FormalPara Key Summary Points

Respiratory syncytial virus (RSV) is a common, highly contagious pathogen and a leading cause of serious illness among vulnerable groups, such as infants and older adults.

While existing scientific evidence has predominantly focused on the epidemiology and disease burden of RSV in infants, data in older adults remain limited, particularly in Southeast Asia (SEA) and the Middle East and North Africa (MENA) region. Here, we outline the key challenges for understanding the burden of RSV in older adults in SEA and the MENA region.

A key challenge identified by the expert group, particularly in older adults, is a lack of awareness (among healthcare professionals, policy makers, and the public) of RSV burden and the associated risks for severe outcomes.

To address this, we advocate for medical education initiatives to increase awareness of RSV, increased testing and surveillance studies to better understand the burden of RSV, and, in the absence of current surveillance data in these regions, we propose extrapolating existing global and local pediatric data to inform the likely burden of RSV in older adults.

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Introduction

Respiratory syncytial virus (RSV) is a common and highly contagious respiratory pathogen. In vulnerable groups such as infants, young children, and older adults, RSV is a leading cause of serious respiratory disease which can lead to hospitalization and, in some cases, can be fatal [1, 2]. While existing literature has predominantly focused on the epidemiology and disease burden of RSV in the pediatric population [3], RSV is gaining recognition as an important respiratory virus in older adults, where it contributes to a high risk of severe complications requiring costly treatments, and greater hospitalization and mortality rates [4,5,6,7,8,9].

Older adults are particularly vulnerable to experiencing severe RSV disease due to variables such as waning immunity [10], aging of the lung [11], and high comorbidity rates (i.e., with chronic obstructive pulmonary disease [COPD], asthma, cardiovascular disease, and diabetes) [12,13,14,15,16,17,18]. In 2019, global age-standardized mortality rates for RSV in adults > 70 years exceeded that reported for children < 5 years [2]. As the global population ages, with the number of adults aged ≥ 60 years projected to reach 2.1 billion by 2050 [19], the public health burden of RSV is likely to continue to worsen. Because of this, it is imperative to undertake efforts to improve our understanding of the burden of RSV in older adults.

In 2023, two RSV vaccines were granted approval by the US Food and Drug Association and the European Medicines Agency, for the prevention of lower respiratory tract disease (LRTD) caused by RSV in adults aged ≥ 60 years, as recommended by the Advisory Committee on Immunization Practices (ACIP) [20,21,22]. This marked a turning point in the fight against RSV, allowing older adults (≥ 60 years) to be protected from RSV disease for the first time, as there had previously been no effective preventative or therapeutic options for RSV in this patient population. The ACIP also recently recognized the risk of severe RSV disease in individuals with underlying health conditions, and the Global Initiative for Chronic Obstructive Lung Disease has further recommended RSV vaccination among older adults with chronic heart or lung disease [20, 23].

Although systematic reviews have highlighted the burden of RSV in older adults in the USA, and some European and Asian countries, limited epidemiological data exist in regions with poor RSV surveillance, notably in Southeast Asia (SEA) and in the Middle East and North Africa (MENA) region [4, 6, 13, 24,25,26]. Consequently, the burden of RSV in these regions is poorly understood. Data that are available in these regions largely focuses on the pediatric population, meaning understanding of RSV burden is particular poor for older adults, who make up an increasing proportion of the population [27, 28]. Furthermore, in SEA and the MENA region, a particularly high incidence of LRTDs has been reported, suggesting that there may be a high burden of respiratory infections, including RSV [29].

Here, we outline the key challenges for understanding the burden of RSV in older adults in SEA and the MENA region and make suggestions that we believe will help to improve awareness of RSV within this vulnerable population.

This article is based on previously conducted research and does not contain any new studies with human participants or animals performed by any of the authors.

Lack of Awareness of RSV and Associated Risks for Severe Outcomes

A key challenge in SEA and the MENA region is the limited awareness of RSV as a potential cause of respiratory illness in older adults. A global survey revealed that in certain countries, including three from SEA and the MENA region, the majority of healthcare professionals and researchers/scientists perceived local awareness of RSV to be low (agreed by 54.8% of respondents) and found that RSV is not considered a priority public health issue (agreed by 83.8% of respondents; Fig. 1) [30]. This is despite RSV infections being shown to cause severe morbidity and mortality, as demonstrated by several studies from Thailand (Table 1). As human behavior is a fundamental factor influencing RSV transmission, raising awareness of RSV and its associated health risks is integral to reducing the burden of RSV in these regions [31].

Fig. 1
figure 1

Epidemiology and challenges associated with understanding the burden of RSV in older adults in SEA and the MENA region. Data are reported from [2, 3, 12, 17, 25, 26, 30, 33, 37, 39, 40, 53, 62, 69, 70, 74, 81, 82, 86]. CAP community-acquired pneumonia, COVID-19 coronavirus disease 2019, ICU intensive care unit, RSV respiratory syncytial virus, RT-PCR reverse transcription polymerase chain reaction

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Table 1 RSV-related morbidity and mortality outcomes in older adults in SEA and the MENA region
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Following the relaxation of coronavirus disease 2019 (COVID-19) pandemic mitigation measures, many areas of the world experienced an off-season resurgence of RSV cases, which varied in intensity and clinical severity [32,33,34,35]. For example, one US community-based cohort study reported a post-COVID-19, off-season resurgence of RSV-positive acute respiratory infection in older adults [36]. Resurgences of RSV were also reported in countries in the MENA region. In Egypt, there was an increase in the rate of RSV infections in children from 15% (2020–2021) to 70% by the end of 2022, with the incidence and severity of RSV infections exceeding that of influenza [33]. Unfortunately, data for older adults were not captured. In Turkey, between October 2022 and February 2023, the Ministry of Health reported that RSV was the most common respiratory isolate detected in both pediatric and older adult patients hospitalized with severe acute respiratory infection [37]. Furthermore, in Iran in 2022, the first outbreak of RSV since the beginning of the COVID-19 pandemic was reported, with approximately 53% of hospital inpatients aged 1 month–5 years (N = 30) being diagnosed with RSV infection, contrasting with no diagnoses of influenza or SARS-CoV-2 infection [32]. Finally, Qatar experienced an earlier onset of the typical RSV season in late summer of 2021, which was hypothesized to be a result of the relaxation of international travel restrictions [38].

A recent high incidence and severity of RSV was also reported in Thailand. From January to September 2023, an active surveillance study of patients of all ages with acute respiratory tract infection across six hospitals was conducted by the Ministry of Public Health Thailand in collaboration with the US Centers for Disease Control and Prevention (CDC). This study found that, of 5110 samples, 270 were confirmed as RSV via reverse transcription polymerase chain reaction (RT-PCR) [39]. Of these, 73% resulted in hospitalization and 9% required intensive care unit (ICU) admission, with one death reported in an adult aged 86 years with comorbidities.

While the COVID-19 pandemic has led to recent off-season resurgences of RSV, it has also increased awareness of the potential for severe respiratory viral infections among older adults [40, 41]. In multiple countries, including Bahrain and Saudi Arabia, RSV is now classed as a mandatory notifiable disease, meaning that all infections must be reported, regardless of patient age [42, 43]. In Europe, discussions are ongoing for the inclusion of RSV on the list of notifiable diseases [44]. Considering these reports, we believe that there is now a global momentum to increase awareness of RSV, and available vaccines, in older adults amongst healthcare professionals, policy makers, and the public.

Although awareness of RSV in older adults may be slowly increasing in SEA and the MENA region following the COVID-19 pandemic, comprehensive local epidemiological data are still lacking, particularly in older adults. According to the 2019 Lancet Global Burden of Disease (GBD) study, in the MENA region, the most attributable deaths for RSV were among people aged ≥ 80 years, followed by those aged < 5 years [45]. Several reports across SEA also suggest that RSV forms a notable proportion of hospitalizations for respiratory illness and pneumonia amongst older adults in this region [46,47,48]. This trend extends globally, where the burden of RSV is particularly high in older adults, and in those with underlying health conditions [4,5,6,7, 9, 49,50,51,52]. For example, in a retrospective study of patients with community-acquired pneumonia due to RSV admitted to one hospital in Saudi Arabia between 2016 and 2019, the majority of patients requiring hospitalization were elderly with multiple comorbidities, with 23.8% of patients requiring ICU admission [53]. Similarly, of the 850 patients aged between 3 days and 80 years hospitalized with respiratory tract infections between 2010 and 2014 in one hospital in Kuwait, RSV was the third most detected virus [54].

Data from two systematic literature reviews covering the MENA region suggest that RSV is a common cause of respiratory tract infections in children and can cause a significant burden of disease [25, 26]. We therefore recommend extrapolating available pediatric data to help further understanding of the risks of RSV infections in older adults in the region. Additionally, as epidemiological trends of RSV in pediatric populations are similar between the USA and Europe, we can also leverage data on older adults from these countries to inform on the likely burden of RSV disease in older adults in SEA and the MENA region. We also recommend drawing parallels to other respiratory infections, such as influenza, which is similar to RSV with respect to clinical manifestations and outcomes of infection [8].

It is also important to emphasize the potential transmission of infection between infants and children, and older adults within communities in SEA and the MENA region. Household crowding has been shown to favor increased transmission of respiratory viruses such as RSV and also to increase the potential for severe disease [55, 56]. This is of particular concern in SEA, which is one of the most densely populated regions in the world [57, 58]. Here, there is increased potential for RSV to spread between children and older adults, who may live in close proximity. A previous US study found that children may be a significant source of RSV transmission to older adults, with peak RSV incidence in older adults occurring a few weeks after overall peak RSV occurrence [59]. It is imperative that physicians operating in densely populated countries within SEA and the MENA region raise awareness of the increased risk of RSV to older adults within this context. To achieve this, we suggest utilizing learnings from the COVID-19 pandemic, where high rates of intra-family transmission were also recorded (Table 2) [60, 61].

Table 2 Key actions to raise awareness and improve understanding of RSV burden in SEA and the MENA region
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Underdiagnosis

Underdiagnosis of RSV within SEA and the MENA region poses a significant challenge for understanding its burden. Unlike infants presenting with LRTD, the symptoms of RSV infection in older adults are nonspecific, variable, and may be indistinguishable from those of other respiratory infections (Fig. 1) [62]. Additionally, RSV coinfection with other respiratory tract pathogens is common, presenting mixed clinical features that are difficult to distinguish [25]. It is also possible that RSV coinfection could occur with COVID-19, although preliminary research suggests that viral coinfections with COVID-19 are less common as a result of viral interference [63]. Bacterial coinfections with RSV are also common, with one US study reporting evidence of concomitant infection in 31% of hospitalized patients with RSV [64]. These challenges can make it difficult to identify RSV and underscore the need for diagnostic tests to accurately estimate the burden of disease. A summary of identified studies where RSV testing was completed is provided in Supplementary Material Table 1, which highlights that many studies lack adult patients or stratification by age, with many also being conducted exclusively in patients with additional respiratory illnesses.

Diagnostic testing for RSV and other respiratory viruses (with the exception of COVID-19 and influenza) is not routinely performed in both adults and children in SEA and the MENA region. This is likely in part due to there being limited treatment options for RSV infection [65]. In many cases, the decision to test for these viruses will depend on a physician’s level of suspicion for infection and on disease severity [26]. Consequently, testing may only be performed upon suspicion of severe RSV that requires hospitalization. In a systematic review of RSV epidemiology in the MENA region, 89% of the identified studies (n = 47) were conducted in hospital settings, highlighting this as a common route for RSV detection [26]. Given the low awareness of RSV infection in older adults, there is reason to believe that suspicion for infection and therefore testing is particularly low amongst this age group in SEA and the MENA region. This is also true for developed countries, such as Germany, where RSV diagnostic testing is not routinely performed in adults presenting with respiratory symptoms [9].

The underdiagnosis of RSV may also be influenced by healthcare infrastructure and socioeconomic barriers, particularly in regions with varying access to accurate diagnostic tests and to laboratories for RSV screening. The American National RSV Surveillance Data has shown that access to a laboratory for RSV screening is the major contributor to RSV reporting during different seasons [25, 66]. However, across SEA and the MENA region, access to such facilities and to tests capable of accurately diagnosing RSV is likely to be variable. For instance, although the gold standard of RSV detection is RT-PCR analysis [67, 68], use of RT-PCR in these regions is often limited to patients hospitalized with RSV because of high associated costs.

For example, in the Philippines, testing for RSV infection is mostly limited to private healthcare centers, where it is available to patients out-of-pocket. Additionally, in Thailand, rapid multiplex PCR-based testing is not routinely used because of its relatively high cost compared to antigen testing (100 US dollars per PCR test vs 10–15 US dollars per antigen test) (Fig. 1) [69]. Several diagnostic tests that are available in SEA and the MENA region are also limited by their inability to detect multiple viruses, including RSV, in cases of co-infection [15].

A systematic review of RSV epidemiology in the MENA region revealed that while the majority of studies utilized RT-PCR, many also employed rapid diagnostic tests (Fig. 1) [26]. Such diagnostic tests are known to be less sensitive than RT-PCR (83% and 86% vs multiplex RT-PCR for direct fluorescent antibody and viral culture, respectively) [70]. Moreover, as older adults shed RSV at considerably lower viral titers than infants, the ability to detect RSV using these tests is likely to be even lower [71]. Additionally, the use of nasopharyngeal samples only is known to occasionally produce false negative results for RSV infections in adults because of the short duration of viral shedding from the upper respiratory tract [72]. Despite these limitations, rapid diagnostic tests can be considered as a more accessible alternative to RT-PCR, although costs and necessity should be considered. The increased availability of rapid, PCR-based point-of-care testing could therefore promote accurate diagnosis and improved awareness of RSV and other respiratory viruses, and be used for future surveillance research in resource-constrained settings [73].

It is evident that underdiagnosis must be recognized as a multifaceted challenge. To address the challenge of RSV underdiagnosis and awareness in SEA and the MENA region, we propose a proactive approach to increase awareness amongst local physicians attending to geriatric and specialists attending to high-risk patients (e.g., pulmonologist and cardiologists) about the burden of RSV in older adults. Despite the current challenges, we find reason for optimism following recent shifts in attitudes toward routine testing for RSV. Notably, changes in perceptions have been observed in Turkey, where RSV infections have recently been recognized as a priority in pediatric populations [37]. This needs to extend to the older adults who, as we have discussed in this paper, suffer from more severe, debilitating, and often comorbid disease with RSV. By educating healthcare professionals on the burden of disease in their region and country through medical events and education materials (Table 2) we can foster a greater understanding of RSV and facilitate improvements in diagnostics, better-informed public health strategies, and ultimately enhance care for older adults.

Surveillance and Reporting Challenges

In many regions of the world, including in SEA and the MENA region, surveillance for RSV is limited [74]. As such, estimations of the prevalence of RSV infections can vary widely. According to a systematic literature review conducted in the MENA region, between 2001 and 2017, the annual rate of prevalence of RSV amongst respiratory infections varied from 1.8% in Oman (during 2011–2012) to 64.0% in Jordan (during 2006–2007) (Fig. 1) [25].

Where RSV is not a mandatory notifiable disease, cases are likely to be highly underreported. Moreover, even in cases where reporting is mandatory, specific surveillance efforts for RSV are often lacking. The Global Epidemiology of RSV (GERi) network, including data from Vietnam and Singapore, identified the greatest burden of disease among those aged < 1 year old, but highlighted a lack of surveillance data in older adults (Fig. 1) [3].

Scarcity of data and inconsistent reporting of RSV cases across healthcare settings poses significant challenges in obtaining comprehensive and accurate epidemiological data in SEA and the MENA region. This is particularly pertinent concerning data in older adults. A systematic review on RSV epidemiology in the MENA region identified 90 studies, the majority of which were conducted in children, with 83% of these articles only including children aged < 3 years [26]. Similarly, in the Philippines, a study of the surveillance of respiratory viruses (including RSV) found that the majority (75.6%) of cases sampled were children < 5 years [75].

Additionally, RSV infection rates have clear seasonality, with a global trend over the winter months [76]. In the MENA region, the RSV outbreaks generally occur during October–May [26]. In SEA, although outbreaks are most common during the hot and rainy season, they occur throughout the year, with variability in seasonality reported between countries [15]. However, this seasonality is not consistently accounted for in studies focusing on older adults in SEA and the MENA region, leading to variability and potential for bias in reported data [13, 15]. Further data on the seasonality of RSV within older adults in SEA and the MENA region is therefore required to accurately assess the burden of RSV in this population.

In many regions, surveillance efforts for RSV infections may be secondary to existing influenza surveillance systems (Fig. 1). For example, in community care in Singapore, only respiratory samples that first test negative for influenza are then tested for RSV and other respiratory viruses [3]. In Thailand, FLU Vaccine Effectiveness (FLU-VE) is an active influenza sentinel program overseen by the Ministry of Public Health Thailand, with collaboration from the US CDC [39, 77]. This program monitors influenza cases amongst people with symptoms of influenza-like illness who visit one of seven hospitals within the region. Although the focus is on detecting influenza, other respiratory infections, such as RSV, are also recorded. A similar program is operational in Turkey, overseen by the Turkish Public Health Agency of Department of Infectious Diseases [37].

To advocate for increased surveillance of RSV infection in SEA and the MENA region, it will be important to leverage existing data highlighting the burden of RSV in comparison with respiratory viruses such as influenza, for which there is already good surveillance. According to the 2016 Lancet GBD study, which captured data from 195 countries including some across SEA and the MENA region, RSV and influenza were responsible for 3.2% (95% uncertainty interval [UI] 2.3–4.4) and 2.5% (1.9–3.1) of deaths due to lower respiratory infection, respectively [78]. These findings align with data from the USA: adults hospitalized with RSV infections were found to experience longer hospital stays and more complications compared with influenza cases [79]. Amongst hospitalized adults aged ≥ 60 years whose data were captured as part of the US Investigating Respiratory Viruses in the Acutely Ill (IVY) Network, RSV was less common than COVID-19 or influenza, but was associated with more severe disease [80].

We hope that as awareness of RSV increases, surveillance studies, which account for seasonality of RSV, may be undertaken to allow for better estimations of RSV prevalence and disease burden across different countries within these regions (Table 2). Together, these data will be imperative in addressing the surveillance and reporting challenges associated with RSV in older adults in SEA and the MENA region. This may raise awareness of RSV and help to recognize the need for increased testing and for the introduction of routine, accessible vaccination against RSV in older adults, when available. Ultimately, these efforts hope to reduce the burden of RSV in these vulnerable populations.

Complexity of Comorbidities

The presence of pulmonary and cardiovascular comorbidities is known to increase the risk of severe RSV disease, particularly in older adults who often present with a greater number of underlying conditions such as COPD, asthma, cardiovascular disease, and diabetes (Fig. 1) [12,13,14,15,16,17]. For example, in Saudia Arabia, of the 80 adult patients hospitalized between 2016 and 2019 with community acquired pneumonia due to RSV in one hospital, a high proportion had comorbidities, including hypertension (65.0%), diabetes (58.8%), chronic respiratory disease (52.5%), and heart failure (38.8%) (Fig. 1) [53]. A summary of RSV-related morbidity and mortality outcomes in older adults with underlying health conditions is provided in Table 3.

Table 3 RSV-related morbidity and mortality outcomes in older adults with underlying health conditions
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In SEA and the MENA region, there is a notably high prevalence of chronic conditions that increase the severity of RSV disease (Fig. 1). For example, data from the 2019 Lancet GBD study highlighted that the age-standardized prevalence (per 100,000 population) of asthma (MENA: 3819.3 [95% UI 3262.5–4512.7]; SEA: (3431.8 [2926.7–4059.8]) and heart failure (MENA: 784.4 [628.3–976.8]; SEA: 756.0 [604.9–946.2]) was greater in these regions than observed globally (3415.5 [2898.9–4066.2] and 711.9 [591.2–858.3], respectively) [81, 82]. Additionally, although overall prevalence of COPD in SEA and the MENA region is lower than that observed globally (2638.2 [2492.2–2796.1]), a particularly high prevalence was reported in Myanmar (3963.7 [3825.4–4096.7) and Turkey (3287.1 [3187.4–3380.3]) [83]. There is also a high prevalence of tobacco smoking, particularly in SEA, which has been shown to contribute to the severity of RSV infections by enhancing RSV-induced pulmonary inflammation [84]. The age-standardized prevalence of tobacco smoking amongst male individuals aged ≥ 15 years was 48.2% (95% UI 47.5–48.9) in SEA versus 32.7% (32.3–33.0) globally [85].

As a result of immune decline with older age, RSV infections can exacerbate underlying conditions, such as asthma and COPD, and contribute to increased rates of morbidity and mortality in older adults (Fig. 1) [13, 17, 86, 87]. In patients with acute heart failure and patients experiencing exacerbations of COPD and asthma, it can also be difficult to identify RSV infections as a result of the masking and/or overlapping of clinical symptoms [88]. This is confounded further by a low level of suspicion for RSV infection amongst these patients. Currently, testing for RSV in cardiopulmonary exacerbations is not routine practice in SEA and the MENA region [17]. Instead, only well-known respiratory viruses such as influenza or COVID-19, and bacteria such as pneumococcus may be tested for in these patients. However, the clinical illness caused by RSV in elderly adults may be nonspecific and indistinguishable from some respiratory viruses [62]. These challenges complicate defining causality and estimating morbidity associated with RSV.

We advocate for routine testing for RSV in older adults with underlying conditions, especially in cases of disease exacerbation, to enable improved understanding and assessment of the role of respiratory viruses in severe disease. To achieve this change, existing physician knowledge should be leveraged around respiratory infections (e.g., influenza, COVID-19, and pneumococcal disease) that may already be routinely tested for and vaccinated against in patients with these underlying conditions.

However, it must be acknowledged that awareness of RSV infection in older adults, including those with underlying health conditions, is evolving globally. The American Heart Association and the recent 2024 GOLD report acknowledge the US CDC Advisory Committee on Immunization Practices’ and European Commission recommendations for RSV vaccination in individuals aged ≥ 60 years and/or with chronic heart or lung disease [23, 89]. The American Diabetes Association also acknowledges this recommendation for individuals aged ≥ 60 years with diabetes [90]. In the USA, recent estimates for RSV vaccination coverage among adults with chronic health conditions were 21.4% [91]. We believe that such recommendations, as well as incorporating vaccine assessment into routine clinical care, may foster increased awareness of and testing for RSV in these patients. This will ultimately position RSV as an important respiratory virus alongside others such as influenza, COVID-19, and rhinoviruses in SEA and the MENA region.

To help achieve this goal, research conducted in hospital settings is needed to compare morbidity and mortality associated with RSV and other respiratory viruses in older adults with underlying conditions (Table 2). Ultimately, efforts to improve testing for RSV in these vulnerable populations may offer the potential for RSV vaccination to be integrated into existing immunization programs focusing on older adults.

Conclusion

Understanding the burden of RSV in older adults and in individuals with underlying conditions within SEA and the MENA region is complex. Challenges include a lack of awareness of RSV infections and the associated risks for severe outcomes, especially considering underdiagnosis, surveillance limitations, and the complexities of comorbidities. This lack of awareness is not a problem limited to healthcare professionals but also patients and health authorities. Addressing these concerns will first require an improved awareness amongst physicians of the need to protect older adults from potentially life-threatening RSV infections, paving the way for routine testing and vaccination in this demographic. Moreover, we advocate for surveillance studies across SEA and the MENA region that will provide comprehensive and accurate epidemiological data and highlight the underreported burden of disease, particularly among the most vulnerable populations.