Hong Kong Med J 2024 Jun;30(3):196–9 | Epub 29 May 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
EDITORIAL
Bridging the gap in the prevention of respiratory syncytial virus infection among older adults in Hong Kong
Ivan FN Hung, MD (HK), FRCP (Lond)1,2 Ada WC Lin, FHKAM (Medicine), FHKCCM3; Jane CK Chan, MD, PDipID4; Tony NH Chan, FHKAM (Medicine), FRCP (Edin)5; Philip Eng, MMed, FRCP (Lond)6,7; Angus HY Lo, FHKAM (Medicine), FRCP (Edin)8; Martin CS Wong, MD, MPH9,10; William KK Wong, FHKAM (Medicine), FRCP (Edin)5
1 Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
2 Gleneagles Hospital Hong Kong, Hong Kong SAR, China
3 HKSH Medical Group, Hong Kong SAR, China
4 Hong Kong Chinese Medical Association, Hong Kong SAR, China
5 The Hong Kong Geriatrics Society, Hong Kong SAR, China
6 Mount Elizabeth Hospital, Singapore
7 National University of Singapore, Singapore
8 Premier Medical Centre, Hong Kong SAR, China
9 The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
10 Editor-in-Chief, Hong Kong Medical Journal
Corresponding author: Dr Ivan FN Hung (ivanhung@hku.hk)
Respiratory syncytial virus (RSV) is an important
pathogen that causes acute respiratory tract illness
and exacerbations of chronic cardiopulmonary
disease among adults.1 2 3 Although most RSV
infections in adults are mild, advanced age, chronic
cardiopulmonary disease, and immunocompromising
conditions can predispose individuals to higher risks
of morbidity and mortality.1 3 4 Respiratory syncytial
virus will become an increasingly important threat
to countries/regions with an ageing population, such
as Hong Kong. In 2046, older persons are projected
to constitute 36% of Hong Kong’s total population,5
underscoring the need to better understand the RSV
disease burden to protect this vulnerable population.
Respiratory syncytial virus disease burden in older adults is substantial but often underestimated
Respiratory syncytial virus is a major cause of
morbidity and mortality in older adults. In 2019,
adults aged >70 years had the highest worldwide
mortality rate of 34.5 per 100 000 individuals.5
Recent studies have shown that, in older adults,
RSV causes more severe infections than influenza.6 7
Older patients hospitalised for RSV have longer
hospital stays, higher risks of pneumonia and
bacterial superinfection, a higher risk of intensive
care unit admission, a greater likelihood of repeat
hospitalisation, and higher in-hospital and 1-year
mortality rates than older patients hospitalised for
influenza.6 7
Respiratory syncytial virus infection imposes
a substantial economic burden on older adults. In the United States, the national direct cost of RSV-related
hospitalisations among adults aged ≥60 years
was estimated to be US$1.5 to 4.0 billion in 2005.8
Furthermore, severe RSV can cause functional
decline and insidious deterioration of respiratory
health, along with high mortality, in frail older
adults.9 10 11 12 Exacerbations of congestive heart failure and other chronic conditions can substantially
contribute to disease burden among older adults.3 13
Changes in respiratory syncytial virus seasonality can hinder reduction of its disease burden
Respiratory syncytial virus circulation is seasonal,
typically peaking between April and November in
Hong Kong.14 An understanding of RSV seasonality
can facilitate effective public health planning and
resource allocation. However, disruptions in RSV
seasonality could lead to off-season outbreaks that
affect health system performance.14 For example, the
implementation of infection control measures during
the coronavirus disease 2019 pandemic
and their subsequent relaxation has led to an atypical
surge in RSV activity across many countries in the
post–coronavirus disease 2019 era,15 16 17 highlighting the need for
year-long disease surveillance.
Existing challenges that lead to the underestimation of respiratory syncytial virus burden in older adults
Respiratory syncytial virus infection is challenging to diagnose because of its non-specific clinical symptoms.14 18 Although rapid antigen diagnostic
tests and nucleic acid amplification tests are
important tools for RSV detection, their diagnostic
accuracy in adults is generally poor due to the lower
viral load in such patients, especially when upper
respiratory tract specimens are used for testing.9 18 19
Therefore, clinicians must be aware of the limitations
of current assays while supporting the development
of more sensitive assays for adults.
Additionally, the testing rate among adult
patients remains suboptimal,14 resulting in
underdiagnosis of RSV infection. The absence of
disease surveillance protocols and lack of systemic
data collection mechanisms lead to further
underestimation of the RSV disease burden in Hong
Kong.14 Currently, RSV is not one of the statutory
notifiable infectious diseases according to the Centre
for Health Protection.14 A surveillance system that
allows clinicians to submit data regarding positive
RSV cases would be helpful in terms of monitoring
its incidence and disease burden.
A safe and effective vaccine is needed to reduce respiratory syncytial virus disease burden
The current approach to managing RSV infection
in adults focuses on supportive care.3 Whereas
immunoprophylaxis with monoclonal antibodies is
recommended for infants and young children, there
are no clinical data supporting these treatments for
high-risk adults.3 In the absence of guideline-directed
management, some clinicians do not recommend
RSV testing for adults with suspected acute lower
respiratory tract infection (ALRTI). Considering the
high RSV disease burden and lack of RSV-specific
treatment, a safe and effective vaccine is urgently
needed to prevent RSV-related severe illness among
high-risk adults.
The quest for an effective RSV vaccine began in
the 1960s and encountered multiple obstacles. The
discovery of the RSV fusion (F) glycoprotein in its
pre-F conformation has renewed interest in vaccine
development. The RSV pre-F protein (RSVpreF) has
emerged as an attractive candidate vaccine target
because of its conserved neutralising epitope.20 21
The multinational phase III RENOIR trial (RSV Vaccine Efficacy Study in Older Adults Immunized against RSV Disease) showed that the bivalent RSVpreF vaccine had
respective efficacy rates of 84.4% and 81.0% for
preventing ALRTI and medically attended RSV-associated
acute respiratory tract illness over two
RSV seasons among immunocompetent adults aged
≥60 years.22 Importantly, the RSVpreF vaccine also
demonstrated a favourable safety profile. A recent
study showed that concomitant administration of
RSVpreF and seasonal inactivated influenza vaccine
elicited robust RSV serum-neutralising responses
and appeared to have a favourable safety profile among adults aged 50 to 85 years,23 thereby supporting
annual concomitant immunisation with seasonal
inactivated influenza vaccine.
Based on the RENOIR trial, the United States
Food and Drug Administration approved bivalent
RSVpreF vaccine for use in adults aged ≥60 years.24
Subsequently (in June 2023), the United States
Centers for Disease Control and Prevention’s
Advisory Committee on Immunisation Practices
voted to recommend that adults aged ≥60 years
receive a single dose of RSV vaccine through a shared
clinical decision-making process.24
Driving the successful implementation of respiratory syncytial virus vaccination in older adults
It is important to conduct a public awareness campaign that educates the general public about the
risks of RSV infections among high-risk individuals,
especially older adults. This campaign should
address vaccine hesitancy by highlighting the safety
and efficacy of vaccines against severe RSV while
dispelling misconceptions about the safety of the
vaccine.
Additionally, it is imperative to establish a
continuous medical education programme focused
on respiratory care for primary care physicians and
other specialists who manage high-risk patients.
This programme should cover the role of diagnostic
testing in patients with suspected ALRTI to guide
disease management (despite the absence of effective
treatment) and vaccination against severe RSV
in high-risk populations. Ideally, the programme
should emphasise the public health benefits of
RSV vaccination beyond reducing disease severity.
Moreover, the programme should discuss strategies
to encourage vaccination uptake among older adults
with cognitive impairment and/or their family
members.
Additional research to improve confidence in respiratory syncytial virus vaccination
Local epidemiological studies could help to
define RSV prevalence in general and high-risk
populations, quantify the RSV disease burden, and
identify its impacts on public health and healthcare
services. These data could also aid in defining target
populations that would experience the greatest
benefit from RSV vaccination. Furthermore, a
local cost-effectiveness analysis based on local
epidemiological data could help demonstrate the
value of RSV vaccination in target populations.
Research concerning the durability of protection
conferred by an RSV vaccine in high-risk adults could guide appropriate dosing intervals and vaccination
schedules. Additional efficacy and safety data
concerning the co-administration of an RSV vaccine
with other respiratory virus vaccines could support
simplified immunisation schedules for adults.
Post-marketing studies could provide additional
information regarding the real-world effectiveness
and safety of an RSV vaccine in target populations,
especially individuals with multimorbidity and
immunocompromised conditions. Future real-world
studies could also include assessments of vaccine
effectiveness in reducing other clinical outcomes,
such as the rates of RSV infection, hospitalisation,
intensive care unit admission, ventilator use, and
mortality.
Author contributions
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
Conflicts of interest
IFN Hung is an advisory board member for Pfizer, GlaxoSmithKline,
AstraZeneca, MSD, and Moderna. P Eng served as an advisory
board member for Pfizer, GlaxoSmithKline, AstraZeneca, and Boehringer Ingelheim. MCS Wong is an honorary medical advisor for
GenieBiome Ltd, BGI Health (HK) Company Limited, and Sunrise; an advisory committee
member for Pfizer; an external expert for GlaxoSmithKline; and a member of the advisory board for AstraZeneca;
he has also been paid consultancy fees for providing research
advice. Other authors declare no conflicts of interest.
Funding/support
Funding for this study was provided by Pfizer Hong Kong. Editorial and medical writing support was provided by Weber Shandwick Health HK, funded by Pfizer Hong Kong. The funders had no role in study design, data collection/analysis/interpretation or manuscript preparation.
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