RSV: Burden of Disease in Older Adults

Funded through sponsorship by Pfizer Private Limited. Medscape approached Pfizer Private Limited to fund the production of this editorial article. Please see bottom of page for full disclaimer.

Introduction

RSV infection is recognised as a serious paediatric infection and a leading cause of hospitalisation in infants.^[1] RSV can also cause lower respiratory tract infection in adults over 65 leading to pneumonia and exacerbating underlying conditions.^[2,3]

Data suggests that RSV infection is responsible for 214,000 hospitalisations in industrialized countries (while data for developing countries is missing), and it is estimated that there are over 14,000 in-hospital deaths in older adults worldwide every year.^[3] However, because RSV causes mild signs and symptoms in most adults,^[4] this virus may not be viewed as a high priority by practicing clinicians and its burden is probably underestimated.^[5]

Presently, there is no effective treatment for RSV, and therefore prevention is key. The first RSV vaccines have recently been approved in multiple countries,^[6,7,8] and implementation is in its early stages. It is important to raise awareness of the disease burden in older adults and immunocompromised adult patients, so that practicing clinicians have sufficient information and evidence to recommend vaccination in these populations once it is made available by healthcare providers in their region.

The burden of disease in respiratory syncytial virus (RSV)

Julio Ramírez (JR): Do you think that estimates of the burden of RSV in older adults are accurate in your region? Do you have any data on prevalence and hospitalisation rates?

Ann R Falsey (AF): In Rochester, New York, US, the burden of RSV among older adults is underappreciated within the medical community; while paediatricians commonly recognise the significance of RSV, general practitioners and internists often overlook it.

According to a recent report from the Centers for Disease Control and Prevention, RSV is frequently identified as a significant cause of respiratory illness, accounting for 60,000–160,000 hospitalisations and 6,000–10,000 deaths annually.^[9] These figures may be underestimates due to the case definitions commonly used, which originate from influenza research programmes. Using a definition focused on influenza symptoms can overlook RSV cases, as fever is not usual in RSV infection.^[10]

Joel M Santiaguel (JS): In the Philippines, the burden of RSV is also underestimated in the context of severe respiratory illness. A review within our healthcare setting revealed that RSV was identified in only about 1% of all tested specimens. In larger hospitals, where viral respiratory panels are a standard procedure, RSV is more frequently identified as the primary causative agent of acute respiratory illness. The true prevalence may align with international data, suggesting a minimum rate of hospitalisation of 5%.^[11]

You Li (YL): In China awareness of RSV as an important respiratory pathogen in adults is still low. Outside respiratory specialists and paediatricians, healthcare professionals tend to underestimate the importance of RSV. The delay between the onset of symptoms and hospitalisation makes it difficult to estimate the community-level burden of RSV. Most existing evidence is from hospital settings, which test more frequently for RSV; we need more comprehensive data to gain a more accurate picture of the overall disease burden of RSV.

A recent systematic review, focusing on high-income countries, found that RSV accounts for approximately 8% of acute respiratory infections in hospitalised patients annually.^[12] When the limited RSV testing in China is considered, the true prevalence could be around 16.5%.^[12]

JR: How does burden of RSV vary between older adults and other age groups?

YL: The data is based primarily on data from high-income countries:

The highest rates of RSV-associated hospitalisations occur in infants (birth to 1 year), at approximately 2,000 per 100,000 of the population.^[13]
This is followed by rates in adults over 75 years, with several hundred hospital admissions per 100,000 of the population.^[13] However, this group had the highest mortality rate in 2019 (34.5 per 100,000).^[14]
Rates in the 1–5 age group and adults over 65 years were next, with 170 and 100–150 hospital admissions per 100,000 of the population, respectively.^[13]
The lowest hospitalisation rate, less than 10 per 100,000 of the population occurs in young people aged 5–17.^[13]

Clinical presentation of RSV and outcomes in older adults

JR: What are the most frequent clinical manifestations of RSV in adults?

AF: RSV presents with a broad range of symptoms ranging from minor cold symptoms to severe bronchitis, to respiratory failure in extreme cases.^[15] Asymptomatic cases are uncommon, accounting for less than 10% based on serologic testing.^[16]

Distinguishing between RSV and influenza by clinical presentation is challenging. RSV is more likely to cause nasal congestion, shortness of breath, wheezing, and sputum production, whereas influenza more frequently leads to fever and myalgia. PCR testing is required to accurately identify the underlying pathogen.^[15,17]

JS: From my clinical observations, when RSV causes upper respiratory tract infections in adults in the Philippines, the symptoms are usually mild due to partial immunity gained from previous exposure to RSV. More severe symptoms are limited to older adults with significant comorbidities.

YL: The wide range of symptoms in RSV infection is also the case in China. Without diagnostic tests it is virtually impossible to distinguish RSV from influenza or other viral infections, or indeed, bacterial respiratory tract infections.

JR: What demographic, environmental, or clinical factors place older adults at higher risk of poor outcomes?

JS: Severe symptoms are more common in patients who are immunocompromised or have significant underlying comorbidities such as asthma, chronic obstructive pulmonary disease (COPD), or cardiovascular disease.^[18] In these patients, an RSV infection should be considered as a potential cause for deterioration or poor control of symptoms despite medication.

Clinicians should always consider RSV in the differential diagnosis, both as a cause of primary infection and as a potential cause of co-infection with other pathogens.^[19]

AF: We do not fully understand the role of RSV infection as a precipitating factor for the decompensation of pre-existing medical conditions like heart failure.^[20] Clinicians may often overlook a recent upper respiratory infection as a possible trigger, but there is growing evidence that RSV infection can have significant cardiac complications, ranging from heart failure to arrhythmias and coronary artery disease.

This evolving area of research parallels earlier work on the association between influenza and cardiovascular events. Like influenza, RSV may induce a state of physiological stress or prothrombotic conditions that could contribute to cardiovascular complications. Additional research will be needed to inform clinical guidelines and patient care, particularly during the RSV season.

YL: RSV exhibits clear seasonality in most parts of the world, particularly in temperate regions. Increased vigilance is warranted during wetter and colder seasons to investigate RSV as a potential causative agent for severe pneumonia, especially in patients presenting with early influenza-like symptoms.

Diagnosis of RSV in older adults

JR: Do you perform specific RSV tests on older adults with respiratory symptoms?

AF: Although the clinical presentation of RSV in adults tends to be non-specific, diagnostic testing in the US is usually only performed when the RSV assay is part of a PCR panel requested to test for influenza or COVID-19.

JS: Diagnostic testing for RSV is usually conducted in the emergency department in the Philippines as part of a broad viral respiratory panel. This is often initiated for SARS-CoV-2 testing but it also picks up other coronaviruses, influenza A and B, and RSV among others. RSV testing must be considered when patients who are immunocompromised or have significant underlying comorbidities present with severe pneumonia or lower respiratory tract infection.

YL: Frequency of testing varies between facilities; very few tests for RSV are performed in emergency rooms or outpatient settings unless there is a specific reason. Most clinicians regard RSV testing as time-consuming and unlikely to influence management decisions. Larger hospitals have integrated commercial multiplex PCR kits that test every hospitalised respiratory patient for 13 different respiratory pathogens, including RSV. Since the onset of the COVID-19 pandemic, there has been a discernible shift towards increased RSV testing, with more hospitals applying this diagnostic tool.

JR: What are the main challenges faced by clinicians in diagnosing RSV in older adults?

AF: PCR analysis of a nasal swab remains the standard diagnostic approach for RSV. Viral culture is not possible as RSV does not survive well during transport. Rapid antigen tests (commonly employed for SARS-CoV-2) are of no use in RSV detection due to low viral titres in the nasal passages.

Clinicians must consider the timing and nature of symptoms; PCR of nasal secretions offers high sensitivity in outpatients presenting early in the course of illness with prominent nasal symptoms. However, the virus may have migrated to the lower airways in patients who have been symptomatic for several days, especially those requiring hospitalisation. In these cases, sputum may provide a higher-yield PCR sample.^[17] Emerging data also suggest that saliva may be a useful sample type.^[17] In research studies, acute and convalescent serology offers a comprehensive disease picture, but this approach is not practical for diagnosis in the clinic.

JS: The lack of awareness of RSV as a cause of respiratory infections, coupled with limited PCR testing in non-hospital settings and rural areas in the Philippines, increases the risk of missed or delayed diagnoses. This can have serious consequences for immunocompromised patients or older adults with comorbidities. Primary care physicians and other healthcare providers need education and training to understand the significance of RSV as a causative agent for severe pneumonia.

YL: Nasopharyngeal swabs, although common in other regions of the world, are rare in China. Throat swabs have become the norm, particularly in the context of COVID-19. However, the method used to collect clinical specimens varies across and within healthcare settings in China, which may affect the diagnostic accuracy for RSV infections.

JR: How do you determine if a patient with RSV has a bacterial co-infection?

AF: The challenges associated with differentiating between viral and bacterial respiratory infections in the clinical setting are well recognised. Some argue that a test for RSV is irrelevant because it does not change management, but I disagree. Knowing the infection is solely viral makes it less likely that an antibiotic would be prescribed unnecessarily, which is good antibiotic stewardship.

Sputum culture may be useful but bacterial contamination is common. Some new PCR panels include bacterial targets but can be difficult to interpret; we are still learning how to maximise their value. Measuring serum procalcitonin is not without its challenges but it can be useful in conjunction with viral testing.^[21] Emerging research on host gene expression profiles may also offer a way to determine if an underlying RSV infection is complicated by bacterial superinfection.^[22]

Prevention of RSV in older adults

JR: How is RSV transmitted?

AF: The transmission of RSV involves a combination of fomite transmission and droplets rather than small-particle aerosols.^[23] The virus is contagious, spreading easily from person to person. Epidemiological studies show that RSV infections peak first in young children and subsequently in adults, suggesting that transmission from children to older people is common.^[24]

JR: How can transmission of RSV be prevented?

AF: The use of masks and other simple preventative health measures such as handwashing effectively reduces the spread of all respiratory viruses.^[25] As health restrictions associated with the SARS-CoV-2 pandemic have eased, behaviours such as abandoning masks and returning to socialisation may be contributing to the current resurgence of other respiratory viruses like RSV.

In the US, many older people with underlying medical conditions are still using preventative measures such as masks. This is particularly valuable when community transmission of RSV or influenza is high.

JS: Here in the Philippines, mask mandates are no longer in place but many people within the population continue to wear masks in public places, and this is limiting the spread of respiratory viruses such as RSV. Other valuable infection control measures are still common, including thorough handwashing, the use of disinfectants, and sensible coughing and spitting etiquette.

We advise people with symptoms of upper respiratory infection to limit exposure to public or crowded places, or at least to wear a mask when such outings are unavoidable. Public health guidance should continue to focus on educating the general public on these simple behaviours, both to protect themselves and to reduce community spread of respiratory pathogens.

YL: The comprehensive and stringent measures implemented by China at the onset of the COVID-19 pandemic have had a lasting impact on public behaviour around personal hygiene and infection control over the last three years. These interventions have become ingrained in the public consciousness and have persisted long after official mandates have been lifted. People here voluntarily opted to wear masks during a recent flu outbreak, for example.

JR: What challenges do you anticipate in your region when the RSV vaccine becomes available?

YL: The issue of vaccine affordability is a significant factor that could influence uptake rates of an RSV vaccine, as we have seen with the influenza vaccine in China. China has no national influenza vaccination program; it is available only in the private health sector. Uptake has been low because of cost implications, not because of concerns about the vaccine itself. Chinese people are generally in favour of vaccination; the uptake of COVID vaccines has been high.^[26]

Given that RSV is a significant health concern, particularly in vulnerable populations like infants and the elderly, it would be important to make an RSV vaccine more accessible and more affordable.

JS: It is likely that RSV vaccination will focus initially on the paediatric population, as epidemiological data on susceptibility to severe RSV-associated illness in infants is so strong. This has been the case with other similar vaccines such as the pneumococcal conjugate vaccine aimed at preventing invasive pneumococcal disease.

Extending RSV vaccination to other high-risk groups, such as older adults with significant comorbidities or those who are immunocompromised, would be the logical next step once sufficient data and guidelines are available.

However, the issue of cost will also be a significant determinant of vaccine uptake in the Philippines. Delivering the RSV vaccine with other routine vaccinations like influenza and pneumococcal vaccines could enhance uptake rates, reduce costs, and offer comprehensive protection.

AF: RSV is recognised as a major paediatric pathogen and the development of maternal vaccines, a paediatric RSV vaccine, and anti-RSV monoclonal antibodies finally gives us good tools to prevent severe RSV infection in babies. These measures are acceptable to insurers because of the strong evidence of benefit in this population.

We currently have two RSV vaccines approved for older adults, with more on the way. Discussion with healthcare providers will be necessary to decide who is most at risk of severe RSV infection. Data on the anticipated benefits of vaccination is strong for adults over 75, particularly those with a high degree of frailty or who live in a long-term care facility. This group, together with adults over 65 with underlying cardiovascular or pulmonary conditions, could be key target populations for RSV vaccination.

Summary

The medical community often underestimates the burden of Respiratory Syncytial Virus (RSV) in older adults, overshadowed by the prominence of influenza despite substantial evidence of RSV's prevalence and impact. Several studies in the United States reported incidence rates of RSV in the elderly that were almost twice as high as those for influenza A, and RSV infection showed a high severity of the disease in this population.^[27,28] In the winter season, RSV infection can be responsible for a significant excess mortality along with the influenza virus.^[29]

Seasonal patterns contribute to its spread, with damper or colder conditions heightening transmission risks. In countries with temperate climates, RSV circulates during the winter season and peaks between December and February in the Northern Hemisphere, and between June and August in the Southern Hemisphere. In tropical countries, RSV outbreaks still occur during the warm, humid, and rainy days of the summer season.^[10]

In the elderly, RSV can lead to severe respiratory complications and exacerbate underlying conditions like cardiovascular diseases, necessitating sensitive and precise PCR testing for accurate diagnosis due to its clinical presentation similar to other respiratory infections. The introduction of the RSV vaccines presents a promising avenue for prevention, especially for high-risk populations because of age or underlying health status, though its success will depend on accessibility based on strategic prioritization and affordability. It is imperative to increase healthcare provider education on RSV infections and integrate vaccination into healthcare protocols to protect vulnerable populations effectively.

Acknowledgement: Dr Kathryn Senior, independent medical writer, helped draft this article.

Funded through sponsorship by Pfizer Private Limited. Medscape approached Pfizer Private Limited to fund the production of this editorial article. Pfizer Private Limited has had no influence over the selection of the authors or the content of the article and has reviewed it for technical accuracy only. The sponsorship fee included an honorarium for the authors, who were contracted and paid by Medscape Editorial. The views and opinions of the authors are not necessarily those of Pfizer Private Limited, or of Medscape, its publisher, advisers, or advertisers, all of which disclaim all and every liability and/or claims in this regard. No part of this publication may be reproduced in any form without the permission of the publisher.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.