RSV has long been recognised as a leading cause of respiratory tract infections in infants and young children. However, recent research has also shed light on the significant burden of RSV infections in adults.5,9 Based on data from the Global Burden of Disease report, which covers 204 countries and territories, the mortality rate for individuals aged 70 years and older in 2019 exceeded that of other age groups. It is worth noting that the mortality rate for people aged 70 years and older compared to infants under 5 years old increased from 0.57 in 1990 to 1.85 in 2019.12 Understanding the epidemiology of RSV in adults is crucial to identifying high-risk populations and implementing effective preventive measures, such as vaccination.

RSV peaks are typically observed during the fall and winter, but inter-seasonal RSV activity exists, and its reservoir is exclusively human.13 Occupational exposure is a crucial factor in the epidemiology of RSV in adults. Healthcare and daycare workers are at a higher risk of contracting RSV due to their frequent contact with infected individuals. These occupations play a critical role in the transmission dynamics of RSV, as infected healthcare workers can spread the virus within healthcare settings and vulnerable patient populations.14–16

Adults aged 60 years and older, especially those residing in long-term care facilities or nursing homes, are at increased risk of severe RSV-related illness.17 A recent meta-analysis found that in adults aged 60 years and older, the attack rate for RSV-associated acute respiratory infection was estimated at 1.62%; the hospitalisation attack rate was 0.15%, and the in-hospital case fatality rate (hCFR) was 7.13%.3 In Spain, Heppe-Montero et al. estimated an hCFR of 7.91% for patients aged 60 years or older.18

Additionally, age-related comorbidities, such as chronic obstructive pulmonary disease (COPD), congestive heart failure, stroke, chronic kidney disease and diabetes, further heighten the risk of severe RSV infections and the need for hospitalisation.19–23 Furthermore, individuals with compromised immune systems, such as those undergoing immunosuppressive therapy, solid organ transplant recipients, people with HIV infection, and especially those with haematologic malignancies undergoing chemotherapy, are at an elevated risk of severe RSV infections.24 The chronic use of inhaled corticosteroids has also been associated with the increased risk of RSV pneumonia (aOR 2.08 [95% CI: 1.39–3.09]).25 These individuals often experience more prolonged and severe illness and are at an increased risk of complications, including hospitalisation and death.26–28

Complications include bacterial co-infection in up to 29% of adults hospitalised for RSV pneumonia, the most common pathogens being Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.29 This co-infection rate is even higher than in influenza patients, estimated to occur in 20% of patients.30 RSV infection may also be complicated by cardiovascular events, including acute coronary syndrome, worsening congestive heart failure and arrhythmias in 14–22%.31 Finally, acute functional loss has been associated with a significant short- and long-term reduction in quality of life, which may last for months.8,32

In sum, RSV infections in adults represent a significant public health concern and have a substantial impact on morbidity, mortality, and healthcare utilisation. Older adults, individuals with chronic medical conditions, immunocompromised individuals, and those with occupational exposure face an elevated risk of severe RSV-related illness14–16,18,33–36

RSV infection in adults can present with a wide spectrum of clinical manifestations, ranging from mild respiratory symptoms to severe lower respiratory tract infections. Individual risk factors, comorbidities, and immunological status influence the clinical presentation of RSV in adults.37 The most common clinical symptoms of RSV infection in adults include cough, rhinorrhoea (runny nose), sore throat, nasal congestion, and fever. These symptoms often resemble those of other respiratory viral infections, so clinical diagnosis is challenging without laboratory confirmation. RSV infection may be mistaken for a common cold or influenza, especially during seasonal peaks of respiratory viral activity.38,39

While RSV infections in adults can be self-limiting and resolve without complications, they can also progress to more severe respiratory illnesses, including pneumonia, as a complication of RSV infection that may require hospitalisation.22,40 In some individuals, particularly those with underlying chronic respiratory conditions, RSV infection can lead to exacerbations of pre-existing conditions, such as COPD or asthma.41 In severe cases, RSV infection may result in lower respiratory tract infections, such as bronchiolitis and pneumonia. Bronchiolitis is more commonly observed in infants and young children but can also occur in adults, especially those with compromised lung function or immunocompromised status.42 RSV is also a cause of pneumonia in 49.3% of patients with confirmed RSV infection, primarily in the form of consolidations (23.8%) or ground-glass opacities (19.9%).40

RSV infections in the elderly are frequent and more severe than those with influenza A/B, especially in vulnerable populations, and can result in hospitalisation and, in rare cases, lead to fatal outcomes. These severe outcomes are more likely in individuals with multiple risk factors, advanced age, and significant comorbidities.4,22

In summary, RSV infection in adults has different presentations, ranging from asymptomatic or mild respiratory symptoms to exacerbations of underlying chronic conditions and severe lower respiratory tract infections, such as bronchiolitis and pneumonia. Clinical manifestations can vary widely, and individual risk factors and comorbidities influence the severity of illness. Early identification through efficient diagnostic testing, suitable treatment and specific preventive measures like vaccination are essential in reducing the morbidity and mortality linked to RSV infection in adults.

RSV is a negative-sense, non-segmented RNA virus of more than 15,000 nucleotides. Unlike influenza viruses, it cannot reassort segments, so a large-scale pandemic is unlikely.43 RSV has two major specific antigenic subgroups (A and B) that differ in a number of proteins, but the major genetic diversity lies within the attachment glycoprotein G. However, glycoprotein F is highly conserved between RSVA and RSVB, making it an ideal candidate as a vaccine antigen, once stabilised in its “pre-fusion” structural conformation, which induces more potent neutralising antibodies by presenting more important epitopes.43,44

Clinical features in adults are not sufficiently helpful in distinguishing RSV from other respiratory agents; therefore, laboratory confirmation may be required. Molecular testing, such as polymerase chain reaction (PCR)-based assays, are rapid, highly sensitive and specific, making them the preferred tool in hospitalised adult patients, particularly when using lower respiratory tract samples. The preferred sample for detecting RSV in adults is a nasopharyngeal swab, but adding additional samples such as saliva, sputum, and serology increases diagnosis accuracy by 2.6-fold.45 Multiplex PCR-based assays enable the simultaneous detection of several respiratory pathogens, albeit at a higher cost. Rapid antigen detection tests (RADTs) provide a quicker, cheaper and more useful point-of-care diagnostic tool, although their sensitivity is less than 10% compared to serological tests and PCR. Immunochromatographic assays targeting RSV F-glycoprotein are used for most RADTs.46 Viral culture is time-consuming and demands trained staff, limiting it to reference labs. Serology offers limited value for immediate diagnosis or patient care, yet when paired with PCR in acute and convalescent phases, its sensitivity is heightened beyond that of viral culture. Whole-genome sequencing and next-generation sequencing techniques are presently unavailable for clinical purposes. These techniques are intended mostly for public health research due to their capacity for detecting evolutionary diversity and potential transmission patterns.47

Historically, the development of an RSV vaccine has been challenging.48 In light of recent advances in understanding the biology and structure of the RSV virus, particularly the importance of the pre-fusion configuration of the F antigen (Pre-F Ag),49 numerous vaccine candidates have been developed and tested. Each candidate uses a distinct but all use Pre-F Ag. Here, we discuss the current status of RSV vaccine development for the elderly population and highlight key characteristics of various vaccine candidates (Table 1).

The age-based indication strategy involves recommending RSV vaccination for all individuals within a specific age range, regardless of their individual risk levels or underlying conditions. This approach does not require identifying and targeting specific high-risk groups, making it a convenient and efficient strategy. The decision on the age threshold should balance the greatest impact on disease burden and its efficiency.67

The strategy of targeting high-risk groups involves prioritising RSV vaccination for populations at higher risk of severe RSV infection or its complications (Table 4). The main justifications for a strategy of targeting high-risk groups would be: (1) high-risk groups, such as older adults, people with chronic respiratory diseases, immunocompromised individuals and healthcare workers, are more likely to experience severe RSV infection or transmit the virus to vulnerable populations68,69; (2) limited vaccine supply or higher vaccine costs may necessitate prioritising high-risk groups to achieve the greatest public health impact; and (3) targeting high-risk groups allows for a more targeted approach, ensuring that those most susceptible to severe RSV illness are protected.70

To ensure maximum protection, it is important to consider the following:

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  Seasonal outbreaks: RSV infection typically occurs in seasonal outbreaks, with the highest incidence in temperate regions occurring during the autumn and winter months. However, RSV activity can vary geographically. Therefore, local surveillance data should be considered when determining the optimal timing of vaccination.

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  Ideal timing: Vaccination should ideally be administered before the onset of the RSV season to provide the highest level of protection. However, considering that the currently available vaccines induce protection for at least two seasons,53,54 timing should be as early as possible for those eligible, irrespective of RSV activity.

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  Vaccine type: The schedule may vary depending on the specific vaccine. This includes the number of doses required and the interval between doses. Both currently approved RSV vaccines are recommended for administration as a single dose.

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  Booster doses: Evidence to determine the need for revaccination is not currently available.

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  Recommended timing and schedules: RSV vaccination in adults can be seamlessly integrated into routine immunisation schedules by considering the recommended timing and schedules of other vaccines. This allows for efficient and convenient administration of multiple vaccines.

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  Co-administration with other vaccines: By combining vaccines, individuals can receive multiple vaccinations during a single healthcare visit, reducing the need for additional appointments and associated costs. Both RSVpreF3 (Arexvy, GSK) and RSVpreF (Abrysvo, Pfizer) can be administered concurrently with the seasonal influenza vaccine. RSVpreF3 shows non-inferior immune responses in adults aged 60 and older, but co-administration resulted in numerically lower RSV A and B neutralising titres and influenza A and B hemagglutination inhibition titres, with unknown clinical relevance. RSVpreF, studied in adults aged 65 and older, also demonstrated non-inferior immune responses, but co-administration with adjuvanted influenza vaccine showed similar reductions. RSVpreF requires a two-week interval before tetanus, diphtheria, and acellular pertussis vaccine, and is associated with lower immune responses to pertussis components in co-administration; the clinical relevance remains unknown.50,51 Despite the lack of specific studies, public health authorities can decide to authorise the co-administration of RSV with other vaccines, favouring the opportunity of vaccination against the eventual immunological interference.53,54