Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. It is a notable pathogen in all age groups. Infection rates are typically higher during the cold winter months. Infections can cause bronchiolitis in infants, common colds in adults, and more serious respiratory illnesses, such as pneumonia, in older individuals and those with immunocompromise resulting from, e.g., cardiopulmonary disease.
RSV can cause outbreaks in both community and hospital settings. Following initial infection via the eyes or nasal passages, the virus infects the epithelial cells of the upper and lower airways, causing inflammation, cell damage, and airway obstruction. along with the production of fine and ultrafine aerosols during normal breathing, talking, and coughing, and the emerging scientific consensus around transmission of all respiratory infections,
History
RSV was discovered in 1956 when researchers isolated a virus from a population of chimpanzees with respiratory illness. They named the virus chimpanzee coryza agent (CCA). In 1957, this same virus was identified by Robert M. Chanock in children with respiratory illness. Studies of human antibodies in infants and children revealed that the infection was common in early life.
The virus was later renamed human orthopneumovirus, or human respiratory syncytial virus (hRSV).
Several other pneumoviruses show great similarity to hRSV. Bovine RSV (bRSV) shares approximately 80% of its genome with hRSV. It also shares hRSV's predilection for the young, causing more severe disease in calves less than six months old. Because bRSV-infected calves have almost identical symptoms to hRSV-infected children, they have proven to be an important animal model in RSV research. While RSV can cause respiratory tract infections in people of all ages and is among common childhood infections, its presentation often varies between age groups and immune status. Childhood RSV infections are fairly self-limited with typical upper respiratory tract signs and symptoms, such as nasal congestion, runny nose, cough, and low-grade fever. Approximately 15–50% of children will go on to develop more serious lower respiratory tracts infections, such as bronchiolitis, viral pneumonia, or croup. Infants are at the highest risk of disease progression. While several viruses can cause bronchiolitis, RSV is responsible for about 70% of cases.
Adults
Reinfection with RSV remains common throughout life. Reinfection in adulthood often produces only mild to moderate symptoms indistinguishable from the common cold or sinus infection. Symptom severity seems closely related to the extent of immune suppression. Those who have undergone hematopoietic stem cell transplant (HSCT), intensive chemotherapy, and lung transplant are particularly susceptible. Bone marrow transplant patients appear to be at the highest risk, especially before marrow engraftment. In this group, RSV infection carries a nearly 80% risk of both pneumonia and death.
Elderly
RSV or respiratory syncytial virus affects many populations differently. The most at-risk populations for RSV complications are older adults and those with underlying medical conditions or immunocompromised individuals. Between 60,000-160,000 older adults in the United States are hospitalized annually with RSV. Between 6,000 and 10,000 older adults die from RSV infection each year. Additionally RSV can "... lead to worsening of serious conditions such as, Asthma, Chronic obstructive pulmonary disease (COPD) – a chronic disease of the lungs that makes it hard to breathe, and even Congestive heart failure – when the heart can't pump enough blood and oxygen through the body."
- Allergy
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|Adults
|The following are more common in elderly adults or those with underlying immunocompromise or cardiopulmonary conditions:
- Pneumonia
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- Prematurity
- Low birth weight
- Male sex
- Having older siblings
- Maternal smoking during pregnancy
- History of atopy (tendency to develop allergic diseases)
- No breastfeeding
- Household crowding
- Congenital heart or lung disease
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|Adults and elderly
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- Lymphopenia
- Neutropenia
- Graft-versus-host disease
- Use of corticosteroids or myeloablative conditioning regimens
- Recent hematopoietic stem cell transplant
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Virology
thumb|A phylogenetic tree of the pneumovirus and paramyxovirus families
Taxonomy
RSV is a negative-sense, single-stranded RNA virus. It belongs to the genus Orthopneumovirus, family Pneumoviridae, order Mononegavirales.
thumb|Electron micrograph of RSV particle, which has variable shapes
Structure and proteins
thumb|alt=Electron micrograph of RSV|[[Transmission electron microscopy|Electron micrograph of RSV]]
RSV is a medium-sized (~150 nm) enveloped virus. While many particles are spherical, filamentous species have also been identified. There are 11 proteins, described further in the table below.
{| class="wikitable"
|+RSV proteins and their function and location in the virion This protein is highly variable between strains. RSV can spread when an infected person coughs or sneezes, releasing contaminated droplets into the air. Transmission usually occurs when these droplets come into contact with another person's eyes, nose, or mouth. As with all respiratory pathogens once presumed to transmit via respiratory droplets, it is highly likely to be carried by the aerosols generated during routine breathing, talking, and even singing. RSV can also live for up to 25 minutes on contaminated skin (i.e. hands) and several hours on other surfaces like countertops and doorknobs. An estimated of "36% of individuals" can be reinfected with RSV "at least once, during the winter season." The mild symptoms tend to be restricting upper airways. However, younger individuals are extremely vulnerable to developing "severe symptoms," which typically involve the lower airways. confirmation of RSV infection may be warranted in high-risk groups if the result will guide clinical decisions. Common identification techniques include antigen testing, molecular testing, and viral culture.
- Direct fluorescence assay (DFA) allows for direct microscopic examination of virus-infected cells. The sensitivity of DFA testing depends on an adequate specimen. However, they tend to be more expensive and require more complex equipment than other testing methods, making them less practical in resource-limited areas. Molecular testing for RSV is not routinely recommended for all people with respiratory symptoms. However, it may be recommended for those at high risk of RSV complications, such as infants, older adults, and people with chronic medical conditions. RT-PCR has a sensitivity of 90-95% and a specificity of 98-99%, while LAMP has a sensitivity of 95-100% and a specificity of 99-100%.
- Polymerase chain reaction (PCR) is a type of NAAT that allows a very small sample of genetic material to be rapidly amplified into millions of copies for study. PCR is more sensitive than either antigen testing or viral culture.
Differential diagnosis
The differential diagnosis for individuals presenting with signs and symptoms of upper and lower respiratory tract infection includes other viral infections (such as rhinovirus, metapneumovirus, and influenza) and primary bacterial pneumonia. In children, inhaled foreign bodies and congenital conditions such as cystic fibrosis or asthma are typically considered. Mresvia is an mRNA vaccine that was approved for medical use in the United States in May 2024.
The primary pharmaceutical developers, GSK and Pfizer, obtained Food and Drug Administration (FDA) approval for RSV vaccines targeting adults aged 60 and above. GSK's Arexvy boasts 94% efficacy against severe and 83% against symptomatic RSV in this age group, while Pfizer's Abrysvo is 86% effective against severe symptoms and 67% against symptomatic disease in adults aged 60 and older.
Background
thumb|upright=1.15 |F-specific antibodies can be given directly to young children as monoclonal antibodies (mAbs) or acquired through transplacental transfer from mother to child after maternal immunization to protect them. Adenoviruses expressing F or live-attenuated viruses will be used to vaccinate older infants and young children against RSV disease. The RSV fusion protein (F) plays a crucial role in facilitating virus entry by mediating the fusion of viral and host cell membranes. This process involves the transformation of F from a less stable prefusion conformation to a more energetically favorable postfusion state. Antibodies directed against the F protein have demonstrated the ability to hinder viral entry and mitigate RSV-induced diseases. There has been a growing identification of antibodies specifically targeting the prefusion conformation of F. These antibodies exhibit heightened RSV-neutralizing efficacy compared to those binding to F in its postfusion state.
The virus's disease burden and the lack of disease-specific therapies spurs interest and research in vaccine development, which faced obstacles that blocked its progress. Among these were infant-specific factors, such as the immature infant immune system and the presence of maternal antibodies, which make infantile immunization difficult.
RSV-IVIG has since been replaced with the use of a monoclonal antibody (MAb) that can be delivered through muscular injection. Palivizumab (Synagis) is a monoclonal antibody directed against the surface fusion (F) protein of the RSV virus. It was licensed in 1998 and is effective in providing temporary prophylaxis against both RSV A and B. It is given by monthly injections, which begin just before the RSV season and are usually continued for five months. Palivizumab has been shown to reduce both hospitalization rates and all-cause mortality in certain groups of high-risk children (such as those with chronic lung disease, congenital heart disease, and those born preterm). However, its cost limits its use in many parts of the world. More potent derivatives of this antibody have since been developed (including motavizumab) but were associated with considerable adverse events.
The American Academy of Pediatrics (AAP 2014) recommends RSV prophylaxis with palivizumab during RSV season for: Nirsevimab requires only one dose that lasts the entire RSV season, unlike palivizumab, which has to be injected about once a month for up to four times to remain effective. and the United Kingdom in November 2022, and in Canada in April 2023.
Treatment
Supportive care
Treatment for RSV infection is focused primarily on supportive care. This may include monitoring a patient's breathing or using suction to remove secretions from the upper airway. Supplemental oxygen may also be delivered through a nasal cannula or face mask in order to improve airflow. In severe cases of respiratory failure, intubation and mechanical ventilation may be required to support breathing. If signs of dehydration are present, fluids may also be given orally or through an IV.
- Heliox, a mixture of oxygen with helium, may reduce respiratory distress within the first hour of treatment. It works by decreasing airway resistance and easing the work of breathing. However, it has not been shown to affect overall illness outcomes.
- Chest physiotherapy including forced respiratory techniques for infants has not been found to reduce disease severity or yield any other improvement. Evidence supporting other physiotherapy approaches including instrumental physiotherapy and rhinopharyngeal retrograde technique (RRT) is very limited, The effects and any potential use needs further assessment in clinical trials. As such, treatment guidelines do not make recommendations for its use in children. In adults, ribavirin is used off-label and is generally reserved for the severely immunocompromised, such as those undergoing hematopoietic stem cell transplants.
- Immunoglobins, both RSV-specific and non-specific, have historically been used for RSV-related illnesses. However, there is insufficient evidence to support the use of immunoglobins in children with RSV infection.
Anti-inflammatories
- Corticosteroids (systemic or inhaled) have not been found to decrease hospitalization length or disease severity in viral bronchiolitis. Their use may also prolong viral shedding, and thus is not commonly recommended. However, the use of oral corticosteroids remains common in adults with RSV-related exacerbation of underlying lung disease.
Bronchodilators
Bronchodilators, medications commonly used to treat asthma, are sometimes used to treat the wheezing associated with RSV infection. These medications (such as albuterol (sin. salbutamol)) are beta-agonists that relax the muscles of the airways to allow for improved airflow. However, bronchodilators have not been found to improve the clinical severity of infection or the rate of hospitalization among those with RSV infection. Given their limited benefit, plus their adverse event profile, they are not routinely recommended for use in RSV bronchiolitis. Antibiotics target bacterial pathogens, not viral pathogens such as RSV. However, antibiotics may be considered if there is clear evidence that a secondary bacterial infection has developed. Ear infections may also develop in a small number of infants with RSV bronchiolitis, in which case oral antibiotics may sometimes be used. Each year, approximately 30 million acute respiratory illnesses and over 60,000 childhood deaths are caused by RSV worldwide. An estimated 87% of infants will have experienced an RSV infection by the age of 18 months, and nearly all children will have been infected by 3 years. In the United States, RSV is responsible for up to 20% of acute respiratory infection hospitalizations in children under the age of 5. However, the vast majority of RSV-related deaths occur in low-income countries that lack access to basic supportive care. Researchers analyzed over 14,000 SUID cases using CDC records and found that the rate per 100,000 live births increased by 10% between 2019 and 2021. The study revealed that the risk of SUID was highest from June to December 2021, coinciding with an off-season spike in RSV hospitalizations after the virus deviated from its typical winter pattern in 2020.
SARS-CoV-2 infections, the virus responsible for COVID-19, may lead to a higher risk of infection with RSV. In November 2022, the RSV hospitalization rate for newborns was seven times the rate in 2018. This, combined with increasing influenza circulation, caused the US state of Oregon to declare a state of emergency.
The findings of a 2024 cross-sectional study of 6,248 hospitalized adults with RSV infection suggest that acute cardiac events are common among hospitalized older adults with RSV infection, and are associated with severe clinical outcomes. Nearly a quarter of hospitalized people over 50 with RSV experienced an acute cardiac event (most frequently acute heart failure), including 1 in 12 adults (8.5%) without documented underlying cardiovascular disease. Patients who had acute cardiac events had nearly twice the risk of a severe outcome than patients who did not.