Article Category: Editorial
Published Online: May 02, 2024
Page range: 195 - 201
DOI: https://doi.org/10.2478/pneum-2023-0046
Keywords
© 2022 Florin Mihaltan et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Respiratory syncytial virus (RSV) is an enveloped negative-sense, single-stranded ribonucleic acid (RNA) virus belonging to the
In Europe, RSV seasons begins in October and lasts until March. The RSV epidemic in Europe progresses rapidly at the beginning of October and the median start of the RSV season is at beginning of December. The median length of the RSV season is about 16-18 weeks, and the peak is around end of January (7). RSV is very infectious, and it can be spread through direct oral contact, respiratory droplets, or indirect exposure to the respiratory secretions of individuals who are infected (8). Although the risks of this virus were recognized in previous decades, they are now being reassessed and emphasized.
Clinical symptoms of RSV infection may vary from mild, cold-like symptoms (runny nose, coughing, sneezing, fever, wheezing and/or decrease in appetite), to severe respiratory disease (e.g., pneumonia or bronchitis) (9,10).
In older adults and in adults at high risk, RSV infection can cause serious respiratory illnesses and complications (including secondary bacterial pneumonia and influenza-like diseases) that significantly affect patient morbidity and mortality (2,12,13) and can worsen a patient’s underlying condition like congestive heart failure, chronic obstructive pulmonary disease (COPD) or asthma (15). Children and older adults and adults with certain underlying comorbidities that put them at high risk, such as immunocompromising conditions, chronic cardiopulmonary disease, renal and liver disease, and diabetes are at a higher risk of experiencing severe illness (2,11,12,17).
RSV is one of the leading causes of respiratory illness in older adults, next to influenza and COVID-19 (14). Contrary to children, who will often develop a recognizable bronchiolitis because of an RSV infection, RSV infection in adults is underrecognized.
Besides the presence of underlying comorbidities, the main factors leading to the increased burden of RSV and severe forms of disease in elderly population are ageing and immunosenescence. Pulmonary function is declining with age, compromising the natural ability to overcome infections caused by respiratory pathogens. Immunosenescence is another contributing factor, which describes the progressive dysregulation and decline of the immune system, that leads to increased susceptibility to pathogens (18,19).
RSV is associated with increased morbidity and mortality in elderly population. It is estimated that in United States of America, each year RSV causes 60,000-160,000 hospitalizations and between 6,000-10,000 deaths among adults 65 years and older (20). According to European Centre for Disease Prevention and Control (ECDC) in the EU, Norway and the United Kingdom, RSV is responsible for on average of 158 000 hospitalizations per year (21), in adult population. The rate of RSV-associated acute respiratory illness (ARI) depends on the virus seasonality, age, and comorbidities. Based on a systematic literature review, in 2015 the annual rate RSV-ARI (acute respiratory infections) in the community was estimated to be 6.7 per 1,000 persons per year (95% confidence interval [CI]: 1.4-31.5) in the older adults in industrialized countries (22). Another meta-analysis from 2022, concluded that when analyzing adult populations with comorbidities, from high-income/industrialized countries, the overall incidence of RSV-ARI was 30.3 (95%CI:15.3-59.9) per 1,000 persons per year/season, indicating a substantial burden of disease (23).
Although the burden of RSV is significant, it still remains an underdiagnosed and underreported condition in adults. Testing for RSV infection in adults is not routinely performed. The lack of specific guidelines for the diagnosis and management of RSV in adults, the low clinical awareness of RSV due to similar presentation to other respiratory illnesses, and lack of sensitivity and reporting delay of some testing modalities are the main reasons for this situation (24). Most existing RSV surveillance is conducted within the context of existing influenza surveillance systems, which may contribute to underreporting of RSV cases.
In the future we could face a continuously increasing burden of RSV, with increasingly pressure on healthcare systems, due to the ageing of the population at global level and overlapping in respiratory viruses season (RSV, influenza, COVID-19), with similar clinical symptoms and manifestations.
According to Center of Disease Control and Prevention (CDC), adults at highest risk for severe RSV infection are (25):
Older adults Adults with chronic heart or lung disease Adults with weakened immune systems
ECDC describes as high-risk groups the adults aged 65 years old and above and individuals with specific comorbidities (26). Among the comorbid conditions that are significantly associated with worse outcomes (hospital admission or readmission, emergency department (ED) visits, ICU admission, mortality, etc.) are cardiopulmonary conditions (including COPD and CHF) and immunocompromising conditions (12, 23,27–30).
Adults living in long-term care facilities (LTCFs), nursing homes, and residential living facilities are at greater risk for influenza and RSV infections compared with their counterparts residing in the community in part due to their decreased functional capacity as well as the institutional nature of LTCFs, where exposure to coresidents, visitors, volunteers, and staff is more common (31–33).
Due to the fact that RSV is an important pathogen in older adults, with significant burden of disease, the implementation of preventive measures, confirmed diagnosis, reporting/ surveilling systems and clinical RSV guidelines are a priority. According to ECDC, RSV is not a mandatory reportable disease in European Union (EU), but some countries are performing surveillance of RSV as part of surveillance initiatives for influenza virus and SARS-CoV2. There is large variation regarding the cases definitions that are utilized, types of collected data, the laboratory tests used and the objectives of the surveillance systems.
Due to increasing circulation of respiratory viruses, in December 2022, ECDC made the following recommendations for public health authorities in the EU (26):
Regarding surveillance of RSV, ECDC recommends the inclusion of RSV in the sentinel surveillance systems for acute respiratory infections (ARI) and severe acute respiratory infections, in order to collect sufficient data to monitor the intensity of circulation and spread of respiratory viruses. Upper respiratory specimens from patients with respiratory symptoms should be tested, when possible, using multiplex PCR assays to detect relevant respiratory viruses. Another aspect that should be taken into consideration is implementation of genomic surveillance, RSV typing (A and B), and partial (F and G proteins) or whole genome sequencing.
Until recently, due to the absence of an existing RSV vaccine, preventive measures depended on implementing standard infection control practices that aim to stop the transmission of the virus. These practices include regular handwashing, covering coughs or sneezes with a tissue or one’s arm, using face masks when exhibiting symptoms of the disease, and appropriately disinfecting objects and surfaces as required.
At present, there are no specific antiviral therapies available for the treatment of RSV (34). In older adults, supportive care for RSV infection involves administering fluids, oxygen, and antipyretics to alleviate symptoms. Antivirals, such as ribavirin are sometimes used with the management of severe illness; however, its effectiveness has not been established (35).
Vaccination may provide the best option for prevention of RSV in older adults and adults at high risk. Recently, during the first months of 2023, 2 RSV vaccines for older adults were licensed (36,37).
Since older adults are at a higher risk for more severe outcomes of RSV infection that may result in hampering public health services, the introduction of RSV vaccines, which had proven to be safe and effective, will help substantially reduce this burden by preventing hospitalization and related morbidity after an RSV infection, which could also impact quality of life in this vulnerable population. Furthermore, by reducing public health load, healthcare resources could continue to support all patients during critical respiratory virus season.
There are some licensed vaccines in this moment for people over 60 years and above like:
It is indicated for active immunisation of individuals 60 years of age and older for the prevention of acute respiratory disease and lower respiratory tract disease caused by RSV. A single dose of 0.5 mL should be administered. It is recommended an intramuscular injection into the deltoid region of the upper arm and RSVpreF can be administered concomitantly with seasonal influenza vaccine (QIV, surface antigen, inactivated, adjuvanted).
The mechanism of action started from the two recombinant stabilised RSV prefusion F antigens representing subgroups RSV A and RSV B. Prefusion F is the primary target of neutralizing antibodies that block RSV infection. Following intramuscular administration, the prefusion F antigens elicit an immune response, which protects against RSV-associated lower respiratory tract disease. Efficacy and safety of RSVpreF vaccine in adults were evaluated in 2.
It is indicated for active immunization for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus in adults 60 years of age and older.Administered as a single dose, for intramuscular injection only, preferably in the deltoid muscle RSVpreF3 can be administered also concomitantly with seasonal influenza vaccine (quadrivalent, standard dose, unadjuvanted, inactivated). By combining the RSV-specific antigen, F-protein in prefusion conformation, with an adjuvant system (AS01E), RSVpreF3 is designed to enhance antigen-specific cellular immune response and neutralizing antibodies response in individuals with pre-existing immunity against RSV. The adjuvant AS01E facilitates the recruitment and activation of antigen presenting cells carrying vaccine-derived antigens in the draining lymph node, which in turn leads to the generation of RSVPreF3-specific CD4+ T cells. Efficacy against RSV-associated LRTD in adults 60 years and older was evaluated in an ongoing, Phase III, randomised, placebo-controlled, observer-blind clinical study. The primary population for efficacy analysis included 24 960 participants randomised equally to receive 1 dose of RSVpreF3 vaccine and placebo. At the time of the primary efficacy analysis, participants had been followed for the development of RSV associated LRTD for a median of 6.7 months. The primary objective was to demonstrate the efficacy in the prevention of a first episode of confirmed RSV-A and/or B associated LRTD during the first season. Efficacy in preventing first RSV-associated LRTD with an onset from 15 days after vaccination compared to placebo was 82.6% (96.95% confidence interval of 57.9% to 94.1%) in participants 60 years of age and older. Vaccine efficacy against RSV-LRTD was observed through the median follow-up period of 6.7 months. The vaccine efficacy against RSV A-associated LRTD cases and RSV B-associated LRTD cases was 84.6% (95% CI [32.1, 98.3]) and 80.9% (95% CI [49.4, 94.3]), respectively.
3.
Health organizations around the globe acknowledge the limitations in providing preventive care for RSV infection and have recommended including primary or secondary preventive measures for RSV in their guideline publications (42–45).
Recently, in June 2023, the Joint Committee on Vaccination and Immunisation (JCVI) released an independent report (46) with advice on RSV immunization programme in United Kingdom. Regarding the programme for older adults, the committee noted that an “
As one of the leading causes of respiratory illness in older adults and adults at higher risk, RSV infection can cause serious respiratory illnesses and complications that substantially affect patient morbidity, mortality, and health-related quality of life. Additionally, RSV exerts a significant economic burden on healthcare systems and is often underestimated due to limitations in diagnosis. RSV vaccines represent an opportunity to protect older adults from severe RSV illness.