# The Silent Surge: The Underrecognized Burden of Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Viruses in Adults

Benjamin Davido, Paul Loubet

► To cite this version:

Benjamin Davido, Paul Loubet. The Silent Surge: The Underrecognized Burden of Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Viruses in Adults. International Journal of Infectious Diseases, 2025, 159, pp.108006-108006. 10.1016/j.ijid.2025.108006. hal-05301000

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Submitted on 5 Nov 2025

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## Perspective

# The silent surge: the under-recognised burden of respiratory syncytial virus, human metapneumovirus, and parainfluenza viruses in adults

<figure><img src="image_2.png" /></figure>

Benjamin Davido<sup>1,2,*</sup>, Paul Loubet<sup>3</sup>

## ARTICLE INFO

**Article history:**

Received 26 June 2025

Revised 23 July 2025

Accepted 30 July 2025

**Keywords:**

HMPV

Vaccine

Screening

Burden of disease

Silent surge

## ABSTRACT

Respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and parainfluenza viruses (PIV) drive substantial morbidity in adults, yet remain underdiagnosed due to diagnostic gaps. While influenza and COVID-19 benefit from rapid triplex antigenic tests and PCR, HMPV and PIV lack routine diagnostics, and RSV testing is underutilised in adults, leading to frequent misdiagnosis as common colds or bacterial infections. This opinion paper highlights the burden of these "forgotten viruses" in elderly and comorbid populations, where RSV and HMPV cause significant hospitalizations. Misdiagnosis fuels cardiovascular complications and antimicrobial resistance through inappropriate antibiotic use. Recent RSV vaccine successes offer a blueprint for HMPV and PIV, but improved diagnostics are critical to guide vaccine strategies and inform prevention efforts. Addressing these gaps can reduce healthcare costs and protect vulnerable populations from these hidden respiratory threats.

© 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY license

(http://creativecommons.org/licenses/by/4.0/)

## Introduction

Beneath the well-known threats of influenza, COVID-19 and respiratory syncytial virus (RSV) often overlooked in adults, lies a silent surge of lesser-recognised respiratory viruses, quietly driving significant morbidity worldwide. Respiratory tract infections (RTIs) caused by viruses such as influenza, SARS-CoV-2, and respiratory syncytial virus (RSV) peak in fall and winter, while human metapneumovirus (HMPV) and parainfluenza viruses (PIV) are more prevalent from late winter to spring [1,2]. Unlike influenza, COVID-19 and RSV, which benefit from triplex rapid antigenic tests and PCR [3], HMPV and PIV lack routine diagnostic tests and remain underdiagnosed due to limited testing outside the typical influenza season, often misdiagnosed as the common cold or a bacterial infection, resulting in underestimation of their true burden of disease (BoD) [1,2,4]. Furthermore, a retrospective study conducted between 2016 and 2019 in the United States of America concluded that RSV, hMPV, and PIV have a significant burden on hospitalised adults, even in individuals without classic risk factors [5]. This perspective argues that these diagnostic gaps, encompassing the under-recognition of RSV in adults and the underdiagnosis of HMPV and PIV, hinder effective management, particularly in elderly individuals with comorbidities. Addressing these gaps is critical to inform vaccine strategies, reduce healthcare costs, and mitigate collateral damage, including often unrecognised cardiovascular complications and antimicrobial resistance (AMR).

### Burden of disease in vulnerable populations

The BoD of RSV, HMPV, and PIV is particularly pronounced in elderly individuals with comorbidities such as chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), and diabetes [4,6]. Studies estimate that RSV causes 60,000-160,000 hospitalizations and 6000-10,000 deaths annually among adults aged ≥65 years in the United States alone [7]. HMPV is responsible for approximately 122,000 hospitalizations in older adults annually in 2019 [8]. Additionally, implementing rapid and cost-effective diagnostic tools in resource-limited settings, along with establishing comprehensive surveillance networks to monitor viral evolution and outbreak dynamics, will be essential to closing the current diagnostic gap on a global scale [9]. PIV comprises four types (1-4), with limited or no cross-protection between them, and PIV3 accounting for approximately 60% of the disease burden [10]. These viruses, including RSV and HMPV, typically exacerbate underlying

<footnote n="1"><sup>1</sup>Maladies infectieuses, Université Paris-Saclay, AP-HP Hôpital Raymond Poincaré, Garches 92380, France</footnote>

<footnote n="2"><sup>2</sup>Université Paris-Saclay, UVSQ, Montigny-Le-Bretonneux 78180, France</footnote>

<footnote n="3"><sup>3</sup>Virulence Bactérienne et Infections Chroniques, INSERM U1047, Univ Montpellier, Service des Maladies Infectieuses et Tropicales, CHU Nîmes, Nîmes 30900, France</footnote>

<footnote>* Corresponding author: B Davido, Infectious Diseases Department; Raymond-Poincaré Teaching Hospital, Garches 92380, France.</footnote>

<footnote>E-mail address: benjamin.davido@aphp.fr (B. Davido).</footnote>
conditions, notably COPD and heart failure, leading to severe out-
comes like pneumonia, bronchiolitis as reported by Shinkai et al.
[9].

The elderly with comorbidities are also heavily impacted by in-
fluenza and COVID-19, highlighting a shared vulnerability. How-
ever, the lack of routine testing for RSV, HMPV, and PIV obscures
their contribution to this burden, hindering targeted interventions.
Better understanding the BoD through improved diagnostics is es-
sential to prioritise prevention strategies, particularly for high-risk
groups.

Furthermore, misdiagnosed RTIs contribute to significant col-
lateral damage. RSV, influenza, and COVID-19 are associated with

cardiovascular complications, including myocardial infarction and
heart failure exacerbation [11]. Emerging evidence suggests HMPV
may pose similar risks, particularly in patients with chronic heart
disease [12]. These complications increase long-term morbidity
and healthcare costs, underscoring the need for accurate diagno-
sis.

Additionally, RTIs drive antibiotic resistance, as approximately 45% of antibiotic prescriptions in winter are for respiratory infections [13], with at least 20% of ambulatory care cases being viral in children [14]. Misdiagnosis of viral RTIs as bacterial infections leads to inappropriate antibiotic use, fueling AMR. For example, it has been estimated that 6.9% of COVID-19 cases involve bacterial

<figure><img src="image_3.png" /><figcaption>**Figure 1.** Overview of challenges and strategies for under-recognised respiratory viruses in adults.</figcaption></figure>
co-infections, yet antibiotics are often overprescribed due to diag-
nostic uncertainty [15]. Improved diagnostics for HMPV, RSV, and
PIV could reduce unnecessary prescriptions and help mitigate the
development of AMR.

Diagnostic disparities in ambulatory care

Diagnostic approaches for respiratory viruses vary significantly between ambulatory and hospital settings, contributing to underdiagnosis of HMPV, PIV, and RSV in adults. In ambulatory care, rapid triplex antigenic tests for influenza, COVID-19, and RSV enable quick identification and targeted treatment (e.g., oseltamivir for influenza, nirmatrelvir for COVID-19), but their moderate performance in adults, particularly for RSV (sensitivity ~44.4-66.6%) with moderate viral load (Ct <30), limits their reliability [3].

Moreover, triplex PCR on nasopharyngeal swabs combining the detection of RSV/SARS-CoV-2/Influenza has become widely used since the COVID-19 pandemic, allowing rapid diagnosis of seasonal pathogens for a reasonable price [16]. However, HMPV and PIV detection rely primarily on multiplex polymerase chain reaction (PCR) panels, confined mainly to hospital settings due to cost and infrastructure requirements [1,2,17]. This diagnostic bottleneck, exacerbated by lower suspicion of viral RTIs outside the fall/winter season, limits the ability to assess the global prevalence of these viruses in outpatient and inpatient populations, leaving their BoD underestimated.

Even in the case of RSV, despite the availability of antigenic tests, general practitioners (GPs) often overlook testing in adults, focusing instead on tests for influenza and COVID-19. This is partly due to a lack of familiarity with RSV's significance in adults compared to children, despite its substantial morbidity [18]. The overlap in clinical presentation—cough, fever, and shortness of breath—further complicates differentiation without systematic testing. As a result, RSV, HMPV, and PIV are frequently misdiagnosed, delaying appropriate management and skewing epidemiological data. Expanding access to rapid tests for HMPV [19] and PIV, alongside increased RSV testing in adults, is critical to quantify their BoD and inform vaccine strategies.

Vaccine strategies and prevention

The recent approval of three RSV vaccines—Arexvy (GSK), mRESVIA (Moderna), and Abrysvo (Pfizer)—marks a significant milestone in reducing RSV-related morbidity in adults aged ≥60 years [20]. Clinical trials and real-life data have demonstrated high efficacy against lower respiratory tract illness and RSV-related hospitalization [21–23]. These successes underscore the potential of vaccines to alleviate hospital burden and healthcare costs. For HMPV, vaccine development is gaining momentum, with ongoing studies exploring combined RSV/HMPV candidates [24] but also mRNA-based hMPV/PIV3 vaccine with safety and immunogenicity data among adults and children [25,26]. Enhanced BoD data through widespread screening could accelerate these efforts by justifying investment in HMPV vaccines.

Prevention extends beyond vaccines. Non-pharmaceutical inter-
ventions, such as hand hygiene and masking, remain critical but
are underutilised for viruses like HMPV and PIV due to low pub-
lic awareness. Raising awareness of these pathogens' impact could
strengthen adherence to preventive measures.

Conclusion

The silent surge of HMPV, RSV, and PIV demands urgent ac-
tion to close diagnostic gaps and enhance prevention (Figure 1).
The success of RSV vaccines provides a blueprint for tackling HMPV

and other pathogens, while addressing misdiagnosis can curb car-
diovascular complications and AMR. By unmasking these forgot-
ten viruses, we can protect vulnerable populations and reduce the
global burden of RTIs.

Declaration of competing interest

The authors have no competing interests to declare.

Author contributions

BD drafted the first version of the manuscript and designed the
article. PL revised it critically for important intellectual content. BD
was responsible for the Figure and citations. BD and LPL approved
the final revision of the manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval

The authors confirm that all listed authors have contributed to
this work and approved the paper.

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