Respiratory syncytial virus (RSV) infections in adults: Current trends and recommendations for prevention – a global challenge from a local perspective

ABSTRACT

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LRTI) and a major health threat especially for children and older adults. Epidemiological data reveal that RSV-associated global mortality rates in individuals aged ≥ 70 years exceeded those in children aged < 5 years in 2019. Although effective interventions have decreased RSV-related deaths in children aged < 5 years over time, RSV appears increasingly significant issue for the elderly and adults with underlying health conditions. Furthermore, there is currently no specific treatment for RSV infections in adults, highlighting the importance of prevention. Recently, three vaccines (RSVPreF3, RSVpreF, and mRNA-1345) have been approved for adults to date. In this article, we aimed to review the characteristics of RSV infections in adults and the evidence on the safety and efficacy of RSV vaccines, with a glimpse of the current situation in Türkiye- one of the low- and middle- income countries (LMICs).

Plain Language Summary

Respiratory syncytial virus (RSV) is a virus that can cause serious lung infections. It has long been considered as a child illness; however, RSV can cause serious illness in older people and in people with long-term health problems like heart or lung disease. Among the high-risk adults, RSV can result in severe diseases, hospitalizations, and even death. Today, there is no cure for RSV in adults, so prevention is the cornerstone of protecting people at risk. Three vaccines have been approved that can protect older people and people with chronic medical conditions. This review article provides information on the characteristics of RSV infections in adults, available RSV vaccines and their role in preventing RSV. Adding the available vaccines against RSV to regular adult vaccination programs can save lives, keep people out of the hospital, and protect older adults and those with long-term health problems.

Introduction

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LRTI) and a major health threat especially for children and older adults.¹ RSV usually causes seasonal epidemics, with outbreaks generally occurring between October and May in the Northern Hemisphere and between May and September in the Southern Hemisphere.² The relationship between RSV epidemics and seasonality may vary across years and geographic locations.³ During the first two years of the COVID-19 pandemic, RSV circulation declined significantly due to widespread use of infection prevention measures; however, RSV reemerged during the off-season when these measures were gradually reduced.⁴

RSV infections are the leading cause of respiratory tract infection-related hospitalizations in children <5 years of age.¹ In healthy adults, RSV infection can manifest with mild symptoms in the form of a common cold. However, it can present with acute cardiovascular and severe respiratory conditions in the elderly and other vulnerable groups.^1,5 The major conditions that increase the risk of severe RSV in adults have been reported by the United States Centers for Disease Control and Prevention (US CDC).⁶ These conditions include cardiovascular disease (heart failure, coronary artery disease, congenital heart disease), chronic respiratory disease (chronic obstructive pulmonary disease [COPD], emphysema, asthma, interstitial lung disease, cystic fibrosis), renal disease (end-stage renal disease, dependence on hemodialysis or other renal replacement therapy), diabetes mellitus (complicated by end-organ damage, requiring treatment with insulin or sodium-glucose cotransporter-2 (SGLT2) inhibitor), neuromuscular conditions (poststroke dysphagia, amyotrophic lateral sclerosis, muscular dystrophy), chronic liver disease (cirrhosis), chronic hematologic conditions (sickle cell disease, thalassemia), severe obesity (body mass index ≥40 kg/m²), moderate or severe immune compromise (malignancies, immunosuppressive therapy, advanced human immunodeficiency virus [HIV] infection, active treatment with high-dose corticosteroids), frailty, residence in a nursing home, residence in a remote or rural community. While these general risk factors serve as a basis, countries need to identify the risk factors in relation to their specific conditions.⁶

According to the data from the Global Burden of Disease study, the total number of deaths due to RSV infection worldwide is 338,495 in 2019, compared to 76,000 in 2016.⁷ Additionally, the mortality rate in the elderly aged >70 years was reported to exceed the mortality rate in children aged <5 years in 2019.⁷ While successful interventions in children <5 years of age have reduced RSV-related childhood deaths over the years, RSV appears to be a growing problem for the elderly and adults with comorbidities.⁷ The burden of RSV in older adults is similar to that of influenza, and the two infections are comparable in terms of hospitalization and mortality rates.⁸ In a recent study in older adults, the rate of pneumonia, hospitalization rates, intensive care unit admissions, and length of stay were significantly higher in the RSV group than in the influenza group, while mortality rates on the 30^th day were similar (RSV: 9.6%, Influenza: 9.7%; p = .973).⁹ RSV is a major cause of death in people aged ≥65 years; in some seasons, it is associated with more deaths as compared with influenza.¹⁰ Most RSV-associated deaths (>70%) in older adults occur in low- and middle-income countries (LMICs).¹¹

There is currently no specific treatment for RSV infections in adults, highlighting the importance of prevention. The recent introduction of effective RSV vaccines for adults and the opportunity of protection from infection encourages efforts to raise awareness on the RSV infection in the medical society.¹² Accordingly, we aimed to review the characteristics of RSV infections in adults and the evidence on the safety and efficacy of RSV vaccines, with a glimpse of the current situation in Türkiye- one of the LMICs.

Epidemiology

Epidemiological data on the RSV in adults and elderly are evolving with the advent and wider use of molecular diagnostic techniques and cases once deemed as influenza like illness (ILI) have been diagnosed as RSV in the recent years.¹³ Thus, the true picture of RSV epidemiology has begun to emerge and RSV infections among older adults have started to attract more attention.^13,14 The increased use of diagnostic tests due to the COVID-19 pandemic also revealed that RSV cases were not sufficiently detected in pre-pandemic seasons. It has been suggested that RSV was up to seven times under-detected in individuals over the age of 60 in the pre-pandemic period.¹⁵ RSV incidence rates ranged widely among studies and that the incidence of RSV infection in older adults was often underestimated due to various limitations in the methodology of the studies.¹⁶ Available data indicate that the annual RSV attack rate ranges from 1% to 7% in the general adult population, and from approximately 4% to 10% among the elderly and high-risk groups.¹⁷ In high-income countries (HICs), RSV infections in older people are projected to reach 10 million cases, 800,000 hospitalizations, and 74,000 in-hospital deaths by 2025.¹⁸ A significant portion of the global RSV burden is concentrated in LMICs; however, epidemiological data on RSV in adults in LMICs remain very limited.¹¹ In Latin America, it has been reported that awareness is low, testing rates are limited, and diagnoses are often missed among older adults and adults with underlying health conditions, resulting in inadequate data on the epidemiology of RSV.¹⁹ It has been reported that published epidemiological data on RSV infections among older adults in Taiwan is scarce. However, the growing proportion of older adults is anticipated to increase the burden of RSV infections. Therefore, generating epidemiological data should be prioritized to develop preventive strategies.²⁰ Similarly, epidemiological data on adult RSV infections in the Middle East and North Africa (MENA) region are limited. It has been reported that, there is a need for further prospective surveillance studies to better understand the burden and dynamics of RSV in this population.²¹

In Türkiye, influenza-like illness (ILI) surveillance was initiated by the Ministry of Health in 2004.²² COVID-19 pandemic led many countries to expand their existing surveillance systems to include other viruses or to develop new systems. Similarly, in Türkiye, other respiratory viruses have been integrated into sentinel surveillance over time. Sentinel ILI surveillance is conducted with 250 family physicians in 23 provinces selected from different regions of Türkiye, while sentinel severe acute respiratory infection (SARI) surveillance is carried out with 11 designated hospitals in 8 selected provinces (Figure 1). As part of the surveillance, multiplex polymerase chain reaction (PCR) tests are performed on a specified number of individuals meeting the established case definitions. The results of these tests are analyzed and evaluated by the Ministry of Health for monitoring the epidemiology of the respiratory viral infections.²² According to data from ILI surveillance, among viral pathogen positive outpatient samples, Influenza and RSV positivity were 37.6% and 5.0%, respectively, in the 2023–2024 season, and 36.0% and 5.2% in 2024–2025 season. On the other hand, according to SARI surveillance data, RSV positivity rates were higher than influenza among hospitalized patients. Among viral pathogen positive samples, influenza and RSV positivity were 12.4% and 24.8%, respectively, in 2023–2024 season, and 19.0% and 30.9% in 2024–2025 season (Table 1).^22,23 Based on the data herein, it can be concluded that RSV, although varying by season, is a leading viral cause of SARI requiring hospitalization. Unfortunately, it is not possible to evaluate the age distribution of RSV positive cases in the national surveillance reports among the ILI and SARI cases overall; however, limited local studies from Türkiye provide data on adults and elderly. A study carried out among adult patients with viral respiratory infections visiting a university hospital over a 12-year period, the causative agent was detected in 336 patients, among which 181 (53.8%) were influenza viruses and 24 (7.1%) were RSV.²⁴ In another university hospital, of 42 respiratory samples from adult inpatients with respiratory infection symptoms, the causative agent was detected in 24 samples, being influenza viruses in 7 (29.7%) samples and RSV in 3 (12.5%) samples.²⁵ The causative agent was investigated in another study on respiratory samples of 140 adult patients with viral pneumonia and positivity was detected in 25 patients. Influenza viruses were detected in 12 (48.0%) and RSV was detected in 8 (32.0%) of them.²⁶ In a study conducted using two seasons’ data between November 1^st, 2022 and May 31^st, 2024 from Türkiye as part of the Global Influenza Hospital Surveillance Network project, multiplex PCR findings of swab samples (n = 969) from patients with ILI symptoms admitted to five hospitals were evaluated.²⁷ Among these samples, 724 were obtained from adult patients, and viral pathogens were detected in 73 (10.1%) of them. Among the positive samples, influenza was identified in 20 (27.4%) cases and RSV was identified in 17 (23.3%) cases.²⁷ Studies on RSV epidemiology in Türkiye are summarized in Table 1.

Figure 1.

(a) Sentinel influenza-like illness (ILI) surveillance regions (20 family physicians each in Istanbul and Ankara, 10 family physicians in each of other provinces; Adana, Antalya, Bursa, Diyarbakır, Edirne, Erzurum, Eskişehir, Hatay, İzmir, Kars, Kocaeli, Konya, Malatya, Muğla, Samsun, Sivas, Şanlıurfa, Tekirdağ, Trabzon, Uşak, Van); (b) Sentinel severe acute respiratory infection (SARI) surveillance regions: provinces and hospitals: Adana (Adana Seyhan State Hospital), Ankara (Ankara Training and Research Hospital, Health Sciences University Gülhane Training and Research Hospital), Erzurum (Erzurum City Hospital), Eskişehir (Eskişehir City Hospital), Istanbul (Istanbul Bakırköy Dr. Sadi Konuk Training and Research Hospital, Istanbul Kartal Dr. Lütfi Kırdar City Hospital), İzmir (Health Sciences University Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, Health Sciences University Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital), Samsun (Samsun Training and Research Hospital), Van (Health Sciences University Van Training and Research Hospital.

Table 1.

Studies on respiratory syncytial virus (RSV) epidemiology in Türkiye.

Year	Site	Population			Detection method	Viral positivity n (%)	Among viral pathogens n (%)		Reference
		Definition	Age	N			Influenza	RSV
2024–2025	ILI Surveillance	ILI defined by family physician	All ages	3394	Real‐Time PCR	1590 (46.8)	572 (36.0)	82 (5.2)	23
2024–2025	SARI Surveillance	Hospitalized SARI patients	All ages	2126	Real‐Time PCR	796 (37.4)	151 (19.0)	246 (30.9)	23
2023–2024	ILI Surveillance	ILI defined by family physician	All ages	5736	Real‐Time PCR	2172 (37.9)	816 (37.6)	109 (5.0)	22
2023–2024	SARI Surveillance	Hospitalized SARI patients	All ages	3537	Real‐Time PCR	1035 (29.3)	128 (12.4)	257 (24.8)	22
2022–2024	Ankara, 5 tertiary care academic hospitals	Inpatients with ILI symptoms	Adults	724	Multiplex PCR	73 (10.1)	20 (27.4)	17 (23.3)	27
2015–2018	Bursa, Uludag University Hospital	Inpatients with respiratory infection symptoms	Adults	42	Real‐Time PCR	24 (57.1)	7 (29.2)	3 (12.5)	25
2002–2014	Izmir, Ege University, Faculty of Medicine	Viral respiratory infections Outpatients/Inpatients	Adults	Outpatients: 434 Inpatients: 799	Cell culture, Multiplex PCR, DFA	Outpatients 152 (35.0) Inpatients 184 (23.0)	Outpatients 103 (67.8) Inpatients 78 (42.4)	Outpatients 1 (0.7) Inpatients 23 (12.5)	24
2010–2011	Konya Beyhekim State Hospital	Viral pneumonia in Outpatients/Inpatients	Adults	140	Multiplex PCR	25 (17.9)	12 (48.0)	8 (32.0)	26

Note: DFA, direct fluorescent antibody; ILI, influenza-like illness; PCR, polymerase chain reaction; RSV, respiratory syncytial virus SARI, severe acute respiratory infection.

Clinical presentation

RSV shows a wide spectrum of clinical presentations, ranging from asymptomatic infection to severe LRTI. The first symptoms usually appear following the 4–7-day incubation period after transmission. However, in asymptomatic cases or during the first two days before symptoms appear, individuals may be contagious.⁵ Reinfection is possible two months or more after natural infection with RSV.² Co-infection with other respiratory viruses may occur and may cause serious clinical effects, especially in older adults.²⁸ Co-infection with bacteria also causes increased mortality in elderly patients.²⁹

The clinical presentation of RSV in adults differs from that in children. RSV in children may present with initial symptoms such as nasal congestion, cough, and runny nose, followed by fever, wheezing, tachypnea, and apnea. Bronchiolitis, otitis, pneumonia, sepsis, and meningitis can also be seen in children.¹ In healthy adults, RSV usually presents as an upper respiratory tract infection with mild to moderate symptoms. In adults, fever rarely reaches > 38°C; cough occurs in over 90% and wheezing in about 40%.¹ However, RSV may be more severe in those with respiratory or cardiac comorbidities and in the elderly. Moreover, preexisting cardiovascular conditions are related to hospitalization in 45% to 63% of adults diagnosed with RSV.³⁰ Cardiovascular complications, including congestive heart failure exacerbation, acute coronary events, arrhythmia, stroke, and cerebrovascular events, have also been reported in 14% to 22% of adult patients hospitalized with respiratory disease due to RSV.³⁰ A prospective cohort study of healthy elderly patients (≥65 years of age) and high-risk adults (those with chronic heart or lung disease) examined respiratory diseases over four consecutive winters. Among those hospitalized in this cohort, RSV was associated with 11.4% of COPD exacerbations, 7.2% of asthma exacerbations, and 5.4% of congestive heart failure exacerbations.³¹

RSV infection leads to prolonged hospitalization in the elderly and in adults with comorbidities. A recent European study reported 92% of RSV-related hospitalizations in adults to be in patients aged ≥65 years.³² Besides, adults with chronic diseases are 3–28 times more likely to be hospitalized due to RSV compared to those without chronic diseases.³³ RSV-related hospitalization has been reported to increase with increasing age; hospitalization rate is higher in high-risk adults (with comorbidity) than in low-risk adults (ratio high/low risk: 2.7 for 18–49 years, 9.8 for 50–64 years, and 11.1 for 65–74 years age groups).³⁴ In a recent study, nearly 25% of adults aged ≥50 years (n = 6248) hospitalized for RSV infection developed acute cardiac complications, with 8.5% of these cases having no prior documented cardiovascular disease; these complications were then further associated with worse outcomes.³⁵ The in-hospital mortality rate associated with RSV has been reported to range between 4% and 18%,^17,36,37 while in the intensive care unit, the mortality rate can reach up to 40%.¹⁷

Diagnosis

It is difficult to differentiate RSV from influenza and other respiratory viral infections by clinical presentation per se. However, it has been reported that patients with RSV often present with nasal congestion, productive cough, and wheezing, while sudden onset of symptoms, fever and gastrointestinal symptoms are more common in influenza.^38,39 Radiographic signs of RSV pneumonia – such as localized or widespread interstitial or ground-glass pulmonary opacities, thickening of bronchial walls, tree-in-bud patterns, and lobar consolidation – may also resemble those of other viral infections.²

Methods used for definitive diagnosis of RSV infection include culture, detection of RSV antigen, positive acute viral serology, and molecular methods. Molecular methods are preferred in diagnosis of RSV due to their high sensitivity, high specificity, and rapid response within hours.^2,38 Real-time PCR (RT-PCR), especially the singleplex test, is the most sensitive RSV diagnostic test in adults.^40,41

There are some challenges that make laboratory diagnosis of RSV difficult. Multiplex PCR is preferred in routine practice because it allows multiple viruses to be tested simultaneously. This method is also used in routine practice in Türkiye. However, when singleplex PCR is used as a reference test, the sensitivity of multiplex PCR is reported to be 93%.⁴¹ In fact, in a study using only adult samples, the sensitivity of multiplex PCR was found to be 81%, pointing out to the possibility of underdiagnosis due to false negativity.⁴¹ The sensitivity of diagnostic tests primarily depends on the viral load and thus depends on the patient’s age, disease severity, and quality and timing of sample collection. RSV infections are more difficult to diagnose in adults and elderly since the virus titer in clinical samples is significantly lower and the virus is detectable for a shorter period in adults than in children.^1,38 Nasal, nasopharyngeal or oropharyngeal swab samples, saliva, sputum or bronchoalveolar lavage may be used for testing. Testing multiple samples has been reported to increase rates of establishing diagnosis.^2,42 When sputum is tested together with nasal/nasopharyngeal swab sample, the rate of diagnosis increases 1.4–2.0 times.^33,42 When 4 sample types are used (i.e. nasopharyngeal swab, saliva, sputum, and serology), the rate of diagnosis increases 2.60-fold compared to nasopharyngeal swab alone⁴²; however, obtaining multiple samples is not feasible in clinical practice. It has also been reported that, due to the lack of specific treatment for RSV, diagnostic tests are not performed for every patient, especially in outpatient settings. Additionally, multiplex PCR analysis cannot be widely implemented in LMICs due to its high cost. .¹⁷ In Türkiye, the multiplex-PCR test is reimbursed only for hospitalized patients.

Treatment

The main approach to the treatment of RSV infections is supportive (such as oxygen therapy, antipyretics, chest physiotherapy, and prevention of bedsore complications).³⁸ Although some antiviral drugs have been tested, there is no approved specific antiviral treatment for RSV in clinical practice.^2,43 Among adults hospitalized with RSV infection, 10% to 31% have been reported to require intensive care, with 3% to 17% requiring mechanical ventilation.¹⁸ This will pose a challenge in LMICs with limited resources and inadequate healthcare infrastructure. Türkiye is in a relatively good position in terms of the number of intensive care beds (39.6 per 100,000 population) compared to many HICs⁴⁴; however, during a high respiratory viral infection season, this capacity may still be overwhelmed due to high number of patients requiring hospitalization and intensive care. Thus, prevention of infection appears to be the most important strategy in combating RSV.

Preventive strategies for RSV infections

RSV is transmitted through contact with secretions of infected people and, less commonly, through droplets and contaminated surfaces.⁴⁵ Standard precautions such as hand washing, use of masks, eye protection, and isolation of the patient are recommended to prevent RSV infections.³⁰ Two monoclonal antibodies – palivizumab for infants in the risk group and nirsevimab for infant and young children – are currently approved for passive immunoprophylaxis to prevent RSV infection in children.^18,46 However, there are no adequate studies on the efficacy and cost-effectiveness of passive immunoprophylaxis in adults.¹⁸ Therefore, vaccination remains as a crucial tool to protect adults from RSV infection and its complications.

Vaccine studies have been ongoing for many years to provide active immunoprophylaxis in both children and adults. Five different approaches are used in vaccine development studies: live-attenuated, recombinant-vector, subunit, particle-based, and mRNA. Approximately 30 RSV vaccine candidates are currently in clinical trials worldwide, with more than 30 in preclinical evaluation.⁴⁷ There are 3 vaccines approved to date that are suitable for adult active immunization: RSVPreF3, RSVpreF, and mRNA-1345.⁴⁶ The general characteristics of these vaccines are summarized in Table 2.

Table 2.

Currently approved vaccines available for respiratory syncytial virus (RSV).

	RSVPreF3	RSVpreF	mRNA-1345
Trade name	Arexvy	Abrysvo®	mResvia™
Manufacturer	GlaxoSmithKline Biologicals SA	Pfizer Inc.	ModernaTX, Inc
FDA approval date	2023	2023	2024
Adjuvant	AS01E adjuvant	None	None
Mechanism	Subunit (protein) based	Subunit (protein) based	mRNA based
Indication	Individuals ≥60 years of age Individuals 50–59 years of age who are at increased risk for LRTI caused by RSV	Individuals ≥60 years of age Individuals 18–59 years who are at increased risk LRTI caused by RSV Pregnant women at 32–36 weeks gestational age	Individuals ≥60 years of age
Contraindication	History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.	History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine	History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine
Administration	a single dose; 0.5 mL; intramuscular	a single dose; 0.5 mL intramuscular	a single dose; 0.5 mL; intramuscular

Note: FDA, US Food and Drug Administration.

RSVPreF3 vaccine contains recombinant RSV glycoprotein F stabilized in the prefusion conformation (PreF) and the AS01E adjuvant system. RSVpreF is an adjuvant-free vaccine. RSVpreF is bivalent, containing an RSV prefusion F protein from both A and B. Although RSVPreF3 is not technically bivalent, it has been reported to demonstrate optimal efficacy against both A and B subtypes in clinical studies.¹⁸ mRNA-1345 is an unadjuvanted mRNA-based vaccine; it consists of lipid nanoparticles encapsulating the linear mRNA that encodes the RSV PreF protein.⁴⁸ mRNA vaccine also provides protection against subtypes A and B.⁴⁹

One of the approved RSV vaccines is administered as a single dose of 0.5 mL via intramuscular injection, given only once. The vaccine can be administered at any time.⁶

For protection against RSV in infants <6 months of age, maternal vaccination with one dose of RSVpreF is recommended between 32 and 36 weeks of pregnancy. Pregnant women beyond 36 weeks and 6 days should not be vaccinated, as there is insufficient time for antibodies to develop, cross the placenta, and provide protection to the baby. Timing of vaccination is difficult due to the annual changes in RSV circulation. Evaluation is ongoing to determine whether additional doses of RSV vaccine are beneficial in subsequent pregnancies for those who have received maternal RSV vaccine in a previous pregnancy; additional vaccination is not currently recommended.⁵⁰ Of RSV-associated deaths in children <5 years of age, 99% occur in LMICs. Due to this high burden of RSV, GAVI, the Vaccine Alliance, identified RSV interventions as one of its six priority areas for the 2021–2025 funding period.⁵¹ After vaccines become available, on 12 March 2025, the World Health Organization (WHO) prequalified the first maternal RSV vaccine. This prequalification aims to broaden access to RSV vaccines in LMICs, where the threat of severe illness and mortality is most significant.⁵²

Efficacy of RSV vaccines

The efficacy of RSV vaccines in adults aged ≥60 years is currently under evaluation through long-term clinical trials. AReSVi-006 study, an international, randomized, placebo-controlled, double-blind, ongoing study, has evaluated the efficacy of the RSVPreF3.⁵³ Over the course of one RSV season, the vaccine demonstrated an efficacy of 82.6% against overall RSV-related LRTI, 94.1% against severe RSV-related LRTI, and 71.7% against RSV-related acute respiratory infections (ARI) (Table 3).⁵³ The same study group also demonstrated a single dose of RSVPreF3 to be effective against RSV-LRTI over two RSV seasons.⁵⁴ According to a recent report on RSVPreF3 vaccine, the efficacy of a single dose against RSV-LRTI over three RSV seasons was 62.9% with season as a covariate and 69.1% without. Over three RSV seasons, the vaccine efficacy (VE) was 67.4% against severe RSV-LRTI and 51.1% against RSV-ARI (Table 3).⁵⁵ In a study in which the impact of the RSVPreF3 vaccine in adults aged 50–59 with an increased risk was estimated using a Markov model, based on the VE observed in the AReSVi-006 study, it was demonstrated that a single dose of the vaccine could significantly help reduce the burden of RSV disease over a 5-year period.⁵⁶

Table 3.

Effectiveness of approved respiratory syncytial virus (RSV) vaccines.

Vaccine	RSVPreF3			RSVpreF		mRNA-1345
Study	AReSVi-006			RENOIR		ConquerRSV
Population	Adults ≥60 years old			Adults ≥60 years old			Adults ≥60 years old
Study arms, N
Vaccine group	12467	12470*	12467	17215	16164		17793
Placebo group	12499	12503	12499	17069	16059		17748
Follow-up, months, median	6.7 (1 season)	17.8 (2 season)	30.6 (3 season)	6 (1 season)	17.6 (2 season)		3.7
RSV infections, n
LRTI-Overall	VG: 7, PG: 40	VG: 30, PG: 139		≥2 symptoms VG: 11, PG: 33 ≥3 symptoms VG: 2, PG: 14	≥2 symptoms VG: 39, PG: 88 ≥3 symptoms VG: 8, PG: 36		≥2 symptoms VG: 9, PG: 55 ≥3 symptoms VG: 3, PG: 17
LRTI-Severe	VG: 1, PG: 17	VG: 7, PG:48		-**	–		–
ARI	VG: 27, PG: 95	VG: 94, PG: 292		VG: 22, PG: 58	–		VG: 26, PG: 82
Vaccine Efficacy, %
LRTI-Overall	82.6	67.2	62.9	≥2 symptoms 66.7 ≥3 symptoms 85.7	≥2 symptoms 55.7 ≥3 symptoms 77.8		≥2 symptoms 83.7 ≥3 symptoms 82.4
LRTI-Severe	94.1	78.8	67.4	-**	–		–
ARI	71.7	62.7	51.1	62.1	36.9		68.4
References	53	54	55	57	58		49

*6,242 participants received a revaccination dose 1 year after the first dose. Revaccination was well tolerated but showed no added efficacy in the study group.

**Severe RSV-related LRTI was not analyzed due to insufficient cases at the cutoff date. ARI, acute respiratory infections; LRTI, lower respiratory tract infections; PG, Placebo group; RSV, Respiratory Syncytial Virus; VG, Vaccine group.

The RENOIR trial,⁵⁷ an international, randomized, placebo-controlled, double-blind study, has evaluated the VE of RSVpreF, where VE for RSV-related LRTI with at least 2 or at least 3 signs/symptoms (cough, wheezing, sputum production, shortness of breath, tachypnea) and for RSV-related ARI. The findings revealed that the VE of RSVpreF for RSV-related LRTI was 66.7% in patients with ≥ 2 symptoms, 85.7% in in patients with ≥ 3 symptoms, and %62.1 for RSV-related ARI.⁵⁷ The vaccine remained effective against RSV-related LRTI with ≥ 3 symptoms in the second season (VE, 77.8%) and the VE across two seasons was reported as 81.5%.⁵⁸ The recent final analysis of the RENOIR trial indicated that VE for RSV across two seasons was 76.3% for LRTI with ≥ 3 symptoms, 60.0% for LRTI with ≥ 2 symptoms, and 53.2% for ARI.⁵⁹ In a retrospective study conducted in the United States of America (USA), healthcare system records were reviewed and data from individuals aged ≥60 years with inpatient/emergency department LRTI events were analyzed.⁶⁰ The findings of the study revealed that RSVpreF vaccine was at least 90% effective in preventing RSV-related LRTI hospitalization/emergency department visits.⁶⁰ A study using a linear regression model based on the RENOIR trial results estimated decreasing VE over five possible RSV seasons and projected that VE would remain above 60% after five RSV seasons.⁶¹

In the international MATISSE study⁶² on maternal vaccination with RSVpreF vaccine, pregnant women between 24 and 36 weeks of gestation were administered with the vaccine (n = 3682) or placebo (n = 3676) in a 1:1 ratio. In interim analysis, VE in protecting infants against RSV-related severe LRTI was 81.8% at 90 days and 69.4% at 180 days; these rates were 57.1% and 51.3%, respectively, for LRTI.⁶² The final analysis of the MATISSE study also confirmed these findings. The VE for RSV-related LRTI was 82.4% and 70.0% within 90 and 180 days of birth, respectively.⁶³

The ConquerRSV study,⁴⁹ an international, randomized, placebo-controlled, double-blind, ongoing study, has evaluated the VE of mRNA-1345 vaccine. The VE was reported as 83.7% against RSV-related LRTI with ≥ 2 symptoms, 82.4% against RSV-related LRTI with ≥ 3 symptoms and 68.4% against RSV-related ARI (Table 3).⁴⁹ The study has also stated that further follow-up is ongoing to determine the duration of protection provided by the vaccine and to determine whether and when a booster dose is needed.⁴⁹

In their recent systematic review, Ricco et al.⁶⁴ reported that a pooled meta-analysis was not possible since the reported data of follow-up studies on the three approved RSV vaccines were from different seasonal periods; however, they conducted cumulative estimates across seasons separately for the vaccines. Accordingly, the VE of RSVPreF3, RSVpreF, and mRNA-1345 was estimated as 78.38%, 84.36%, and 62.88%, respectively, for protection against LRTI with ≥ 3 symptoms and as 67.73%, 52.42%, and 53.59%, respectively, for protection against ARI.⁶⁴

Safety of RSV vaccines

The RSV vaccines have generally been well tolerated in clinical studies. Most adverse events (AEs) are mild to moderate and regressed spontaneously. AEs of vaccines include local reactions such as pain, redness, and swelling at the injection site, and systemic reactions such as fatigue, headache, myalgia, joint pain, nausea, and tremors.^49,57,65

The interim analysis of the RSVPreF3 vaccine study (AReSVi-006) indicated in the solicited safety population that pain was the most frequently reported local reaction and fatigue was the most commonly reported systemic reaction (Table 4).⁵³ Up to the database lock for the safety analyses, the number of participants who experienced a serious AE (SAE) deemed by the investigator to be related to the vaccine or placebo was 10 (0.1%) in those who received the vaccine and 7 (0.1%) in those who received placebo, with nervous system disorders being the most frequently affected organ system class. There were 3 fatal SAEs – cardiopulmonary failure, pulmonary embolism, and an unknown cause of death, each occurring in 1 participant – deemed by the investigators to be related to trial intervention (vaccine or placebo, with group assignments remaining blinded). The alternative explanation stated by the authors of the AReSVi-006 study was that these deaths could possibly be related to preexisting risk factors (Table 4).⁵³ In the season 3 evaluation of the RSVPreF3 vaccine, it was reported that the frequency of SAEs remained low and similar in the vaccine and placebo groups throughout the study. No cases of Guillain-Barré syndrome or acute disseminated encephalomyelitis were reported until the end of the study.⁵⁵ However, in the recently presented findings of the AreSVi-004 study, 2 out of 1653 individuals (aged ≥60 years) who received at least one dose of the RSVPreF3 vaccine reported vaccine-related SAEs: one experienced Guillain-Barré syndrome on day 8 after the first dose, and the other experienced a seizure 5 hours after the second dose at month 12.⁶⁶

Table 4.

Safety of approved respiratory syncytial virus (RSV) vaccines.

Vaccine	RSVPreF3		RSVpreF		mRNA-1345
Study (Reference)	AReSVi-006 (53)		RENOIR (57)		ConquerRSV (49)
	Vaccine Group	Placebo Group	Vaccine Group	Placebo Group	Vaccine Group	Placebo Group
Solicited safety population, N	879	878	3,621	3,539	17,665	17,598
Solicited injection site reactions	n (%)	n (%)	%*	%*	n (%)	n (%)
Pain	535 (60.9)	81 (9.3)	11	6	9942 (56.3)	2407 (13.7)
Erythema	66 (7.5)	7 (0.8)	3	1	357 (2.0)	101 (0.6)
Swelling	48 (5.5)	5 (0.6)	2	<1	662 (3.7)	59 (0.3)
Solicited systemic reactions	n (%)	n (%)	%*	%*	n (%)	n (%)
Fatigue	295 (33.6)	141 (16.1)	16	14	5470 (31.0)	3518 (20.0)
Myalgia	254 (28.9)	72 (8.2)	10	8	4574 (25.9)	2542 (14.4)
Headache	239 (27.2)	111 (12.6)	13	12	4764 (27.0)	3332 (18.9)
Arthralgia	159 (18.1)	56 (6.4)	–	–	3867 (21.9)	2477 (14.1)
Fever	18 (2.0)	3 (0.3)	1	1	501 (2.8)	234 (1.3)
Exposed population, N	12,467	12,499	17,215	17,069	17,734	17,679
Adverse Events	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Any AE	4117 (33.0)	2229 (17.8)	1544 (9.0)	1453 (8.5)	3624 (20.4)	3331 (18.8)
AE related to trial intervention	3105 (24.9)	731 (5.8)	239 (1.4)	163 (1.0)	1033 (5.8)	803 (4.5)
SAE related to trial intervention	10 (0.1)	7 (0.1)	-**	-**	4 (<0.1)	3 (<0.1)
Fatal SAE related to trial intervention	3 (-)***	3 (-)***	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

Note: AE, adverse event; SAE; severe adverse event. *In the relevant cited article, only percentage values were provided. ** Three participants reported a SAE considered by the investigator to be related to trial intervention; however, it was not specified which group the SAE belonged to. ***Three fatal SAEs were considered to be related to vaccine or placebo administration. Explanation is given in the text.

The interim analysis of the RSVpreF vaccine study (the RENOIR trial) reported that the incidence of local reactions was higher with the vaccine (12%) than with placebo (7%); the incidences of systemic events were similar (27% and 26%) (Table 4).⁵⁷ Severe or life-threatening AEs were reported in 0.5% of those who received the vaccine and 0.4% of those who received placebo. At the data cutoff date, there were three SAEs deemed by the investigators to be related to the trial intervention. The first SAE was a delayed allergic reaction that resolved on the same day. The second SAE which was a retrospective diagnosis consistent with Miller-Fisher syndrome (a subset of Guillain-Barré syndrome) in a diabetic patient who recovered without undergoing a spinal tap or nerve conduction studies. The third SAE was a myocardial infarction which was subsequently also diagnosed with acute inflammatory demyelinating polyradiculoneuropathy, consistent with Guillain-Barré syndrome; the patient regained most of his motor function. No deaths associated with vaccines have been recorded in that study.⁵⁷ In the recent final analysis of the study, a consistent favorable safety profile was reported.⁵⁹

In the maternal vaccination study (MATISSE), the incidences of maternal and infant AEs and SAEs were similar with the vaccine and placebo. Four recipients of the RSVpreF vaccine experienced one SAE each (pain in one arm and lower limbs/preterm birth/systemic lupus erythematosus/eclampsia), while a placebo recipient experienced one SAE (premature placental separation), all of which were assessed by the investigator as being injection related. No SAE in infants was evaluated as vaccine-related.⁶² In the final analysis of the study, it was confirmed that the vaccine has an appropriate safety profile for pregnant women and newborns, and no additional safety concerns were identified.⁶³

In the mRNA-1345 vaccine study (the ConquerRSV study), participants who received the vaccine had a higher incidence for local AEs (58.7% vs. 16.2%) and systemic AEs (47.7% vs. 32.9%) as compared with those who received placebo; most reactions were mild to moderate in severity and were transient.⁴⁹ Until the data-cutoff date, SAEs occurred in 2.8% of the participants in each group. SAEs that were assessed by the investigator as injection-related were reported in < 0.1% of participants in each group. Until the data-cutoff date, no cases of acute disseminated encephalomyelitis or Guillain-Barré syndrome were observed in the groups. No deaths associated with vaccines have been recorded (Table 4).⁴⁹

Cost-effectiveness of RSV vaccines

RSV has a significant economic burden, of which hospitalization costs constitute most of the total economic burden. In the US, the annual national direct cost burden of RSV-associated hospitalizations is estimated to be $1.3 billion for all adults.⁶⁷

In cost-effectiveness studies, RSV vaccination has been shown to provide direct health benefits and prevent productivity losses by significantly reducing the disease burden in adults.^68–71 Nevertheless, it has been suggested that population-level data are necessary to demonstrate the long-term health benefits and cost-effectiveness of vaccination beyond the season.⁶⁹ Molnar et al.⁷² evaluated the impact of RSVPreF3 vaccine on public health among adults aged ≥60 years in the USA in their study using a multi-cohort Markov model. Based on the results of the analysis, it was estimated that if approximately 56.7 million adults aged ≥60 years were vaccinated, there would be 2,954,465 fewer cases of symptomatic RSV-associated acute respiratory illness, 321,019 fewer cases of pneumonia, and 16,660 fewer RSV-associated deaths compared to no vaccination over 3 years. Vaccination was also predicted to prevent a significant number of RSV-related hospitalizations (203,891), emergency room visits (164,060), outpatient visits (1,577,586), and antibiotic prescriptions (1,343,915) over the 3-year period. These findings highlight the potential for RSVPreF3 vaccine to significantly reduce the RSV disease burden in older adults aged ≥60 years.⁷²

A recent report evaluated the socioeconomical value of adult immunization programs against four infections (influenza, pneumococcal, herpes zoster, and RSV) in 10 countries (Australia, Brazil, France, Germany, Italy, Japan, Poland, South Africa, Thailand, and USA).⁷³ The report found that adult immunization programs offset their costs several times over through benefits to individuals, the health system, and society, resulting in net monetary benefits to society of billions of dollars. The report also stated that cost-benefit analyses showed that these adult vaccines could provide a return of up to 19 times the initial investment to society.⁷³

RSV vaccination recommendations

The immunization strategy for RSV, including who should be vaccinated and whether it should be seasonal or administered at any time, is country-specific and depends on costs, sociocultural characteristics, and healthcare infrastructure.⁷⁴ The RSV vaccines have been recommended by advisory committees or health authorities in many countries around the world, and the vaccine is included or planned in the adult vaccination program.^75–90 The US CDC/Advisory Committee on Immunization Practices (ACIP) has recommended that all adults aged ≥75 years and adults aged 60–74 years who are at increased risk for severe RSV disease should receive a single dose of RSV vaccine.⁶ As of April 16, 2025– during the preparation of this manuscript – the ACIP voted to expand its recommendation for RSV vaccine RSVpreF to include adults aged 50 to 59 at increased risk of disease. The updated ACIP recommendation is pending final approval by the director of the CDC and the Department of Health and Human Services.⁹¹

Examples of RSV vaccination recommendations by advisory committees or health authorities in various countries are summarized in Table 5. As evident in the Table, RSV vaccination is recommended in HICs. RSV vaccines are not available in most LMICs. Given that RSV infections pose a greater burden in LMICs, it is important that vaccines are equitably distributed to include these countries and that access is provided to at risk populations. It has been emphasized that urgent steps should be taken to close the RSV vaccination gap between HICs and LMICs.^74,92

Table 5.

Respiratory syncytial virus (RSV) vaccination recommendations by advisory committees or health authorities in various countries.

Country	General (age, years)	At risk/Special condition (age, years/property)	Maternal (only RSVpreF)	Reference
USA	≥75	60–74/at increased risk for severe RSV disease	24–36 weeks of gestation	75
Canada	≥75	≥60/residents of nursing homes and chronic care facilities 60–74/Individual decision with health provider consultation		76
UK	≥75			77
Ireland	≥65			78
Germany	≥75			79
France	≥75	≥65/with chronic respiratory or heart pathologies		80
Belgium		>60/with at least one risk factor of severe RSV disease		81
Austria	≥60	≥18/with underlying medical conditions	24–36 weeks of gestation	82
Norway		≥60/with underlying medical conditions	24–36 weeks of gestation	83
Sweden	≥75	≥60/with certain underlying diseases	24–36 weeks of gestation	84
Switzerland	≥75	≥60/with increased risk of complications 18–59/Individual decision with health provider consultation	32–36 weeks of gestation	85
Poland	≥60			86
Italy	≥75	≥60/with increased risk of complications		87
Greece	≥75	≥60/with concomitant medical conditions		88
Australia	≥75	≥60/Aboriginal and Torres Strait Islander people ≥60/with medical risk factors for severe RSV disease	28–36 weeks of gestation	89
Saudi Arabia	≥60			90

Various professional medical societies and authorities have also made recommendations regarding target populations for RSV vaccines in many countries, including those where RSV vaccine is not included in the NIP.⁹³ The US CDC/ACIP recommendations for RSV vaccination were highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 report⁹⁴ and the American Diabetes Association (ADA) Standards of Care in Diabetes 2024 report.⁹⁵ The American College of Obstetricians and Gynecologists (ACOG) also recommends maternal RSV vaccination for pregnant women who are between 32–36 weeks of gestation and are not planning to give birth within 2 weeks.⁹⁶ In a collaborative position paper by leading German medical societies and organizations, it was stated that adults of all ages with serious pulmonary or cardiovascular disease or significant immune deficiency could receive RSV vaccination after individual consultation with their physician.⁹⁷ In Spain, the NeumoExperts Prevention Group Position Paper suggested that RSV vaccines should be part of the adult immunization program and that an age-based (≥60 years) strategy should be preferred rather than targeting high-risk groups.⁹⁸ In Portugal, a position paper on the implementation of RSV vaccination was published with the participation of many professional associations. It was recommended that RSV vaccination should be administered to all adults aged ≥60 years and to those aged ≥50 years with risk factors. If this is not possible, it was stated that priority should be given to adults aged ≥75 years and to those aged ≥50 years with risk factors.⁹⁹ RSV vaccines have been recommended by the Mexican Interdisciplinary Consensus for older adults (aged ≥75 years and aged ≥60 years with risk factors) and pregnant women (between 32 and 36 weeks of gestation).¹⁰⁰ Taiwan Immunization Vision and Strategy recommends RSV vaccination for adults aged ≥75 years, adults aged 60–74 years with risk factors, adults aged 60–74 years without risk factors after shared decision-making, and pregnant women between 28 and 36 weeks of gestation.¹⁰¹ Boattini et al.¹⁰² recommended RSV vaccination especially for elderly people who have diabetes, chronic organ diseases, immune deficiency, live in long-term care facilities, or are frequently in contact with young children. Osei-Yeboah et al.¹⁰³ indicated that older adults in nursing and care homes (NCHs) are more vulnerable to severe RSV infection, hospitalization, and death; thus, RSV vaccination should be planned as a priority for this high-risk population. Although vaccination against RSV is widely reimbursed or recommended in the adult vaccination programs almost in all HICs, this is not the case for the rest of the world. There is a large room for improvement from the equity lens as everyone deserves to be protected regardless of the socioeconomical status of the individual or the income level of the country. Considering the age groups for which vaccination is recommended, in Türkiye, there are 3.1 million people over 75 years of age and 9.6 million people between 60–74 years of age.¹⁰⁴ Around 30% of all adults have at least one chronic disease or risk factor (such as obesity, smoking etc.),^105,106 this rate reaches approximately 70% among individuals aged ≥65 years for whom RSV vaccination is indicated as per the scientific evidence and recommendations. In Türkiye, childhood and selected risk group vaccination programs (including pregnancy vaccination) are mainly carried out for free through primary health services (family health centers). Moreover, since individuals have direct access to secondary and tertiary healthcare services, vaccination outpatient clinics and units in these centers are also involved in vaccination practices. Currently, RSVpreF and RSVPreF3 vaccines have been licensed in Türkiye but are not yet included in the reimbursement scope. They can be bought and administered by obtaining a physician’s prescription. Awareness is rising with more and more national scientific associations recommending the RSV vaccine.^107–111

We therefore suggest that, for Türkiye,

• As epidemiological data and surveillance studies highlight the significance of RSV infections, surveillance systems should be maintained and the epidemiological data should be used to tailor the immunization policies.

• In order to protect infants (by vaccinating pregnant women), the elderly, and adults in high-risk groups from RSV infection and its possible complications, the inclusion of RSV vaccine in the national immunization program should be considered.

• While maintaining a strong primary care engagement for adult vaccination, the number of adult vaccination outpatient clinics and units should also be increased to facilitate easier access to vaccinations. These clinics should maintain an adequate supply of vaccines.

• Systematic evidence-based adult education approaches through scientific meetings, in-service training, and online learning platforms should be implemented in order to enhance awareness and increase trust in the vaccines among both the general population and healthcare professionals – including physicians, nurses, midwives, and pharmacists.

Conclusion

RSV is a serious health problem in adults, especially in the elderly, as is in children. As a result of the widespread use of diagnostic methods, the burden of RSV infections in older adults has become better understood with the accumulation of epidemiological data. The RSV burden is comparable to that of influenza. Three RSV vaccines have recently been approved for use in older adults and the effectiveness and safety of vaccines have been shown in studies. Physicians should be aware that RSV infections are not just a simple childhood illness but can lead to serious outcomes, especially in older adults and those with comorbidities. It is important for physicians to recognize the true extent of health and economic burden of RSV and the benefits of vaccination. By increasing awareness among physicians, together with more common use of diagnostic tests and a purposeful surveillance system, RSV epidemiology in adults (especially in risk groups and the elderly) will be better understood and will guide in determining the vaccination strategy. Preventing RSV infections in adults will provide individual and social gains; therefore, in line with the up-to-date scientific data and practice recommendations throughout the world, RSV vaccine should be included in the adult vaccination program together with an effective lifelong immunization strategy.

Biography

Mine Durusu Tanriover graduated from Hacettepe University Faculty of Medicine in 2000 and finished her residency training in internal medicine in 2005 in the same university. She served as the consultant of the Acute Care Unit and Emergency Department for several years, mainly admitting patients with acute decompensation of chronic diseases; lower respiratory tract infections, organ failure and acute, undiagnosed conditions.

Prof. Dr. Mine Durusu Tanriover worked as the Co-Chief of Hacettepe University Oncology Hospital and the Quality Coordinator of Hacettepe University Hospitals, a Joint Commission International accredited academic medical center between 2016-2020. Her research area mainly consists of adult vaccination, vaccine preventable diseases, influenza, quality improvement and patient safety. She has been involved in the Global Influenza Hospital Surveillance Network project as an investigator and site coordinator since 2012 and participated as an investigator in the phase 3 clinical trials of COVID-19 vaccines available in Türkiye.

She is the founder and the first chair of the Young Internists Working Group, honorary fellow of the European Federation of Internal Medicine (EFIM) and the Editor-in-Chief of EFIM Academy. Dr. Durusu Tanriover is currently the Secretary of the Middle East, Eurasia and Africa Influenza Stakeholders Network (ME’NA-ISN).

Funding Statement

This study was sponsored by Pfizer. Medical writing support was provided by Omega CRO, Ankara, Türkiye and was funded by Pfizer.

Disclosure statement

Mine Durusu Tanriover has received honoraria from Sanofi Pasteur, Pfizer, Abbott, GSK, MSD for consultancy and scientific presentations and has no conflict of interest directly related to this work. Alpay Azap has received honoraria from Pfizer, GSK, Astellas, MSD for scientific presentation and has no conflict of interest directly related to this work. Hasan Selcuk Ozger has received honoraria from Pfizer for consultancy and lectures. Abdullah Sayiner has received honoraria from Pfizer, GlaxoSmithKline, Abbott and Sanofi for consultancy and lectures. Oldac Uras Dursun and Seyhmus Merter are the employees of Pfizer Inc. Ebru Cakir Edis, Husnu Pullukcu, and Meliha Cagla Sonmezer report there are no competing interests to declare.

Author contributions

Mine Durusu Tanriover contributed to the conception and design and analysis and interpretation of the data. All authors drafted the paper, revised it critically for intellectual content, and provided final approval of the version to be published. All authors agree to be accountable for all aspects of the work.