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. Its name is derived from the large, multinucleated cells known as syncytia that form when infected cells fuse.

RSV is a common cause of respiratory hospitalization in infants, and reinfection remains common in later life, though often with less severity. 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. A variety of methods are available for detecting and diagnosing RSV, including antigen testing, molecular testing, and viral culture.

Other than vaccination, prevention measures include hand-washing and avoiding close contact with infected individuals. The carriage of RSV in respiratory aerosols, 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, may suggest airborne precautions are needed for reliable protection. In May 2023, the US Food and Drug Administration (FDA) approved the first RSV vaccines, Arexvy (developed by GSK plc) and Abrysvo (Pfizer). The prophylactic use of palivizumab or nirsevimab (both are monoclonal antibody treatments) can prevent RSV infection among infants with high-risk predispositions.

Treatment for severe illness is primarily supportive, including oxygen therapy and more advanced breathing support with continuous positive airway pressure (CPAP) or nasal high flow oxygen, as required. In cases of severe respiratory failure, intubation and mechanical ventilation may be required. Ribavirin is an antiviral medication licensed for the treatment of RSV infection in children.

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. Since bRSV-infected calves' symptoms are almost identical to those of hRSV-infected children, they have proven to be an important animal model for RSV research.

Signs and symptoms RSV infection can present with a wide variety of signs and symptoms ranging from mild upper respiratory tract infections (URTI) to severe and potentially life-threatening lower respiratory tract infections (LRTI) necessitating hospitalization and mechanical ventilation. 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. Reinfection is common throughout life, but infants and the elderly remain at risk for symptomatic infection.

Children Nearly all children in the United States experience at least one RSV infection before two years of age. 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. Inflammation of the nasal mucosa (rhinitis) and throat (pharyngitis), as well as redness of the eyes (conjunctival infection), may be seen on exam. 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.

Bronchiolitis is a common lower respiratory tract infection characterized by inflammation and obstruction of the small airways in the lungs. While several viruses can cause bronchiolitis, RSV is responsible for about 70% of cases. It usually presents with 2 to 4 days of runny nose and congestion followed by worsening cough, noisy breathing, tachypnea (fast breathing), and wheezing. As infants work harder to breathe, they can also show signs of respiratory distress, such as subcostal retractions (when the belly pulls under the ribcage), intercostal retractions (when the muscles between the ribs pull inward), grunting, and nasal flaring. If the child has not been able to feed adequately, signs of dehydration may also be present. Fever may be present, but high-grade fever is uncommon. Crackles and wheezing can often be heard on auscultation, and oxygen saturation levels may be decreased.

In very young infants under six weeks of age, especially premature infants, signs of infection may be less specific. They may have minimal respiratory involvement. Instead, they may exhibit decreased activity, irritability, poor feeding, or breathing difficulties. This can also be accompanied by apneic spells, or brief pauses in breathing.

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. Infection may also be asymptomatic. If present, symptoms are generally isolated to the upper respiratory tract: runny nose, sore throat, fever, and malaise. In most cases, nasal congestion precedes the development of cough. Unlike other upper respiratory infections, RSV is more likely to cause new-onset wheeze in adults. About 25% of infected adults will progress to significant lower respiratory tract infections, such as bronchitis or tracheobronchitis.

While RSV very rarely causes severe disease in healthy adults, it can cause morbidity and mortality in the elderly and in those with underlying immune compromise or cardiopulmonary disease. Older adults present similarly to younger adults but tend to have greater symptom severity with an increased risk of lower respiratory tract involvement. In particular, the elderly are more likely to experience pneumonia, respiratory distress, and death.

Immunocompromised In both adults and children, those who are immunocompromised are at an increased risk of severe infection with RSV. Infected individuals in this group are more likely to progress from upper to lower respiratory tract involvement and have prolonged viral shedding. 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 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."

Expedient and proper medical care is important for older adults, as waiting or receiving a misdiagnosis can be associated with an increased risk of complications. As of August 2023, adults aged 60 years and older qualify for vaccination against RSV in Canada and the United States.

Complications PopulationComplications of RSV infectionChildren Short-term, hospitalized children are at risk of developing: Atelectasis / pulmonary infiltrates Acute otitis media Lung hyperinflation Respiratory failure Apnea Bacterial pneumonia

Long-term, children are at risk of developing the following chronic conditions that may persist into adulthood: Asthma and recurrent wheezing, particularly among those with severe RSV infection in early life Allergy Acute neurologic complicationsAdultsThe following are more common in elderly adults or those who are immunocompromised or have cardiopulmonary conditions: Pneumonia Respiratory distress Acute exacerbation of underlying chronic illness (COPD, asthma, congestive heart failure) Permanent decline in lung function in patients with COPDImmunocompromisedSome immunocompromised groups are at higher risk of specific complications, such as: Bone marrow transplant recipients → pneumonia, death Lung transplant recipients → chronic graft dysfunction, acute pneumonitis, obliterative bronchiolitis

Risk factors Risk factors for the development of severe lower respiratory tract infection with RSV vary by population. PopulationRisk factors for progression to lower respiratory infection with RSVChildren 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 diseaseAdults and elderly Older age (>65 years of age) Chronic heart or lung disease (especially COPD) Functional disability Residence in a care homeImmunocompromised Lymphopenia Neutropenia Graft-versus-host disease Use of corticosteroids or myeloablative conditioning regimens Recent hematopoietic stem cell transplant

Virology

Taxonomy RSV is a negative-sense, single-stranded RNA virus. The scientific name for this viral species is human orthopneumovirus. This is synonymous with human respiratory syncytial virus (hRSV), which is often shortened to just RSV. It belongs to the genus Orthopneumovirus, family Pneumoviridae, order Mononegavirales. Its name comes from the fact that F proteins on the surface of the virus cause neighboring cell membranes to merge, creating large multinucleated syncytia.

Antigenic subtypes RSV is divided into two antigenic subtypes, A and B, based on the reactivity of the F and G surface proteins to monoclonal antibodies. The subtypes tend to circulate simultaneously during local epidemics, although subtype A is usually more prevalent. Generally, RSV subtype A (RSVA) is thought to be more virulent than RSV subtype B (RSVB), with higher viral loads and faster transmission time. To date, 16 RSVA and 22 RSVB clades have been identified. Among RSVA, the GA1, GA2, GA5, and GA7 clades predominate; GA7 is found only in the United States. Among RSVB, the BA clade predominates worldwide.

Genome

RSV has a negative-sense, single-stranded RNA genome. The genome is linear and approximately 15,000 nucleotides in length. It has 10 genes encoding for 11 proteins. The gene order is NS1-NS2-N-P-M-SH-G-F-M2-L, with the NS1 and NS2 gene serving as nonstructural promoter genes.

Structure and proteins