not one but several prophylactic interventions for RSV.”17 Currently, 3 vaccinations against RSV are approved for use in the United States for adults aged 60 year and older; 2 are RSV protein subunits and one is a modified messenger ribonucleic acid (mRNA) encoding RSV protein.20 The FDA approved RSVpreF3 and RSVpreF in May of 2023, and mRNA RSV in May of 2024.19,21
RSVpreF3 is FDA approved for the prevention of RSV-associated LRTI in adults over 60 years of age and adults 50 to 59 years of age who are at increased risk.22 The vaccine is a protein subunit.23 RSVPreF3 was 94.1% effective against severe RSV-associated LRTI, and 77% to 83% effective in preventing RSV-associated hospitalizations or emergency room visits.20 The most common adverse reactions following vaccination with RSVpreF3, in order of frequency, are pain at the injection site, fatigue, myalgia, headache and arthralgia.22
RSVpreF is FDA approved for prevention of RSV-associated LRTI in adults aged 60 years and older, as well as pregnant individuals between 32 and 36 weeks of gestation.24 The vaccine is also a protein subunit.23 RESVpreF was 66.7% effective against severe RSV-associated LRTI and 73% to 79% effective in preventing RSV-associated hospitalizations or emergency room visits.20 The most common adverse reactions following vaccination with RSVpreF, in order of frequency, are fatigue, headache, pain at the injection site, and myalgia.24
The mRNA RSV vaccine is FDA approved for the prevention of RSV-associated LRTI in individuals aged 60 years and older.25 The vaccine is an mRNA encoding RSV protein; it creates RSV proteins once within the body.25 The mRNA RVA vaccine demonstrated 78.7% efficacy against laboratory-confirmed, RSV-associated LRTI with 2 symptoms.26 The most common adverse reactions following vaccination with mRNA RSV, in order of frequency, are pain at the injection site, fatigue, headache, myalgia, arthralgia, axillary swelling, and chills.25 All three vaccines are administered intramuscularly, at a dose of 0.5 mL.22,24,25 The vaccines should not be given to those with a history of severe allergic reaction to any component of the vaccines.22,24,25 The 3 RSV vaccines protect against severe RSV infection for at least 2 RSV seasons.20
Gap #2: Clinicians may be unaware of the current guidelines for RSV vaccination in older adults, and how they differ from previous guidelines
Learning Objective #2: Review the 2024-2025 RSV vaccine guidelines, comparing and contrasting to previous guidelines
RSV vaccination was first available and recommended in the United States in the fall of 2023.19 The first guidelines, released by the Advisory Committee on Immunization Practices (ACIP) in June 2023, recommended individuals aged 60 years and over engage in shared clinical decision-making with their physicians to determine if RSV vaccination with either RESVpreF or RESVpreF3 was appropriate.19, 21 The guideline outlined those who were at highest risk for RSV, including individuals with chronic disease, advanced age, and those living in retirement or nursing homes.21
Since the 2023 guidelines were released, new efficacy and safety data regarding the 2 available vaccines have been published, and a new vaccine, mRNA RVA, has been approved. Furthermore, it was noted that shared clinical decision making was difficult to implement.19 As a result, in June of 2024, the ACIP released new guidelines for the 2024-2025 RSV season.19 The new recommendations focus on maximizing RSV vaccination uptake in those individuals most at risk, while reducing the barriers created by the shared clinical decision-making approach.19
Under the new guidelines, the ACIP recommends a single dose of RSV vaccine for all adults aged 75 years or older.19,20 Vaccination of adults aged 60 to 74 years of age with increased risk of severe RSV is also recommended.19,20
The new guidelines thoroughly outline the criteria for determining increased risk of severe RSV in adults aged 60 to 74 years of age. These include chronic cardiovascular disease, chronic lung disease, end-stage renal disease, diabetes mellitus with complications or requiring specific treatments, certain neurologic or neuromuscular conditions, chronic liver disease, chronic hematologic disorders, and moderate or severe immune compromise.19 Patients over 60 years of age residing in nursing homes are also considered high risk, as is anyone over 60 years of age with a medical condition not listed in the guideline that a physician deems to be at elevated risk of RSV infection.19
RSV vaccination is approved with either RESVpreF, RESVpreF3, or mRNA RVA.19 The CDC endorses all 3 RSV vaccines equally for eligible adults.6
RSV vaccination is most effective if received before the viral season commences; providers are encouraged to give RSV vaccines in late summer or early fall.6,20,21 RSV vaccination is not an annual vaccine. So far, the vaccine appears to provide protection from severe disease for at least 2 years.20 Individuals who received a dose of RSV vaccination last season should not receive another dose.19
It is acceptable to co-administer RSV vaccination with other adult vaccinations, including those for influenza or coronavirus.21 However, it was noted that co-administration of vaccines can increase local and systemic reactions.20
Post-licensure surveillance data suggest a potentially increased risk of Guillain-Barré syndrome (GBS) after RSV vaccination with RSVpreF3 and RSVpreF.19 This risk was not observed with mRNA RSV vaccination.6 As such, ACIP recommends counseling patients about the increased of risk of GBS prior to administration of either RSVpreF3 or RSVpreF vaccines.19 Furthermore, the guidelines recommend against administration of RSV vaccines in individuals aged 50 to 59 years.20
Gap #3: Clinicians may be unaware of current public attitudes regarding RSV and RSV vaccination
Learning Objective #3: Review public attitudes regarding RSV and RSV vaccination since vaccination has become available
RSV is not as prominent in public discourse as are other viruses such as influenza and coronavirus. Nick Stucky, MD, an infectious diseases physician at Providence Portland Medical Center stated, “In general, people aren’t as aware of RSV, so that makes creating awareness of the vaccines even more challenging. Because severe RSV disease is concentrated in vulnerable populations, it often isn’t something that is experienced or known by the general public.”17
By May of 2024, after the conclusion of the first season of RSV vaccination in the United States, over 80% of eligible adults had heard of RSV and knew that vaccination was available, but only 26% reported having receiving an RSV vaccine.27 Reasons for not receiving RSV vaccination included lack of knowledge of the disease, lack of knowledge of the vaccination, concerns about vaccination safety, and lack of discussion with their health care provider.27
Even among healthcare providers, RSV is not routinely considered. “Though the infection [RSV] is a common cause of respiratory disease, it is often overlooked in adults,” stated Michael Melgar, MD, a medical officer with the CDC National Center for Immunization and Respiratory Diseases.”8 Increasing healthcare providers’ awareness of RSV prevalence and the prevention options available can lead to healthcare providers providing their patients with more robust education concerning RSV immunization.
RSV vaccination is preferable in the fall, which coincides with influenza and coronavirus vaccination. Individuals, including those at highest risk for infection, may be hesitant to get so many vaccines at once. Joseph Kanter, a medical official for Louisiana’s health department, stated, “One of the comments that we have begun to hear is that ‘this is a lot,’ and I understand that.”17
After one season of vaccination, patients with chronic medical conditions who were at highest risk of severe RSV infection were only modestly more vaccinated against RSV than adults without comorbidities.19 It is anticipated that the change in guidelines away from shared clinical decision-making will allow health care providers to make stronger recommendations to in favor of RSV vaccination for this subset of the population, thereby ensuring those at highest risk are most protected.
Despite these hurdles, many healthcare providers are adapting RSV vaccination of older adults as part of their standard of care. Model-based analysis estimate that RSV vaccination of older adults could prevent as many as 20% to 40% of RSV-associated hospitalizations and deaths.28 By furthering their knowledge of RSV vaccinations and following ACIP guidelines, healthcare providers can improve RSV vaccination rates in older adults, which will lead to decreased patient morbidity and mortality.
CONCLUSION
RSV causes seasonal illness in the United States. Elderly individuals, especially those with comorbidities, are at risk for severe RSV illness, which can lead to significant morbidity and mortality. While no cure exists for RSV, vaccines are now available and have been shown to decrease RSV-associated hospitalizations and deaths. The 3 vaccines currently available in the United States are RSVpreF3, RSVpreF, mRNA RSV; all
3 are FDA-approved for individuals over the age of 60. New guidelines released by the ACIP in June of 2024 recommend a single dose of RSV vaccine for all adults over the age of 75, as well as for adults aged 60-74 years with increased risk of severe RSV.
In order to best assist their patients, physicians must be aware of the new RSV vaccines available and be well-versed in their mechanisms of action. By understanding the new recommendations regarding RSV vaccine administration, physicians can best assess which patients are eligible for RSV vaccination, thereby ensuring those at highest risk are protected. Lastly, by better acquainting themselves with public attitudes towards both RSV and the RSV vaccines, physicians can better shape their discussions with their patients.
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26. Das R. Update on Moderna’s RSV Vaccine, mRESVIA (mRNA-1345), in Adults ≥60 Years of Age. Presented at: Advisory Committee on Immunization Practices Meeting; June 26-28,2024; Atlanta, GA. Accessed September 18, 2024. https://stacks.cdc.gov/view/cdc/157864
27. Stulpin C. Survey shows low RSV vaccine uptake among older adults in the US. Healio. May 21, 2024. Accessed September 18, 2024. https://www.healio.com/news/infectious-disease/20240521/survey shows-low-rsv-vaccine-uptake-among-older-adults-in-the-us
28. Crist C. For Which Adults Are RSV Vaccination Programs Cost-Effective? Medscape. September 13, 2024. Accessed September 18, 2024. https://www.medscape.com/viewarticle/which-adults-are-rsv vaccination-programs-cost-effective-2024a1000gn8