Rhinovirus/enterovirus contribution to respiratory-associated hospitalizations in adults during respiratory seasons in Spain: A 6-year prospective study

Sandra S. Chaves; Valérie Bosch Castells; Ainara Mira-Iglesias; Joan Puig-Barberà; F. Xavier López-Labrador; Miguel Tortajada-Girbés; Mario Carballido-Fernández; Joan Mollar-Maseres; Germán Schwarz-Chávarri; Javier Díez-Domingo; Alejandro Orrico-Sánchez; Valencia Hospital Network for the Study of Influenza and other Respiratory Viruses (VAHNSI)

doi:10.1371/journal.pone.0347659

Abstract

Background

Understanding the burden of acute viral respiratory infection-related hospitalizations is crucial for guiding research and development. Unlike influenza, respiratory syncytial virus (RSV), or severe acute respiratory syndrome coronavirus 2, no pharmaceutical interventions exist for other respiratory viruses; therefore, their impact remains poorly characterized. This study aimed to investigate the association of current non-vaccine-preventable respiratory viruses, especially rhinovirus/enterovirus (RV/EV), on hospitalizations during the respiratory seasons.

Methods

Data from a prospective study that used multiplex polymerase chain reaction to conduct long-term surveillance on respiratory viruses in Valencia, Spain were analyzed. Patients aged ≥50 years hospitalized due to respiratory illness from 2014–15–2019–20 were included.

Results

Respiratory viruses were detected in 35.2% (3,755/10,675) of hospitalized patients with acute respiratory illness. Influenza and RSV accounted for 22.1% of hospitalizations, RV/EV for 7.6%, and other non-vaccine-preventable viruses for 5.4%. Adults ≥75 years had average seasonal hospitalization incidence rates more than twice those aged 65–74 years and eight times those aged 50–64-year-olds. No significant differences in severity markers were observed among patients with or without virus identified, those aged ≥75 years had a 2–3 times higher mortality rate compared to younger age groups.

Conclusions

The potential impact of respiratory viruses on hospitalization rates among older adults, particularly those aged ≥75 years, highlights the need for targeted interventions to reduce healthcare system burden. Enhanced diagnostic capabilities and the development of next-generation preventive strategies, including vaccines and therapeutics, could improve patient outcomes and strengthen the resilience of the healthcare system during respiratory virus seasons.

Citation: Chaves SS, Castells VB, Mira-Iglesias A, Puig-Barberà J, López-Labrador FX, Tortajada-Girbés M, et al. (2026) Rhinovirus/enterovirus contribution to respiratory-associated hospitalizations in adults during respiratory seasons in Spain: A 6-year prospective study. PLoS One 21(4): e0347659. https://doi.org/10.1371/journal.pone.0347659

Editor: Flora De Conto, Università degli Studi di Parma: Universita degli Studi di Parma, ITALY

Received: November 13, 2025; Accepted: April 6, 2026; Published: April 20, 2026

Copyright: © 2026 Chaves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The data that supports the findings of this study are available from the authors upon reasonable request, and with the permission of FISABIO-Public Health study committee. The data are not publicly available due to privacy restrictions to potentially identifying data as identified within the Research Ethics Committee application/approval. Please contact Fisabio Foundation (vacunas@fisabio.es) for data requests.

Funding: This study received partial funding from Sanofi, the Fondation de France, FISABIO-Public Health, and CIBER-ESP. Unlike the other funders, the Fondation de France and CIBER-ESP had no involvement in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. Some of the authors have affiliations with Sanofi and FISABIO-Public Health. Sanofi did not participate in the data collection, but SSC and VBC were involved in the analysis, interpretation and writing of this manuscript as stated in the Authors’ contribution section.

Competing interests: The following updated statement has been included in the cover letter “SSC and VBC are employees of Sanofi and may hold shares and/or stock options in the company. JD-D and AO-S have attended several congresses, whose registration, travel, and accommodation costs were covered by MSD, GSK, AZ, and Sanofi Pasteur (SP). AM-I has attended congresses, whose registration, travel, and accommodation costs were covered by MSD and SP. AO-S and JD-D, along with their institution, have received research grants from SP and GSK. AO-S and JD-D have acted as advisers for SP, with AO-S also advising Moderna. AM-I has received fees for conferences/experts’ meetings from SP and for educational events from MSD. FXL-L received grants from the Foundation for Influenza Epidemiology (France), payments to his institution from SP and CIBER-ESP (Instituto de Salud Carlos III, Spain), and individual payments for advisory boards from SP. FXL-L also holds a leadership role in the European Society of Clinical Virology as an Executive Member. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction

Lower respiratory tract infections are a leading cause of morbidity and mortality globally, affecting the very young and the elderly disproportionately [1]. In Europe, respiratory system diseases are the third most common cause of death [2], contributing significantly to the public health burden. Among respiratory pathogens, influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) are major contributors to severe illness and mortality among adults with underlying chronic medical conditions and those 65 years and older [1,3–5]. There are relatively robust surveillance systems to monitor these viruses; however, other respiratory viruses, such as parainfluenza virus, human metapneumovirus (HMPV), and human rhinovirus (RV), remain comparatively understudied in these populations, despite mounting evidence of their role in infections leading to hospitalizations [6–9].

In temperate regions, especially during winter months, all these viruses co-circulate, adding pressure to respiratory illness associated healthcare utilization [10,11].Vaccines and therapies for influenza [12], RSV [5], and SARS-CoV-2 [13] are currently available. However, there are no pharmaceutical interventions for other respiratory viruses. Hence, their clinical and epidemiological impact remains inadequately characterized, creating a significant knowledge gap in respiratory disease management.

To improve our understanding of the contribution of other respiratory viruses to hospitalizations among adults, we analyzed data from a prospective study examining patients aged ≥50 years hospitalized because of respiratory illness. We used comprehensive viral panel testing to investigate the relative impact of different respiratory viruses on hospitalization incidence rates and disease severity during the respiratory season, while focusing on characterizing the impact of RV infections separately. However, because of the genetic similarities between enterovirus (EV) and RV, the molecular methods we used may have misclassified some EV as RV, as available assays based on the highly conserved 5′ non-coding region may not distinguish between these viruses for an accurate diagnosis [14]. Therefore, we reported laboratory results as combined RV/EV positive results for our analysis, where the associated hospitalizations occurred in the respiratory season, where RV circulation peaks in the fall months [15,16].

Materials and methods

Study setting and design

We analyzed hospital‐based active-surveillance data obtained from the Valencia Hospital Surveillance Network for the Study of Influenza and Other Respiratory Viruses (VAHNSI) in Valencia, Spain. VAHNSI conducted prospective active surveillance on patients hospitalized because of acute respiratory illness from November 1 through March 31 (respiratory season). Although the surveillance was conducted on patients of all ages, our analysis focused on patients aged ≥50 years who were hospitalized during the respiratory seasons, from 2014–15–2019–20. The 2019–20 season was interrupted on March 14^th, when the government approved the declaration of a state of emergency throughout Spain to deal with the health emergency caused by SARS-CoV-2. Ten hospitals provided data in the 2014–15 season and four hospitals during the other seasons. The catchment area of these hospitals covered 21% to 46% of inhabitants in Valencia Region (approximately 5 million) of Spain. The study methodology has been previously described [17].

Case definition and enrollment

Residents in the catchment area of one of the participating hospitals who were non-institutionalized and had not been discharged from a previous admission in the past 30 days were eligible to be enrolled if they were hospitalized because of acute respiratory illness, which was defined as at least one respiratory (cough, sore throat, or shortness of breath) and one systemic (fever or feverishness, headache, myalgia, or malaise) sign/symptom with an onset of ≤7 days [18]. Detailed clinical and demographic data were gathered through patient interviews and medical chart abstraction after obtaining informed consent from patients.

Data collection

The demographic data collected for this study included sex, age at the day of admission, smoking status, body mass index (BMI), and functional dependency (measured by the Barthel index for patients aged ≥65 years). Clinical data collected included the length of hospital stay (LOS), the presence of chronic medical conditions, admission to the intensive care unit (ICU), the use of mechanical ventilation, and the date of discharge or death. Chronic medical conditions included heart disease, cerebrovascular disease, peripheral arteriopathy, asthma, lung disease, diabetes, endocrine system disease other than diabetes, anemia, chronic liver disease, chronic renal disease, chronic autoimmune disease, neurological/neuromuscular diseases, and neoplastic disease.

Laboratory methods

Nasopharyngeal and/or oropharyngeal swabs were obtained from each patient. Swabs were placed in a single 3-mL Universal Transport Medium tube (Copan, Italy) and stored at ≤−20 °C at the study site or dispatched refrigerated directly to the reference laboratory of the coordinating site for testing. Samples were collected within 48 h of hospital admission and tested in batches of 22 at a centralized laboratory (FISABIO-Public Health, Valencia, Spain). One-third of the viral transport medium volume (1 mL) was used for the extraction of total nucleic acids using an automated silica-based method (Nuclisens Easy-Mag, BioMérieux, Lyon, France). Subsequently, the extracted nucleic acids were analyzed using a real-time reverse transcription polymerase chain reaction (RT-PCR) multiplex panel to test for the presence of adenovirus, bocavirus, seasonal human coronaviruses (229E, HKU1, NL63, and OC43), HMPV, parainfluenza viruses [1–4], RSV (A/B), RV (A/B/C), and influenza (A/B), as described previously [17], using Roche LightCycler^® 480 II with some modifications. An additional RV primer was included for enhanced detection of RV-C species [19], the master mix used from 2015 onward was qScript XLT 1-Step RT-qPCR ToughMix (Quantabio, MA, USA), and probes for RSV-B were updated in 2017 [20]. Because the genetic similarities between EV and RV, the results are presented as EV/RV to account for cross-reaction among these viruses.

Statistical analyses

For this analysis, we categorized patients into age groups 50–64 years, 65–74 years, and ≥75 years. The LOS was recorded as the number of nights spent in the hospital. Admission to the ICU, need for mechanical ventilation, LOS, and deaths were considered markers of disease severity, and severe cases were defined as patients who were admitted to the ICU, required mechanical ventilation, or died during hospitalization (as a composite variable). We also grouped the viral results into the following categories: vaccine-preventable (i.e., influenza viruses and RSV), RV/EV, and other non-vaccine-preventable viruses (i.e., HMPV, parainfluenza viruses, adenovirus, seasonal human coronaviruses, and bocaviruses). We excluded all cases with viral co-detections to report only the impact of individual virus on hospitalizations.

Categorical data were described as proportions and compared using Chi-square tests, or Fisher’s exact tests as appropriate. Continuous data were compared using Student’s t-tests, or Wilcoxon tests when the conditions for applying a student’s t-test were not met. A p-value <0.05 indicated statistical significance. Incidence rates were calculated as the number of hospitalizations divided by the population of the VAHNSI catchment area stratified by age group and expressed per 100,000 individuals during each defined season. We estimated the mean incidence rates by hospitalization category and patient age, and then, presented the mean incidence (observed across the seasons) and the maximum and minimum rates for specific seasons. All analyses were conducted using R software.

Ethics declaration

The Ethics Research Committee of the Dirección General de Salud Pública-Centro Superior de Investigación en Salud Pública (DGSP-CSISP) approved the original protocol of the study. Patients included in this analysis were enrolled from November 10^th 2014 through March 14^th 2020, providing written informed consent before their inclusion. Additional information regarding the ethical, cultural, and scientific considerations specific to inclusivity in global research is included in the Supporting Information.

Results

Demographic characteristics and underlying medical conditions

From 2014–15–2019–20, 10,833 patients aged ≥50 years were hospitalized because of acute respiratory illnesses. A total of 64 samples that were damaged, lost, or yielded inconclusive results and an additional 94 cases with viral co-detections were excluded. We included 10,675 patients in this analysis. Of these patients, 60.4% were ≥75 years old, 53.4% were male, 47% had never smoked, 31.8% had a normal BMI, and 56.7% had minimal functional dependency. The majority (89.6%) of hospitalized patients had at least one underlying chronic disease, the most common being heart disease (50.9%), followed by lung disease (36.0%) and diabetes (33.3%). Almost one-third of hospitalizations (29.5%) were registered during the 2014–15 season (wherein 10 hospitals participated in the surveillance), whereas <10% occurred during the 2019–20 season, which was impacted by the emergence of SARS-CoV-2 (Table 1).

Download:

Table 1. Demographic characteristics of patients aged ≥50 years hospitalized because of acute respiratory illness, by the presence of single respiratory viruses detected or no virus detected. Valencia, Spain, 2014–2020.

https://doi.org/10.1371/journal.pone.0347659.t001

The characteristics of hospitalized patients identified at admission were similar among those with or without respiratory virus detection. The percentage of hospitalizations associated with the 2017–18 season in the group with respiratory viruses (20.9%) was higher than that in those without detectable respiratory viruses (13.1%) (Table 1). Patients’ demographic characteristics were similar when compared by season (S1 Table).

Time-dependent variation on virus detection

A virus was detected in specimens from 3,755 (35.2%) patients, with seasonal variation in their contribution to acute respiratory hospitalizations—ranging from 23.5% in 2019–20 to 46.4% in 2017–18 (Fig 1A). The monthly contribution of different viruses showed significant patterns: vaccine-preventable viruses (influenza and RSV) accounted for 10% to 85% of viral hospitalizations, depending on the month and season. RV/EV-associated hospitalizations dominated the early respiratory season (November to December), whereas vaccine-preventable virus hospitalizations typically peaked between January and February, except for the 2015–16 season that showed a delayed peak in March (Fig 1B).

Download:

Fig 1. Contribution of respiratory viruses to overall acute respiratory-associated hospitalizations during the respiratory seasons among adults aged ≥50 years in Valencia, Spain, 2014-2020.

(A) shows the total number of hospitalizations by season and the contribution of single virus detection, indicated in percentage. (B) shows the monthly distribution of vaccine-preventable viruses (influenza and RSV), rhinovirus/enterovirus and other non-vaccine-preventable viruses (parainfluenza viruses, adenovirus, seasonal coronavirus, HMPV, and bocavirus) to the volume of hospitalizations among those with single virus detected by season.

https://doi.org/10.1371/journal.pone.0347659.g001

Severity of hospitalization by virus type

The median LOS among all hospitalized patients with respiratory illness was 6 days (interquartile range: 4–8 days), with 2.0% of them admitted to the ICU and 5.3% requiring mechanical ventilation, and 5.1% died while hospitalized. Hospitalizations were characterized as severe for 10.8% of patients. Univariate analysis showed that severity markers did not differ whether respiratory viruses were detected or not or whether the hospitalization was associated with vaccine-preventable viruses (Table 2).

Download:

Table 2. Severity indicators of hospitalizations with and without respiratory virus detected at admission and whether the virus detected were vaccine preventable or not, with distribution by age group. Valencia, Spain 2014–2020.

https://doi.org/10.1371/journal.pone.0347659.t002

The analysis by age group showed that mortality rate was two to three times higher among those aged ≥75 years than that among their younger counterparts, and the difference was significant whether the virus detected was vaccine-reventable or not. There were significantly more ICU admissions among patients aged 50–64 years in the group of vaccine-preventable viruses. The number of patients admitted to the ICU was small for the other categories.

Incidence rate

Among adult population aged ≥50 years, the seasonal mean rate of acute respiratory illness hospitalizations was 357.5 per 100,000 population, ranging from 234.4 to 410.4 per 100,000 population during the study period. Of these, hospitalizations with a single virus detected at admission averaged 125.8 per 100,000 population (S2 Table; Fig 2A). Vaccine-preventable viruses were responsible for 63% of the cases (78.8 per 100,000 population), whereas RV/EV accounted for 22% (27.8 per 100,000 individuals) (Fig 2B). Those aged ≥75 years were disproportionally represented, with the overall average seasonal hospitalization rate of 925.9 per 100,000 individuals compared with that of 328.9 per 100,000 individuals among those aged 65–74 years and 118.1 per 100,000 individuals among those aged 50–64 years (S2 Table; Fig 2A). A similar distribution of hospitalization rates by age group was observed regardless of whether the detected virus was vaccine-preventable or not, meaning that the hospitalization rates for those aged ≥75 years were nearly three times higher than those aged 65–74 years and seven to nine times higher than those aged 50–64 years.

Download:

Fig 2. Acute respiratory-associated hospitalizations by age group and potential viral etiology (A) shows mean annual incidence of hospitalizations per 100,000 individuals associated with acute respiratory hospitalizations during the respiratory seasons, with and without virus detected at admission, and, among those with single virus detected, the distribution of vaccine-preventable and non- vaccine-preventable respiratory viruses, by age group in Valencia, Spain, 2014–2020.

(B) shows the percentage distribution of the respiratory viruses (vaccine preventable, rhinovirus/enterovirus, and other non-vaccine preventable) to overall mean hospitalization incidence rates for viral associated hospitalizations.

https://doi.org/10.1371/journal.pone.0347659.g002

Discussion

Our findings demonstrate that respiratory viruses were detected in approximately one-third of all acute respiratory-associated hospitalizations in adults aged ≥50 years during the respiratory season (November through March) from 2014 to 2020, varying from ~20% to 46% depending on the season. Although influenza and RSV—both vaccine-preventable—accounted for most virus-associated hospitalizations, other respiratory viruses have also potentially impacted overall hospitalization rates. Notably, RV/EV were detected in 22% of viral respiratory hospitalizations, surpassing the combined contribution of all other non-vaccine-preventable viruses. Adults aged ≥75 years were disproportionally affected, with the mean seasonal hospitalization incidence rates more than twice as high than those aged 65–74 years and approximately eight times higher than adults aged 50–64 years. Mortality rates in the oldest age group (≥75 years) were also significantly elevated compared with the younger cohorts. Severity markers showed no significant differences between virus-positive and virus-negative cases or between vaccine-preventable and non-vaccine-preventable viral infections. These findings highlight the substantial respiratory health burden among adults aged ≥75 years and suggest that interventions targeting viral respiratory infections in older adults could greatly reduce the burden on the healthcare system, particularly in hospital settings.

In our study, we identified viruses in 35.2% of patients aged ≥50 years hospitalized because of respiratory illness. It is difficult to compare the rate of detection across studies because of the variations in methodology and case definitions. Our approach employed a broad yet standardized case definition for acute respiratory hospitalizations. Comparable positivity rates were reported in a US study using physician-driven testing (as part of the standard of care) [21] and in other European studies using different screening approaches [22,23]. A French study, which employed a similar case definition, found a virus detection rate (>50%) that was higher than that of our study (35.2%) [10], probably because the French study included a broad age range of adults (i.e., 18 years and older).

Importantly, consistent with previous studies, we demonstrated frequent co-circulation of several respiratory viruses during the respiratory season in Valencia, Spain, as reported in other Northern Hemisphere countries [10,11,24,25]. Nonetheless, RV/EV circulation extends beyond the conventional respiratory season, with year-round presence documented in numerous studies [8]. A study examining the distribution of viral respiratory hospitalizations in and out of the respiratory season showed that RV/EV was associated with as many hospitalizations during spring/summer as during winter [26]. This suggests that RV/EV likely impacts healthcare resource utilization throughout the year, which in turn implies a possible underestimation of hospitalization incidence rates when only the respiratory season period is considered.

Among more severe clinical presentations, RV has been associated with exacerbations of chronic respiratory illnesses, such as asthma, chronic obstructive pulmonary disease, and chronic bronchiolitis [6,7,9]. Our analysis revealed comparable rates of ICU admission, mechanical ventilation use, mortality, and LOS between patients with and without detected respiratory viruses. Furthermore, we observed no significant differences in these outcomes between patients with vaccine-preventable and non-vaccine-preventable viral infections. These findings suggest that upon hospitalization, the severity of outcomes associated with RV/EV and other non-vaccine-preventable viral infections may be comparable to those associated with vaccine-preventable viruses such as influenza and RSV, particularly among those aged ≥75 years, as the number of younger patients in these categories was less robust. The severity associated with RV/EV and other respiratory virus infections has been reported in other studies [24,27], although in-hospital severity outcomes may reflect admission thresholds and host factors rather than intrinsic viral virulence. Further investigations using more robust data and adjustments for confounders are warranted. Despite variability in study designs, many respiratory viruses have been shown to cause severe disease (including pneumonia) in older adults [28]. A multisite study in the United States suggested RV as the most common single cause of community-acquired pneumonia hospitalizations, after systematically assessing for multiple pathogens including bacteria [29]. Another prospective study conducted among selected critically ill adults, wherein other causes could not fully explain the patients’ respiratory distress and clinical presentation, showed a viral positivity rate of 40.5%, with RV/EV being the second most frequently detected viruses (after influenza) [30].

Previously, RV was considered to cause only upper respiratory tract illnesses, but clinical and experimental studies have confirmed the role of RV in lower airway illnesses as well [29,31]. Observational studies assessing the etiological role of RV by comparing its prevalence in patients with respiratory tract infections with that in matched controls without respiratory symptoms to distinguish between asymptomatic carriage and the presence of agents causing disease showed strong evidence of attribution [32,33]. Similar to our study, several studies [10,34] demonstrated that RV/EV infections were most frequently associated with hospitalizations in older adults; however, these studies were not able to distinguish the contribution of each virus. It is important to note that some patients with “viral-only” pathogens identified in specimens from their upper respiratory tract may also have bacterial infection, which was not microbiologically recognized in our study, leading to a possible inflated viral attribution. Also, some detections of viral pathogens might represent a previous or resolved virus infection rather than actual disease etiology. These aspects deserve consideration while interpreting our results. The incidence of hospitalizations for those aged ≥75 years was the highest, for each season and subgroup studies. The incidence of hospitalizations in older adults might be underestimated, because older adults are less likely to be tested and diagnosed for respiratory viruses than children [35,36], as this age group may present with atypical symptoms (e.g., confusion, anorexia, dizziness, and falls) [37,38], adding to the challenges of etiological studies among these patient populations.

The landscape of respiratory virus prevention has expanded significantly in recent years. Annual influenza vaccination has been a longstanding recommendation and licensed SARS-CoV-2 and RSV vaccines are now available for adults [5,13], both vaccines were not available at the time of this study. In Spain, the Ministry of Health recommends influenza vaccination for individuals aged ≥65 years, though some regions such as Catalonia have lowered the threshold to 60 years. Despite these recommendations, the recent influenza vaccination coverage in Spain has reached about 65% [39], falling short of the 75% target for this age group [40]. Influenza vaccination remains the most effective preventive measure to avoid influenza disease and related complications [41]. In a recent review article, influenza vaccine effectiveness among various observational studies ranged from 7.2% to 89.8% against laboratory-confirmed influenza [42]. Despite the wide range in vaccine effectiveness, evidence suggests that vaccinated individuals with breakthrough infection (influenza infection among vaccinated people) are less likely to develop severe complications and die from influenza [43,44]. The RSV vaccines are now recommended for adults aged ≥75 years. Early data from the 2023–24 season in the United States indicate a 75% vaccine effectiveness against RSV-associated hospitalizations in this age group [45]. Healthcare providers and public health officials should strongly encourage the uptake of these respiratory virus vaccinations among older adults. This approach represents a crucial public health strategy to reduce the burden of influenza, RSV, and COVID-19, offering the best individual-level protection against severe disease outcomes.

The concept of a comprehensive “respiratory vaccine” to protect vulnerable populations is gaining traction [46,47], and ongoing research includes the development of an HMPV vaccine for older adults [48]. Given the multiple viruses contributing to healthcare utilization during the typical winter respiratory season, a vaccine offering broad protection against multiple pathogens would be invaluable for both individuals and society. While age indications and target populations for these vaccines may vary, it is crucial to consider the impact of other respiratory viruses, especially RV, on hospitalizations both during and outside the respiratory season. This would be particularly important when considering the duration of protection expected from a multi-pathogen vaccine including RV. Furthermore, an RV vaccine could be especially beneficial for patients with chronic obstructive pulmonary disease or asthma conditions often triggered or exacerbated by RV infections [6,7,9]. However, the high molecular diversity of RV and limited data on the contribution of different species and subtypes to clinical presentations and their relevance for specific risk groups pose considerable obstacles [49]. Overcoming these challenges will require continued research and innovative approaches in vaccine development.

Our study has limitations. Our data might not capture hospitalizations associated with virus infections that presented without respiratory signs and symptoms (e.g., cardiac hospitalizations triggered by viral infections), which might be disproportionally more represented among older patients because of the prevalence of chronic medical conditions. Patients directly admitted to the ICU might have been missed because their consent could not be obtained. A year-round surveillance could have led to a better ascertainment of these virus-related hospitalizations because RV/EV, adenovirus, bocavirus, and HMPV can be detected outside the respiratory season [8]. Our multiplex RT-PCR assay was enhanced to detect RV, but we expected that some EV may have been misclassified as RV. The differentiation of the two groups of viruses would need to be done by sequencing to fully understand the contribution of RV to hospitalizations during the respiratory season. Nonetheless, a study differentiating RV and EV has reported that ≥60% of RV/EV positives are confirmed as RV after further viral sequencing and characterization [14], which should be especially true in the fall months when RV circulation peaks [15]. Further work differentiating RV from EV by sequencing and speciation are warranted to better understand related clinical presentations and outcomes in this population. Finally, our results may not be generalizable as healthcare utilization and admission criteria may differ in other geographic settings.

Conclusions

The impact of respiratory viruses on hospitalizations among older adults warrants careful consideration while designing interventions to alleviate the burden on the healthcare system, particularly for those aged ≥75 years. Enhanced diagnostic capabilities would enable effective infection-control measures and the development of informed next-generation preventive strategies, including vaccines and therapies. Such a comprehensive approach would not only improve individual patient outcomes but also strengthen the resilience of the healthcare system during respiratory virus seasons.

Supporting information

S1 Table. Demographic characteristics of patients aged ≥50 years hospitalized because of respiratory illness and detected virus, by study year in Valencia, Spain during 2014–20.

https://doi.org/10.1371/journal.pone.0347659.s001

(DOCX)

S2 Table. Mean seasonal hospitalization rates per 100,000 individuals aged ≥50 years, by age group and detection of respiratory viruses during respiratory season in Valencia, Spain during 2014–20.

https://doi.org/10.1371/journal.pone.0347659.s002

(DOCX)

Acknowledgments

The authors express their gratitude to the field researchers of the VAHNSI network for their diligent efforts in data acquisition and thank all patients and families for their participation in the study. Valencia Hospital Surveillance Network for the Study of Influenza and Other Respiratory Viruses (VAHNSI) additional members include Maria del Carmen Otero Reigada (Hospital La Fe, Valencia, Spain); Vicente Gil Guillén (Cátedra de Medicina de Familia, Departamento de Medicina Clínica, Universidad Miguel Hernández, San Juan, Alicante, Spain; Hospital General de Elda, Elda, Spain), Ramón Limón Ramírez (Hospital de La Plana, Vila-real, Spain), Empar Carbonell Franco (Hospital Arnau de Vilanova, Valencia, Spain), Angel Belenguer Varea (Hospital de La Ribera, Alzira, Valencia, Spain), Concepción Carratalá Munuera (Hospital de San Juan, Alicante, Spain; Cátedra de Medicina de Familia, Departamento de Medicina Clínica, Universidad Miguel Hernández, San Juan, Alicante, Spain) and José Vicente Tuells Hernández (Hospital Universitario del Vinalopó, Elche, Spain). The lead for VAHNSI group is Alejandro Orrico-Sánchez (alejandro.orrico@fisabio.es).

References

1. Collaborators GLRI. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18(11):1191–210.
- View Article
- Google Scholar
2. Eurostat. Respiratory diseases statistics. Cited 2025 May 19. https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Respiratory_diseases_statistics
3. Booth A, Reed AB, Ponzo S, Yassaee A, Aral M, Plans D, et al. Population risk factors for severe disease and mortality in COVID-19: a global systematic review and meta-analysis. PLoS One. 2021;16(3):e0247461. pmid:33661992
- View Article
- PubMed/NCBI
- Google Scholar
4. Cilloniz C, Luna CM, Hurtado JC, Marcos MÁ, Torres A. Respiratory viruses: their importance and lessons learned from COVID-19. Eur Respir Rev. 2022;31(166):220051. pmid:36261158
- View Article
- PubMed/NCBI
- Google Scholar
5. Wildenbeest JG, Lowe DM, Standing JF, Butler CC. Respiratory syncytial virus infections in adults: a narrative review. Lancet Respir Med. 2024;12(10):822–36. pmid:39265602
- View Article
- PubMed/NCBI
- Google Scholar
6. Greenberg SB. Respiratory consequences of rhinovirus infection. Arch Intern Med. 2003;163(3):278–84. pmid:12578507
- View Article
- PubMed/NCBI
- Google Scholar
7. Hayashi Y, Sada M, Shirai T, Okayama K, Kimura R, Kondo M, et al. Rhinovirus Infection and virus-induced asthma. Viruses. 2022;14(12):2616. pmid:36560620
- View Article
- PubMed/NCBI
- Google Scholar
8. Moriyama M, Hugentobler WJ, Iwasaki A. Seasonality of respiratory viral infections. Annu Rev Virol. 2020;7(1):83–101. pmid:32196426
- View Article
- PubMed/NCBI
- Google Scholar
9. Romero-Tapia S de J, Guzmán Priego CG, Del-Río-Navarro BE, Sánchez-Solis M. Advances in the relationship between respiratory viruses and asthma. J Clin Med. 2023;12(17):5501. pmid:37685567
- View Article
- PubMed/NCBI
- Google Scholar
10. Bénézit F, Loubet P, Galtier F, Pronier C, Lenzi N, Lesieur Z, et al. Non-influenza respiratory viruses in adult patients admitted with influenza-like illness: a 3-year prospective multicenter study. Infection. 2020;48(4):489–95. pmid:32056143
- View Article
- PubMed/NCBI
- Google Scholar
11. Gilca R, Amini R, Carazo S, Doggui R, Frenette C, Boivin G, et al. The changing landscape of respiratory viruses contributing to hospitalizations in Quebec, Canada: results from an active hospital-based surveillance study. JMIR Public Health Surveill. 2024;10:e40792. pmid:38709551
- View Article
- PubMed/NCBI
- Google Scholar
12. Meseko C, Sanicas M, Asha K, Sulaiman L, Kumar B. Antiviral options and therapeutics against influenza: history, latest developments and future prospects. Front Cell Infect Microbiol. 2023;13:1269344. pmid:38094741
- View Article
- PubMed/NCBI
- Google Scholar
13. Brady DK, Gurijala AR, Huang L, Hussain AA, Lingan AL, Pembridge OG, et al. A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection. FEBS J. 2024;291(8):1632–62. pmid:36266238
- View Article
- PubMed/NCBI
- Google Scholar
14. Andrés C, Piñana M, Vila J, Esperalba J, Trejo-Zahínos J, Codina MG, et al. The high genetic similarity between rhinoviruses and enteroviruses remains as a pitfall for molecular diagnostic tools: a three-year overview. Infect Genet Evol. 2019;75:103996. pmid:31401308
- View Article
- PubMed/NCBI
- Google Scholar
15. Berginc N, Sočan M, Prosenc Trilar K, Petrovec M. Seasonality and genotype diversity of human rhinoviruses during an eight-year period in Slovenia. Microorganisms. 2024;12(2):341. pmid:38399745
- View Article
- PubMed/NCBI
- Google Scholar
16. Monto AS. The seasonality of rhinovirus infections and its implications for clinical recognition. Clin Ther. 2002;24(12):1987–97. pmid:12581541
- View Article
- PubMed/NCBI
- Google Scholar
17. Puig-Barberà J, Tormos A, Sominina A, Burtseva E, Launay O, Ciblak MA, et al. First-year results of the global influenza hospital surveillance network: 2012-2013 Northern hemisphere influenza season. BMC Public Health. 2014;14:564. pmid:24903737
- View Article
- PubMed/NCBI
- Google Scholar
18. Casalegno JS, Eibach D, Valette M, Enouf V, Daviaud I, Behillil S. Performance of influenza case definitions for influenza community surveillance: based on the French influenza surveillance network GROG, 2009-2014. Euro Surveill. 2017;22(14):30504.
- View Article
- Google Scholar
19. Tapparel C, Cordey S, Van Belle S, Turin L, Lee W-M, Regamey N, et al. New molecular detection tools adapted to emerging rhinoviruses and enteroviruses. J Clin Microbiol. 2009;47(6):1742–9. pmid:19339471
- View Article
- PubMed/NCBI
- Google Scholar
20. Kamau E, Agoti CN, Lewa CS, Oketch J, Owor BE, Otieno GP, et al. Recent sequence variation in probe binding site affected detection of respiratory syncytial virus group B by real-time RT-PCR. J Clin Virol. 2017;88:21–5. pmid:28107671
- View Article
- PubMed/NCBI
- Google Scholar
21. Zimmerman RK, Balasubramani GK, D’Agostino HEA, Clarke L, Yassin M, Middleton DB, et al. Population-based hospitalization burden estimates for respiratory viruses, 2015-2019. Influenza Other Respir Viruses. 2022;16(6):1133–40. pmid:35996836
- View Article
- PubMed/NCBI
- Google Scholar
22. Ciotti M, Maurici M, Santoro V, Coppola L, Sarmati L, De Carolis G, et al. Viruses of respiratory tract: an observational retrospective study on hospitalized patients in Rome, Italy. Microorganisms. 2020;8(4):501. pmid:32244685
- View Article
- PubMed/NCBI
- Google Scholar
23. Sundell N, Andersson L-M, Brittain-Long R, Sundvall P-D, Alsiö Å, Lindh M, et al. PCR detection of respiratory pathogens in asymptomatic and symptomatic adults. J Clin Microbiol. 2019;57(1):e00716-18. pmid:30355759
- View Article
- PubMed/NCBI
- Google Scholar
24. Debes S, Haug JB, de Blasio BF, Lindstrøm JC, Jonassen CM, Dudman SG. Clinical outcome of viral respiratory tract infections in hospitalized adults in Norway: high degree of inflammation and need of emergency care for cases with respiratory syncytial virus. Front Med (Lausanne). 2022;9:866494. pmid:35572955
- View Article
- PubMed/NCBI
- Google Scholar
25. Sberna G, Lalle E, Valli MB, Bordi L, Garbuglia AR, Amendola A. Changes in the circulation of common respiratory pathogens among hospitalized patients with influenza-like illnesses in the Lazio region (Italy) during fall season of the past three years. Int J Environ Res Public Health. 2022;19(10):5962. pmid:35627498
- View Article
- PubMed/NCBI
- Google Scholar
26. Petrie JG, Lauring AS, Martin ET, Kaye KS. Hospital associated respiratory virus infection in children and adults: it does not just occur during cold and flu season. Open Forum Infect Dis. 2020;7(6):ofaa200. pmid:32617374
- View Article
- PubMed/NCBI
- Google Scholar
27. Boon H, Meinders A-J, van Hannen EJ, Tersmette M, Schaftenaar E. Comparative analysis of mortality in patients admitted with an infection with influenza A/B virus, respiratory syncytial virus, rhinovirus, metapneumovirus or SARS-CoV-2. Influenza Other Respir Viruses. 2024;18(1):e13237. pmid:38249443
- View Article
- PubMed/NCBI
- Google Scholar
28. Alimi Y, Lim WS, Lansbury L, Leonardi-Bee J, Nguyen-Van-Tam JS. Systematic review of respiratory viral pathogens identified in adults with community-acquired pneumonia in Europe. J Clin Virol. 2017;95:26–35. pmid:28837859
- View Article
- PubMed/NCBI
- Google Scholar
29. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373(5):415–27. pmid:26172429
- View Article
- PubMed/NCBI
- Google Scholar
30. Cia C-T, Lin I-T, Lee J-C, Tsai H-P, Wang J-R, Ko W-C. Respiratory viral infections in pragmatically selected adults in intensive care units. Sci Rep. 2021;11(1):20058. pmid:34625621
- View Article
- PubMed/NCBI
- Google Scholar
31. Mallia P, Message SD, Gielen V, Contoli M, Gray K, Kebadze T, et al. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am J Respir Crit Care Med. 2011;183(6):734–42. pmid:20889904
- View Article
- PubMed/NCBI
- Google Scholar
32. Milucky J, Pondo T, Gregory CJ, Iuliano D, Chaves SS, McCracken J. The epidemiology and estimated etiology of pathogens detected from the upper respiratory tract of adults with severe acute respiratory infections in multiple countries, 2014-2015. PLoS One. 2020;15(10):e0240309.
- View Article
- Google Scholar
33. Shi T, Arnott A, Semogas I, Falsey AR, Openshaw P, Wedzicha JA, et al. The etiological role of common respiratory viruses in acute respiratory infections in older adults: a systematic review and meta-analysis. J Infect Dis. 2020;222(Supplement_7):S563–9. pmid:30849176
- View Article
- PubMed/NCBI
- Google Scholar
34. Sieling WD, Goldman CR, Oberhardt M, Phillips M, Finelli L, Saiman L. Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York City. Influenza Other Respir Viruses. 2021;15(5):670–7. pmid:33501772
- View Article
- PubMed/NCBI
- Google Scholar
35. Miller EK, Linder J, Kraft D, Johnson M, Lu P, Saville BR, et al. Hospitalizations and outpatient visits for rhinovirus-associated acute respiratory illness in adults. J Allergy Clin Immunol. 2016;137(3):734-43.e1. pmid:26255695
- View Article
- PubMed/NCBI
- Google Scholar
36. Zheng Z, Warren JL, Shapiro ED, Pitzer VE, Weinberger DM. Estimated incidence of respiratory hospitalizations attributable to RSV infections across age and socioeconomic groups. Pneumonia (Nathan). 2022;14(1):6. pmid:36280891
- View Article
- PubMed/NCBI
- Google Scholar
37. Falsey AR, McElhaney JE, Beran J, van Essen GA, Duval X, Esen M, et al. Respiratory syncytial virus and other respiratory viral infections in older adults with moderate to severe influenza-like illness. J Infect Dis. 2014;209(12):1873–81. pmid:24482398
- View Article
- PubMed/NCBI
- Google Scholar
38. Talbot HK, Falsey AR. The diagnosis of viral respiratory disease in older adults. Clin Infect Dis. 2010;50(5):747–51. pmid:20121411
- View Article
- PubMed/NCBI
- Google Scholar
39. European Centre for Disease Prevention and Control ECDC. Survey report on national seasonal influenza vaccination recommendations and coverage rates in EU/EEA countries. https://www.ecdc.europa.eu/en/publications-data/survey-report-national-seasonal-influenza-vaccination-recommendations
40. Council recommendation of 22 December 2009 on seasonal influenza vaccination (text with EEA relevance). 2009. https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:348:0071:0072:EN:PDF
41. Mora T, Martínez-Marcos M, Cabezas-Peña C. The influenza vaccination’s impact elderly’s health outcomes in Catalonia (Spain). Health Policy. 2025;151:105213. pmid:39561552
- View Article
- PubMed/NCBI
- Google Scholar
42. Moa A, Kunasekaran M, Akhtar Z, Costantino V, MacIntyre CR. Systematic review of influenza vaccine effectiveness against laboratory-confirmed influenza among older adults living in aged care facilities. Hum Vaccin Immunother. 2023;19(3):2271304.
- View Article
- Google Scholar
43. Arriola C, Garg S, Anderson EJ, Ryan PA, George A, Zansky SM, et al. Influenza vaccination modifies disease severity among community-dwelling adults hospitalized with influenza. Clin Infect Dis. 2017;65(8):1289–97. pmid:28525597
- View Article
- PubMed/NCBI
- Google Scholar
44. Chaves SS, Naeger S, Lounaci K, Zuo Y, Loiacono MM, Pilard Q, et al. High-dose influenza vaccine is associated with reduced mortality among older adults with breakthrough influenza even when there is poor vaccine-strain match. Clin Infect Dis. 2023;77(7):1032–42. pmid:37247308
- View Article
- PubMed/NCBI
- Google Scholar
45. Surie D, Self WH, Zhu Y, Yuengling KA, Johnson CA, Grijalva CG, et al. RSV vaccine effectiveness against hospitalization among US adults 60 years and older. JAMA. 2024;332(13):1105–7. pmid:39230920
- View Article
- PubMed/NCBI
- Google Scholar
46. Tan CW, Valkenburg SA, Poon LLM, Wang L-F. Broad-spectrum pan-genus and pan-family virus vaccines. Cell Host Microbe. 2023;31(6):902–16. pmid:37321173
- View Article
- PubMed/NCBI
- Google Scholar
47. Whitaker JA, Sahly HME, Healy CM. mRNA vaccines against respiratory viruses. Curr Opin Infect Dis. 2023;36(5):385–93. pmid:37462930
- View Article
- PubMed/NCBI
- Google Scholar
48. Krüger N, Laufer SA, Pillaiyar T. An overview of progress in human metapneumovirus (hMPV) research: structure, function, and therapeutic opportunities. Drug Discov Today. 2025;30(5):104364. pmid:40286981
- View Article
- PubMed/NCBI
- Google Scholar
49. Esneau C, Duff AC, Bartlett NW. Understanding rhinovirus circulation and impact on illness. Viruses. 2022;14(1):141. pmid:35062345
- View Article
- PubMed/NCBI
- Google Scholar

[ref1] 1. Collaborators GLRI. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18(11):1191–210.
View Article
Google Scholar

[2] View Article

[3] Google Scholar

[ref2] 2. Eurostat. Respiratory diseases statistics. Cited 2025 May 19. https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Respiratory_diseases_statistics

[ref3] 3. Booth A, Reed AB, Ponzo S, Yassaee A, Aral M, Plans D, et al. Population risk factors for severe disease and mortality in COVID-19: a global systematic review and meta-analysis. PLoS One. 2021;16(3):e0247461. pmid:33661992
View Article
PubMed/NCBI
Google Scholar

[6] View Article

[7] PubMed/NCBI

[8] Google Scholar

[ref4] 4. Cilloniz C, Luna CM, Hurtado JC, Marcos MÁ, Torres A. Respiratory viruses: their importance and lessons learned from COVID-19. Eur Respir Rev. 2022;31(166):220051. pmid:36261158
View Article
PubMed/NCBI
Google Scholar

[10] View Article

[11] PubMed/NCBI

[12] Google Scholar

[ref5] 5. Wildenbeest JG, Lowe DM, Standing JF, Butler CC. Respiratory syncytial virus infections in adults: a narrative review. Lancet Respir Med. 2024;12(10):822–36. pmid:39265602
View Article
PubMed/NCBI
Google Scholar

[14] View Article

[15] PubMed/NCBI

[16] Google Scholar

[ref6] 6. Greenberg SB. Respiratory consequences of rhinovirus infection. Arch Intern Med. 2003;163(3):278–84. pmid:12578507
View Article
PubMed/NCBI
Google Scholar

[18] View Article

[19] PubMed/NCBI

[20] Google Scholar

[ref7] 7. Hayashi Y, Sada M, Shirai T, Okayama K, Kimura R, Kondo M, et al. Rhinovirus Infection and virus-induced asthma. Viruses. 2022;14(12):2616. pmid:36560620
View Article
PubMed/NCBI
Google Scholar

[22] View Article

[23] PubMed/NCBI

[24] Google Scholar

[ref8] 8. Moriyama M, Hugentobler WJ, Iwasaki A. Seasonality of respiratory viral infections. Annu Rev Virol. 2020;7(1):83–101. pmid:32196426
View Article
PubMed/NCBI
Google Scholar

[26] View Article

[27] PubMed/NCBI

[28] Google Scholar

[ref9] 9. Romero-Tapia S de J, Guzmán Priego CG, Del-Río-Navarro BE, Sánchez-Solis M. Advances in the relationship between respiratory viruses and asthma. J Clin Med. 2023;12(17):5501. pmid:37685567
View Article
PubMed/NCBI
Google Scholar

[30] View Article

[31] PubMed/NCBI

[32] Google Scholar

[ref10] 10. Bénézit F, Loubet P, Galtier F, Pronier C, Lenzi N, Lesieur Z, et al. Non-influenza respiratory viruses in adult patients admitted with influenza-like illness: a 3-year prospective multicenter study. Infection. 2020;48(4):489–95. pmid:32056143
View Article
PubMed/NCBI
Google Scholar

[34] View Article

[35] PubMed/NCBI

[36] Google Scholar

[ref11] 11. Gilca R, Amini R, Carazo S, Doggui R, Frenette C, Boivin G, et al. The changing landscape of respiratory viruses contributing to hospitalizations in Quebec, Canada: results from an active hospital-based surveillance study. JMIR Public Health Surveill. 2024;10:e40792. pmid:38709551
View Article
PubMed/NCBI
Google Scholar

[38] View Article

[39] PubMed/NCBI

[40] Google Scholar

[ref12] 12. Meseko C, Sanicas M, Asha K, Sulaiman L, Kumar B. Antiviral options and therapeutics against influenza: history, latest developments and future prospects. Front Cell Infect Microbiol. 2023;13:1269344. pmid:38094741
View Article
PubMed/NCBI
Google Scholar

[42] View Article

[43] PubMed/NCBI

[44] Google Scholar

[ref13] 13. Brady DK, Gurijala AR, Huang L, Hussain AA, Lingan AL, Pembridge OG, et al. A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection. FEBS J. 2024;291(8):1632–62. pmid:36266238
View Article
PubMed/NCBI
Google Scholar

[46] View Article

[47] PubMed/NCBI

[48] Google Scholar

[ref14] 14. Andrés C, Piñana M, Vila J, Esperalba J, Trejo-Zahínos J, Codina MG, et al. The high genetic similarity between rhinoviruses and enteroviruses remains as a pitfall for molecular diagnostic tools: a three-year overview. Infect Genet Evol. 2019;75:103996. pmid:31401308
View Article
PubMed/NCBI
Google Scholar

[50] View Article

[51] PubMed/NCBI

[52] Google Scholar

[ref15] 15. Berginc N, Sočan M, Prosenc Trilar K, Petrovec M. Seasonality and genotype diversity of human rhinoviruses during an eight-year period in Slovenia. Microorganisms. 2024;12(2):341. pmid:38399745
View Article
PubMed/NCBI
Google Scholar

[54] View Article

[55] PubMed/NCBI

[56] Google Scholar

[ref16] 16. Monto AS. The seasonality of rhinovirus infections and its implications for clinical recognition. Clin Ther. 2002;24(12):1987–97. pmid:12581541
View Article
PubMed/NCBI
Google Scholar

[58] View Article

[59] PubMed/NCBI

[60] Google Scholar

[ref17] 17. Puig-Barberà J, Tormos A, Sominina A, Burtseva E, Launay O, Ciblak MA, et al. First-year results of the global influenza hospital surveillance network: 2012-2013 Northern hemisphere influenza season. BMC Public Health. 2014;14:564. pmid:24903737
View Article
PubMed/NCBI
Google Scholar

[62] View Article

[63] PubMed/NCBI

[64] Google Scholar

[ref18] 18. Casalegno JS, Eibach D, Valette M, Enouf V, Daviaud I, Behillil S. Performance of influenza case definitions for influenza community surveillance: based on the French influenza surveillance network GROG, 2009-2014. Euro Surveill. 2017;22(14):30504.
View Article
Google Scholar

[66] View Article

[67] Google Scholar

[ref19] 19. Tapparel C, Cordey S, Van Belle S, Turin L, Lee W-M, Regamey N, et al. New molecular detection tools adapted to emerging rhinoviruses and enteroviruses. J Clin Microbiol. 2009;47(6):1742–9. pmid:19339471
View Article
PubMed/NCBI
Google Scholar

[69] View Article

[70] PubMed/NCBI

[71] Google Scholar

[ref20] 20. Kamau E, Agoti CN, Lewa CS, Oketch J, Owor BE, Otieno GP, et al. Recent sequence variation in probe binding site affected detection of respiratory syncytial virus group B by real-time RT-PCR. J Clin Virol. 2017;88:21–5. pmid:28107671
View Article
PubMed/NCBI
Google Scholar

[73] View Article

[74] PubMed/NCBI

[75] Google Scholar

[ref21] 21. Zimmerman RK, Balasubramani GK, D’Agostino HEA, Clarke L, Yassin M, Middleton DB, et al. Population-based hospitalization burden estimates for respiratory viruses, 2015-2019. Influenza Other Respir Viruses. 2022;16(6):1133–40. pmid:35996836
View Article
PubMed/NCBI
Google Scholar

[77] View Article

[78] PubMed/NCBI

[79] Google Scholar

[ref22] 22. Ciotti M, Maurici M, Santoro V, Coppola L, Sarmati L, De Carolis G, et al. Viruses of respiratory tract: an observational retrospective study on hospitalized patients in Rome, Italy. Microorganisms. 2020;8(4):501. pmid:32244685
View Article
PubMed/NCBI
Google Scholar

[81] View Article

[82] PubMed/NCBI

[83] Google Scholar

[ref23] 23. Sundell N, Andersson L-M, Brittain-Long R, Sundvall P-D, Alsiö Å, Lindh M, et al. PCR detection of respiratory pathogens in asymptomatic and symptomatic adults. J Clin Microbiol. 2019;57(1):e00716-18. pmid:30355759
View Article
PubMed/NCBI
Google Scholar

[85] View Article

[86] PubMed/NCBI

[87] Google Scholar

[ref24] 24. Debes S, Haug JB, de Blasio BF, Lindstrøm JC, Jonassen CM, Dudman SG. Clinical outcome of viral respiratory tract infections in hospitalized adults in Norway: high degree of inflammation and need of emergency care for cases with respiratory syncytial virus. Front Med (Lausanne). 2022;9:866494. pmid:35572955
View Article
PubMed/NCBI
Google Scholar

[89] View Article

[90] PubMed/NCBI

[91] Google Scholar

[ref25] 25. Sberna G, Lalle E, Valli MB, Bordi L, Garbuglia AR, Amendola A. Changes in the circulation of common respiratory pathogens among hospitalized patients with influenza-like illnesses in the Lazio region (Italy) during fall season of the past three years. Int J Environ Res Public Health. 2022;19(10):5962. pmid:35627498
View Article
PubMed/NCBI
Google Scholar

[93] View Article

[94] PubMed/NCBI

[95] Google Scholar

[ref26] 26. Petrie JG, Lauring AS, Martin ET, Kaye KS. Hospital associated respiratory virus infection in children and adults: it does not just occur during cold and flu season. Open Forum Infect Dis. 2020;7(6):ofaa200. pmid:32617374
View Article
PubMed/NCBI
Google Scholar

[97] View Article

[98] PubMed/NCBI

[99] Google Scholar

[ref27] 27. Boon H, Meinders A-J, van Hannen EJ, Tersmette M, Schaftenaar E. Comparative analysis of mortality in patients admitted with an infection with influenza A/B virus, respiratory syncytial virus, rhinovirus, metapneumovirus or SARS-CoV-2. Influenza Other Respir Viruses. 2024;18(1):e13237. pmid:38249443
View Article
PubMed/NCBI
Google Scholar

[101] View Article

[102] PubMed/NCBI

[103] Google Scholar

[ref28] 28. Alimi Y, Lim WS, Lansbury L, Leonardi-Bee J, Nguyen-Van-Tam JS. Systematic review of respiratory viral pathogens identified in adults with community-acquired pneumonia in Europe. J Clin Virol. 2017;95:26–35. pmid:28837859
View Article
PubMed/NCBI
Google Scholar

[105] View Article

[106] PubMed/NCBI

[107] Google Scholar

[ref29] 29. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373(5):415–27. pmid:26172429
View Article
PubMed/NCBI
Google Scholar

[109] View Article

[110] PubMed/NCBI

[111] Google Scholar

[ref30] 30. Cia C-T, Lin I-T, Lee J-C, Tsai H-P, Wang J-R, Ko W-C. Respiratory viral infections in pragmatically selected adults in intensive care units. Sci Rep. 2021;11(1):20058. pmid:34625621
View Article
PubMed/NCBI
Google Scholar

[113] View Article

[114] PubMed/NCBI

[115] Google Scholar

[ref31] 31. Mallia P, Message SD, Gielen V, Contoli M, Gray K, Kebadze T, et al. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am J Respir Crit Care Med. 2011;183(6):734–42. pmid:20889904
View Article
PubMed/NCBI
Google Scholar

[117] View Article

[118] PubMed/NCBI

[119] Google Scholar

[ref32] 32. Milucky J, Pondo T, Gregory CJ, Iuliano D, Chaves SS, McCracken J. The epidemiology and estimated etiology of pathogens detected from the upper respiratory tract of adults with severe acute respiratory infections in multiple countries, 2014-2015. PLoS One. 2020;15(10):e0240309.
View Article
Google Scholar

[121] View Article

[122] Google Scholar

[ref33] 33. Shi T, Arnott A, Semogas I, Falsey AR, Openshaw P, Wedzicha JA, et al. The etiological role of common respiratory viruses in acute respiratory infections in older adults: a systematic review and meta-analysis. J Infect Dis. 2020;222(Supplement_7):S563–9. pmid:30849176
View Article
PubMed/NCBI
Google Scholar

[124] View Article

[125] PubMed/NCBI

[126] Google Scholar

[ref34] 34. Sieling WD, Goldman CR, Oberhardt M, Phillips M, Finelli L, Saiman L. Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York City. Influenza Other Respir Viruses. 2021;15(5):670–7. pmid:33501772
View Article
PubMed/NCBI
Google Scholar

[128] View Article

[129] PubMed/NCBI

[130] Google Scholar

[ref35] 35. Miller EK, Linder J, Kraft D, Johnson M, Lu P, Saville BR, et al. Hospitalizations and outpatient visits for rhinovirus-associated acute respiratory illness in adults. J Allergy Clin Immunol. 2016;137(3):734-43.e1. pmid:26255695
View Article
PubMed/NCBI
Google Scholar

[132] View Article

[133] PubMed/NCBI

[134] Google Scholar

[ref36] 36. Zheng Z, Warren JL, Shapiro ED, Pitzer VE, Weinberger DM. Estimated incidence of respiratory hospitalizations attributable to RSV infections across age and socioeconomic groups. Pneumonia (Nathan). 2022;14(1):6. pmid:36280891
View Article
PubMed/NCBI
Google Scholar

[136] View Article

[137] PubMed/NCBI

[138] Google Scholar

[ref37] 37. Falsey AR, McElhaney JE, Beran J, van Essen GA, Duval X, Esen M, et al. Respiratory syncytial virus and other respiratory viral infections in older adults with moderate to severe influenza-like illness. J Infect Dis. 2014;209(12):1873–81. pmid:24482398
View Article
PubMed/NCBI
Google Scholar

[140] View Article

[141] PubMed/NCBI

[142] Google Scholar

[ref38] 38. Talbot HK, Falsey AR. The diagnosis of viral respiratory disease in older adults. Clin Infect Dis. 2010;50(5):747–51. pmid:20121411
View Article
PubMed/NCBI
Google Scholar

[144] View Article

[145] PubMed/NCBI

[146] Google Scholar

[ref39] 39. European Centre for Disease Prevention and Control ECDC. Survey report on national seasonal influenza vaccination recommendations and coverage rates in EU/EEA countries. https://www.ecdc.europa.eu/en/publications-data/survey-report-national-seasonal-influenza-vaccination-recommendations

[ref40] 40. Council recommendation of 22 December 2009 on seasonal influenza vaccination (text with EEA relevance). 2009. https://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:348:0071:0072:EN:PDF

[ref41] 41. Mora T, Martínez-Marcos M, Cabezas-Peña C. The influenza vaccination’s impact elderly’s health outcomes in Catalonia (Spain). Health Policy. 2025;151:105213. pmid:39561552
View Article
PubMed/NCBI
Google Scholar

[150] View Article

[151] PubMed/NCBI

[152] Google Scholar

[ref42] 42. Moa A, Kunasekaran M, Akhtar Z, Costantino V, MacIntyre CR. Systematic review of influenza vaccine effectiveness against laboratory-confirmed influenza among older adults living in aged care facilities. Hum Vaccin Immunother. 2023;19(3):2271304.
View Article
Google Scholar

[154] View Article

[155] Google Scholar

[ref43] 43. Arriola C, Garg S, Anderson EJ, Ryan PA, George A, Zansky SM, et al. Influenza vaccination modifies disease severity among community-dwelling adults hospitalized with influenza. Clin Infect Dis. 2017;65(8):1289–97. pmid:28525597
View Article
PubMed/NCBI
Google Scholar

[157] View Article

[158] PubMed/NCBI

[159] Google Scholar

[ref44] 44. Chaves SS, Naeger S, Lounaci K, Zuo Y, Loiacono MM, Pilard Q, et al. High-dose influenza vaccine is associated with reduced mortality among older adults with breakthrough influenza even when there is poor vaccine-strain match. Clin Infect Dis. 2023;77(7):1032–42. pmid:37247308
View Article
PubMed/NCBI
Google Scholar

[161] View Article

[162] PubMed/NCBI

[163] Google Scholar

[ref45] 45. Surie D, Self WH, Zhu Y, Yuengling KA, Johnson CA, Grijalva CG, et al. RSV vaccine effectiveness against hospitalization among US adults 60 years and older. JAMA. 2024;332(13):1105–7. pmid:39230920
View Article
PubMed/NCBI
Google Scholar

[165] View Article

[166] PubMed/NCBI

[167] Google Scholar

[ref46] 46. Tan CW, Valkenburg SA, Poon LLM, Wang L-F. Broad-spectrum pan-genus and pan-family virus vaccines. Cell Host Microbe. 2023;31(6):902–16. pmid:37321173
View Article
PubMed/NCBI
Google Scholar

[169] View Article

[170] PubMed/NCBI

[171] Google Scholar

[ref47] 47. Whitaker JA, Sahly HME, Healy CM. mRNA vaccines against respiratory viruses. Curr Opin Infect Dis. 2023;36(5):385–93. pmid:37462930
View Article
PubMed/NCBI
Google Scholar

[173] View Article

[174] PubMed/NCBI

[175] Google Scholar

[ref48] 48. Krüger N, Laufer SA, Pillaiyar T. An overview of progress in human metapneumovirus (hMPV) research: structure, function, and therapeutic opportunities. Drug Discov Today. 2025;30(5):104364. pmid:40286981
View Article
PubMed/NCBI
Google Scholar

[177] View Article

[178] PubMed/NCBI

[179] Google Scholar

[ref49] 49. Esneau C, Duff AC, Bartlett NW. Understanding rhinovirus circulation and impact on illness. Viruses. 2022;14(1):141. pmid:35062345
View Article
PubMed/NCBI
Google Scholar

[181] View Article

[182] PubMed/NCBI

[183] Google Scholar

Figures

Abstract

Background

Methods

Results

Conclusions

Introduction

Materials and methods

Study setting and design

Case definition and enrollment

Data collection

Laboratory methods

Statistical analyses

Ethics declaration

Results

Demographic characteristics and underlying medical conditions

Time-dependent variation on virus detection

Severity of hospitalization by virus type

Incidence rate

Discussion

Conclusions

Supporting information

S1 Table. Demographic characteristics of patients aged ≥50 years hospitalized because of respiratory illness and detected virus, by study year in Valencia, Spain during 2014–20.

S2 Table. Mean seasonal hospitalization rates per 100,000 individuals aged ≥50 years, by age group and detection of respiratory viruses during respiratory season in Valencia, Spain during 2014–20.

Acknowledgments

References