RSV Respiratory syncytial virus

The most common cause of lower respiratory tract infection in infants.

RSV is a leading cause of death in infants younger than six months of age, particularly in low and middle income countries.

Most common cause of brochiolitis and pneumonia in children aged <1 year worldwide.

Severe RSV associated lower respiratory tract illness peaks in the first 2 to 3 months of life, despite the presence of naturally acquired maternal antibodies.

Among children younger than five years of age, it is associated with approximately 33 million cases of lower respiratory tract illness, 3.6 million hospital admissions, and more than 100,000 deaths each year.

More than 95% of cases of RSV associated acute lower respiratory tract infection, and RSV attributed deaths occur in low to middle income countries.

Infants younger than six months of age, or at the greatest risk for RSV, associated illness and death, and more than 95% of RSV associated deaths occur in low and middle income countries.

Infants and young children, who were born prematurely, or who have certain underlying medical conditions, have an increased risk of life-threatening RSV disease.

Most infants and young children hospitalized with RSV are previously healthy.

RSV typically spreads during winter epidemics in temperate climates, and during rainy seasons in tropical climate regions.

Most infections result in mild or no disease, but as many as 2 to 3% of infants were hospitalized with RSV during their first year of life, which makes RSV a leading cause of hospitalization in children, younger than five years of age.

Estimated 75,000-125,000 hospitalizations of infants annually in the US.

It is an important cause of illness and death in older adults.

Approximately 60,000 to 160,000 RSV associated hospitalizations, and 6000 to 10,000 RSV associated deaths occur each year in older adults in the US.

In most adults with RSV there a mild cold-like symptoms of cough, runny nose, fever that typically last less than five days.

In  older adults RSV can cause severe illness, such as pneumonia, or can worsen respiratory diseases, including asthma, or COPD.

An important cause of acute respiratory infections during autumn and winter months in temperate regions, and during rainy seasons in tropical areas.

The risk of severe RSV disease is increased in frail older adults and those with coexisting conditions, including congestive heart failure, stroke, chronic kidney disease, COPD and immunosuppression.

It is a major cause of death rivaling seasonal influenza, among frail older adults.

RSV illness develops in 3 to 7% of adults older than 65 years of age, resulting in 177,000 hospitalizations and 14,000 deaths.

RSV illness develops in approximately 3 to 7% of healthy older adults in the United States each year, with an estimated 177,000 hospitalizations, and 14,000 deaths each year in the United States.

18% of older adults are hospitalized with RSV in an ICU setting, 31% receive home health services at discharge and 26% die within one year after admission.

A diagnosis of RSV infections in adults is likely underestimated, because reporting is not required and testing is not routinely routinely performed and may be unreliable.

RSV shedding, occurs at higher levels, and for longer duration in older adults than in younger adults.ad

Approximately one or 2 per 1000 US adults 65 years of age or older are hospitalized with RSV associated pneumonia or exacerbation of underlying cardiopulmonary conditions each year, with a case fatality rate of 1 to 2%.

Causes predictable, annual outbreaks of respiratory

tract disease in temperate as well as tropical climates around the world.

In 2015 an estimated 3.2 million hospitalizations for RSV associated pneumonia occurred in children younger than five years of age worldwide, and 118,000 of the hospitalized children died.

In the above study approximately 44% of those hospitalizations and 46% of the in-hospital deaths occurred in infants younger than six months of age.

Causes substantial morbidity and mortality among infants, older adults, and in immunocompromised adults.

Results in largely predictable annual epidemics worldwide.

It is a leading cause of infant deaths, primarily in low income and middle income countries.

During the first year of life infants with the primary RSV infection are at a risk for severe lower respiratory tract infection.

Preterm infants, as well as young children with chronic lung disease of prematurity or  congenital heart disease or a particularly high risk.

An estimated 177,000 hospitalizations and 14,000 deaths per year in adults 65 years of age or older.

An estimated 57,000 hospitalizations and 500,000 ED visits among children 5 years or younger each year.

80% of RSV visits are outpatient ones.

Globally RSV infections in children younger than five years of age causes an estimated 3.2 million hospitalizations and 95,000 to 150,000 deaths, primarily in the developing world.

Severe disease in childhood associated with progression to asthma.

A leading cause of hospitalization in adults with community-acquired respiratory disease.

Causes 50 to 90 percent of hospitalizations for bronchiolitis, 5 to 40 percent of those for pneumonia, and 10 to 30 percent of those for tracheobronchitis.

A negative single stranded RNA virus that generates double stranded RNA during replication.

RSV is a negative-sense, single-stranded RNA virus of the family Paramyxoviridae.

Family Paramyxoviridae includes common respiratory viruses such as those causing measles and mumps.

Its  RNA genome encodes for 11 viral proteins.

Two major viral groups RSV A and RSV B may cocirculate and are antigenically stable.

Protection is transient, and infections recur.

Three structural proteins populate the viral surface envelope – the attachment of G protein, the fusion, F, proteins, and a small hydrophobic proteins.

F and G proteins play a critical role in the viruses infectivity and pathogenesis.

The G protein binds to receptors on ciliated epithelium cells of the respiratory tract allowing the F proteins to fuse the viral and cellular membranes and enables the viral genome to access the intracellular environment with viral replication occurs.

After infection more than 90% of neutralizing antibodies are directed against the F protein.

The F protein is hidden in the post fusion state presenting challenges to the development of a monoclonal antibody and vaccine.

The RSV fusion (F) F glycoprotein is anchored in the viral envelope in a metastable state, and undergoes structural rearrangement to a stable post fusion state is it fuses the viral envelope with the cell membrane during viral entry.

Pre-fusion F is the major target of potent virus neutralizing antibodies and the key vaccine antigen.

F family Paramyxoviridaeproteins on the surface of the virus cause the cell membranes on adjacent cells to merge, forming syncytia.

RSV F protein nanoparticle vaccination in pregnant women did not need pre-specified success criteria for efficacy against RSV associated pneumonia in infants up to 90 days of life.

RSV pre-fusion S protein based vaccine (RSVPpreF) contain stabilized pre-fusion F glycoproteins from RSV sub groups A and B in trials is effective against symptomatic RSV infection and viral shedding.

A prophylactic medication exists for preterm birth infants and infants with a congenital heart defect (CHD) or bronchopulmonary dysplasia.

Treatment is limited to supportive care, including oxygen therapy.

Annual epidemic occurs during the winter months.

In tropical climates, infection is most common during the rainy season.

60% of infants are infected during their first RSV season.

The most common cause of hospital admission in the winter season during the first year of life.

RSV bronchiolitis is associated with increased rates of early wheezing, asthma, and possible allergic sensitization later in life.

Early childhood wheezing after such an infection has a high prevalence and can influence the quality of life and can generate substantial health care costs.

Essentially all children will have been infected with the virus by 2–3 years of age.

Of those infected with RSV, 2–3% will develop serious bronchiolitis requiring hospitalization.

Infection with RSV induces protective immunity which wanes with time, so individuals can be infected multiple times, even during a single RSV season.

Severe RSV infections have increasingly been found among elderly.

Capable of causing severe infection complications including bronchiolitis and pneumonia in susceptible patients including the very young, very old and those with chronic conditions such as heart disease or asthma.

25-40% of children under the age of 1, following initial exposure of virus develop symptoms of bronchiolitis or pneumonia.

Re-infection in young adults may be asymptomatic or appear as sinusitis or an URI.

Most infections associated with only mild symptoms, manifesting common colds and minor illnesses.

For some children severe respiratory illness requires hospitalization and, rarely, causes death, which is more likely to occur in premature infants or immunocompromised.

Common symptoms among infants include listlessness, anorexia, and possible fever.

Respiratory symptoms of wheezing and asthma develop more commonly among children who experience severe RSV infection.

PCR testing for RSV nucleic acids in peripheral blood can help establish diagnosis.

Most commonly used types of RSV clinical laboratory tests are;

Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR), which is more sensitive than culture and antigen testing

Antigen testing, which is highly sensitive in children but not sensitive in adults

SH, G and F proteins form the viral coat.

The G protein is a surface protein, heavily glycosylated and functions as the attachment protein.

The F protein mediates fusion, allowing entry of the virus into the cell cytoplasm and is associated with formation of syncytia.

Antibodies directed at the F protein are neutralizing.

RSV spreads easily by direct contact.

Remains viable for a half an hour or more on hands or for up to 5 hours on surfaces.

Palivizumab (Synagis), is a monoclonal antibody directed against RSV surface fusion protein moderately effective prophylactic drug is available for infants at high risk.

Palivizumab is given by monthly injections, just prior to the RSV season and are usually continued for five months in premature infants or in children with cardiopulmonary disease.

Ribavirin has limited efficacy.

Ribavirin is aerosolized and limited to hospitalized infants and young children with severe lower airway disease.

Ribavirin is rarely used due to its toxicity profile teratogenic potential, and questionable efficacy.Infection can be confirmed using Direct Fluorescent Antibody detection (DFA), Chromatographic rapid antigen detection or detection of viral RNA using RT PCR and quantification of viral load can be determined by Plaque Assay, antigen capture enzyme immunoassay (EIA), and ELISA.

Assay of antibody levels can be achieved by HAI and Neutralisation assay.

Nebulized 3% hypertonic saline a safe, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis, and s associated with a 26% reduction in length of stay compared with an untreated group.

Supportive care includes fluids, oxygen, and albuterol.

Corticosteroids confer no benefit.

Pavlivizumab is a monoclonal antibody directed against the F proteins and reduces the risk of hospitalization for RSV among patients with risk factors, but has modest efficacy requiring monthly intramuscular administration, and is associated with the emergence of viral strains with mutations in the proteins.

Pavlivizumab is an RSV specific monoclonal antibody approved only for the prevention of serious lower respiratory tract disease caused by RSV in high risk pediatric patients such as premature infants and those with cardiac with pulmonary conditions.

RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer without safety concerns, suggesting reduction of RSV infections in infants (Simones AF).

RSVpreF vaccine administered during pregnancy is effective against medically, attended severe RSVP associated lower respiratory tract illness in infants, without safety concerns ( Kampmann B).

RSVpreF vaccine prevents RSV associated lower respiratory tract illness and RSV associated acute respiratory illness in adults 60 years of age or greater without safety concerns. (Walsh EE).

Nirsevimab a monoclonal anybody with an extended halflife when given as a single injection,resulted in fewer  medically tended RSV-associated lower respiratory tract infections and hospitalizations than placebo.

Nirsevimab use resulted in RSV associated lower respiratory tract infection at a rate that was 70% lower than with placebo through 150 days after administration, and the incidence of hospitalization for RSV was 78% lower.

A single injection of nirsevimab administed before the RSV season protects healthy late preterm and term events from RSV associated lower respiratory tract infection (MELODY study group).

EDP-938 is a non-fusion replication inhibitor of RSV that modulates the viral nucleoprotein.

EDP-938 is superior to placebo with regard to lowering viral load, total symptom scores, and mucus weight without a parent safety concerns in RSV infection (Ahmad A).

The US Food and Drug Administration (FDA) has approved Arexvy, and Abryso the first respiratory syncytial virus (RSV) vaccines approved for use in the United States: for the prevention of lower respiratory tract disease caused by RSV in individuals 60 years of age and older.

CDC recommending vaccine immunization to protect infants under eight months and some older babies at increased risk of severe illness from respiratory syncytial virus.

A single dose mono clonal antibody, nirsevimab-slip, prevents respiratory syncytial virus disease, in infants and children up to two years: lowers respiratory tract infection by 70 to 75% compared with placebo.

RSV infection can be decreased if people wash their hands, cover their coughs and sneezes, avoid close contact, such as kissing, shaking, hands, and sharing glasses with others.

Disinfecting surfaces and encouraging individuals with respiratory symptoms to remain at home can decrease the risk of RSV transmission.