RSV

RSV short for respiratory syncytial virus, is a common respiratory virus that usually causes mild, cold-like symptoms. Most people recover in a week or two, but RSV can be serious, especially for infants and older adults. In fact, RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia (infection of the lungs) in children younger than 1 year of age in the United States. RSV is also a significant cause of respiratory illness in older adults.

Respiratory syncytial virus (RSV) was discovered in 1956 and has since been recognized as one of the most common causes of childhood illness ¹⁾. RSV causes annual outbreaks of respiratory illnesses in all age groups. In most regions of the United States, RSV usually circulates during fall, winter, and spring, but the timing and severity of RSV season in a given community can vary from year to year. Healthcare professionals should consider RSV in patients with severe respiratory illness, particularly during the RSV season.

Almost all children will have had an RSV infection by their second birthday. People infected with RSV usually show symptoms within 4 to 6 days after getting infected.

There is no specific treatment for RSV infection, though researchers are working to develop vaccines and antivirals (medicines that fight viruses).

Most RSV infections go away on their own in a week or two. You can manage fever and pain with over-the-counter fever reducers and pain relievers, such as acetaminophen or ibuprofen. Talk to your healthcare provider before giving your child nonprescription cold medicines, since some medicines contain ingredients that are not recommended for children. It is important for people with RSV infection to drink enough fluids to prevent dehydration (loss of body fluids).

Healthy infants and adults infected with RSV do not usually need to be hospitalized. But some people with RSV infection, especially infants younger than 6 months of age and older adults, may need to be hospitalized if they are having trouble breathing or are dehydrated. In most of these cases, hospitalization only lasts a few days.

Visits to a healthcare provider for an RSV infection are very common. During such visits, the healthcare provider will evaluate how severe the person’s RSV infection is to determine if the patient should be hospitalized. In the most severe cases, a person may require additional oxygen or intubation (have a breathing tube inserted through the mouth and down to the airway) with mechanical ventilation (a machine to help a person breathe).

RSV is a widespread pathogen of humans, due in part to the lack of long-term immunity after infection, making reinfection frequent. It infects 90% of children within the first 2 years of life and frequently reinfects older children and adults. The majority of patients with RSV will have an upper respiratory illness, but a significant minority will develop lower respiratory tract illness, predominantly in the form of bronchiolitis. Children under the age of one year are especially likely to develop lower respiratory involvement, with up to 40% of primary infections resulting in bronchiolitis. Worldwide, it is estimated that RSV is responsible for approximately 33 million lower respiratory tract illnesses, three million hospitalizations, and up to 199,000 childhood deaths; the majority of deaths are in resource-limited countries. There is seasonal variation in RSV incidence, but seasonal effects vary with worldwide geography; temperate climates have a marked winter-spring predominance, and tropical and equatorial climates may have less pronounced spikes with the more interseasonal disease. Morbidity and mortality are significantly higher in a subset of patients, including premature infants, patients with preexisting cardiac, pulmonary, neurologic, and immunosuppressive disorders, and the elderly ²⁾.

Figure 1. Respiratory syncytial virus (RSV)

Footnote: The structure of respiratory syncytial virus (RSV). The RSV genome is 15.2 kb of nonsegmented negative-sense RNA encoding 11 viral proteins. Viral envelope of RSV contains three transmembrane glycoproteins: attachment glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH). Matrix proteins (M) are present on the inner side of the viral envelope. Viral RNA is tightly encapsidated by nucleoproteins (N) and the large proteins (L), phosphoproteins (P), and M2-1 proteins that mediate viral RNA transcription. M2-2 protein regulates viral RNA synthesis.

[Source ³⁾ ]

Is there vaccine for RSV?

There is no vaccine yet to prevent RSV infection, but scientists are working hard to develop one. While most acute respiratory viral infections, such as influenza (flu), elicit long-term durable immune responses, RSV infection only leads to relatively short-lived protective immunity, which is why frequent RSV reinfection can occur throughout a patient’s life ⁴⁾. Several attempts have been made to develop an effective RSV vaccine. However, no vaccine exists today because candidates failed to induce persistent immune responses against RSV antigen without causing vaccine-associated disease enhancement ⁵⁾.

However, there is a medicine that can help protect some babies at high risk for severe RSV disease. Healthcare providers usually give this medicine called palivizumab to premature infants and young children with certain heart and lung conditions as a series of monthly shots during RSV season. If you are concerned about your child’s risk for severe RSV infection, talk to your child’s doctor.

What is RSV?

RSV or respiratory syncytial virus, an enveloped, single-stranded, negative-strand, RNA virus belonging to the Paramyxoviridae family, and is in the genus Pneumovirus ⁶⁾. RSV was discovered in chimpanzees in 1956 and subsequently confirmed to be a human pathogen shortly after that. There are several animal respiratory syncytial viruses in the same genus as human RSV, which do not infect humans. The structure of RSV is that of a bilipid-layer-envelope surrounding a ribonucleoprotein core, with several membrane proteins, one of which functions in attachment to host cells, and one of which functions in fusion to host cells. There is only one serotype of RSV, but it is classified into two strains, “A” and “B,” with differences consisting of variation in the structure of several structural membrane proteins, most especially the attachment protein ⁷⁾.

RSV is classified into subgroups A and B based on reactivity against monoclonal antibodies, with most differences occurring in the G protein ⁸⁾. A study demonstrated that subtype A is more virulent than subtype B ⁹⁾. The 15.2 kb RSV genome is a non-segmented negative-sense RNA encoding 11 viral proteins, namely nonstructural proteins NS1 and NS2, nucleoprotein (N), phosphoprotein (P), matrix protein (M), small hydrophobic protein (SH), attachment glycoprotein (G), fusion protein (F), M2-1, M2-2, and large protein (L) ¹⁰⁾. The RSV envelope contains three surface transmembrane glycoproteins, specifically G, F, and SH (see Figure 1). Airway epithelial cells have been considered a primary target of RSV, with binding and entry of RSV into host cells mediated by the G and F proteins ¹¹⁾. The G protein, which is expressed as soluble (Gs) and membrane-bound (Gm) forms, is responsible for viral attachment to host cells and immune modulation by RSV ¹²⁾. RSV entry is mediated by the F protein, which undergoes a conformational change and fuses the viral envelope with the host cell membrane ¹³⁾. Several candidate molecules have been proposed as an RSV receptor, including CX3 chemokine receptor 1 (CX3CR1) ¹⁴⁾, DC-SIGN ¹⁵⁾, heparan sulfate proteoglycans (HGPGs) ¹⁶⁾, and annexin II ¹⁷⁾. The G protein contains a CX3C motif that can bind the CX3CR1 receptor on host cells; mutation of this motif or inhibition of the G-CX3CR1 interaction with a blocking anti-CX3CR1 antibody is reported to reduce RSV infection ¹⁸⁾. Recently, nucleolin was identified as a functional fusion receptor for RSV ¹⁹⁾. Silencing lung nucleolin using specific siRNA resulted in diminished RSV titers in infected mice, suggesting nucleolin as a functional cellular receptor for RSV ²⁰⁾. The SH protein forms a pentameric ion channel that enhances membrane permeability in the host ²¹⁾. Studies demonstrated that deletion of SH in RSV leads to viral attenuation ²²⁾. Although all three RSV surface proteins (F, G, and SH) are major targets of humoral immune responses, vaccine development for RSV has been focused primarily on the F protein, which is generally conserved across all known RSV strains ²³⁾. Published reports have shown that F protein-specific antibodies induce the most neutralizing activity, suggesting a critical role for this protein ²⁴⁾. M proteins, which are present on the interior side of the viral envelope, consist of a structural component and play an essential role in viral assembly and filament formation ²⁵⁾. Viral RNA is tightly encapsidated by N proteins and the L, P, and M2-1 proteins that carry out viral RNA transcription ²⁶⁾. The RSV M2-2 protein is involved in maintaining the balance between viral genome replication and transcription by negatively regulating viral transcription ²⁷⁾. Although the non-structural proteins NS1 and NS2 do not directly participate in RNA replication, NS proteins facilitate RSV replication by disrupting type I IFN signaling in the host ²⁸⁾.

The Th1 and cytotoxic CD8+ T cell responses are both crucial for viral clearance and pathogenesis following RSV infection ²⁹⁾. Moreover, RSV-specific neutralizing antibody responses confer protection against RSV infection ³⁰⁾. It was reported that RSV-specific serum-neutralizing antibody levels were positively related to the resistance against RSV infection in adults ³¹⁾ and the elderly ³²⁾, and the severity of RSV reinfection was inversely related to the titers of serum-neutralizing antibodies in children ³³⁾. Further, passive transfer with Palivizumab, a humanized murine monoclonal neutralizing antibody to RSV F protein, achieved protection against infection with RSV in young children ³⁴⁾ indicating a protective role of antibodies during RSV infection. Interestingly, RSV-specific nasal IgA seems to be more effective than serum IgA to prevent RSV infection, but IgA+ memory B cells were undetectable at convalescence ³⁵⁾. As nasal IgA is responsible for protection against RSV, inducing durable nasal IgA responses is considered an effective approach for RSV vaccine development. In addition, recent studies showed that passive administration of antibodies to RSV G protein also efficiently prevents RSV infection in mice, while treatment with the neutralizing antibody Palivizumab, which targets the F protein of RSV, is the only FDA-approved method for prevention of RSV infection ³⁶⁾. Animal models ³⁷⁾ and human studies ³⁸⁾ of RSV infection demonstrated that Th2 cytokines (e.g., interleukin (IL)-4, IL-5, and IL-13) contribute to airway pathogenesis following RSV infection, suggesting that inappropriate activation of Th2 responses is harmful for RSV-infected hosts. Although there were several attempts to develop a safe and effective RSV vaccine, the potential candidates repeatedly failed to confer effective protection. Furthermore, some vaccine candidates caused enhanced respiratory disease, rather than protection, upon exposure to RSV. Studies conducted in 1966–1967 demonstrated that administration of formalin-inactivated RSV vaccines (FI-RSV) to infants and children resulted in severe respiratory disease upon subsequent natural RSV infection ³⁹⁾. Hospitalization was required for 80% of the participants, and two vaccinated infants died upon infection, implying that primary immunization with FI-RSV induced aberrant pathologic responses. Indeed, subsequent studies on animal models revealed that FI-RSV boosted Th2-mediated immune responses ⁴⁰⁾.

Although an imbalance between Th1/Th2 immune responses accounts for the immunopathology during RSV infection, regulatory T cells (Tregs) are also essential for regulating a robust inflammatory response. Treg depletion leads to enhanced RSV disease accompanied by severe weight loss and delayed recovery ⁴¹⁾. Selective chemoattraction of Tregs to the airway by chemokine CCL17/22 administration ameliorated RSV vaccine-induced lung disease ⁴²⁾. Consistent with these findings, injection of an IL-2/anti-IL-2 immune complex resulted in Treg accumulation and reduced lung inflammation following RSV infection ⁴³⁾, indicating that Tregs are responsible for controlling disease severity during RSV infection.

RSV Transmission

RSV can spread when an infected person coughs or sneezes. You can get infected if you get droplets from the cough or sneeze in your eyes, nose, or mouth, or if you touch a surface that has the virus on it, like a doorknob, and then touch your face before washing your hands. Additionally, it can spread through direct contact with the virus, like kissing the face of a child with RSV.

People infected with RSV are usually contagious for 3 to 8 days. However, some infants, and people with weakened immune systems, can continue to spread the virus even after they stop showing symptoms, for as long as 4 weeks. Children are often exposed to and infected with RSV outside the home, such as in school or child-care centers. They can then transmit the virus to other members of the family.

RSV can survive for many hours on hard surfaces such as tables and crib rails. It typically lives on soft surfaces such as tissues and hands for shorter amounts of time.

People of any age can get another RSV infection, but infections later in life are generally less severe. People at highest risk for severe disease include:

• premature infants
• young children with congenital (from birth) heart or chronic lung disease
• young children with compromised (weakened) immune systems due to a medical condition or medical treatment
• adults with compromised immune systems
• older adults, especially those with underlying heart or lung disease

In the United States and other areas with similar climates, RSV infections generally occur during fall, winter, and spring. The timing and severity of RSV circulation in a given community can vary from year to year.

RSV pathophysiology

RSV is spread from person to person via respiratory droplet, and the incubation period after inoculation with RSV ranges from 2 to 8 days, with a mean incubation of 4 to 6 days, depending on host factors such as the age of the patient and whether it is the patient’s primary infection with RSV. After inoculation into the nasopharyngeal or conjunctival mucosa, the virus rapidly spreads into the respiratory tract, where it targets its preferred growth medium: apical ciliated epithelial cells. There it binds to cellular receptors using the RSV-G glycoprotein, then uses the RSV-F fusion glycoprotein to fuse with host cell membranes and insert its nucleocapsid into the host cell to begin its intracellular replication. Host inflammatory immune response is triggered, including both humoral and cytotoxic T-cell activation, and a combination of viral cytotoxicity and the host’s cytotoxic response cause necrosis of respiratory epithelial cells, leading to downstream consequences of small airway obstruction and plugging by mucus, cellular debris, and DNA. More severe cases may also include alveolar obstruction. Other downstream effects include ciliary dysfunction with impaired mucus clearance, airway edema, and decreased lung compliance ⁴⁴⁾.

People at high risk for severe RSV infection

Most people who get an RSV infection will have mild illness and will recover in a week or two. Some people, however, are more likely to develop severe RSV infection and may need to be hospitalized. Examples of severe infections include bronchiolitis (an inflammation of the small airways in the lung) and pneumonia. RSV can also make chronic health problems worse. For example, people with asthma may experience asthma attacks as a result of RSV infection, and people with congestive heart failure may experience more severe symptoms triggered by RSV. The following groups of people are more likely to get serious complications if they get sick with RSV:

RSV in Infants and Young Children

RSV can be dangerous for some infants and young children. RSV infection can cause a variety of respiratory illnesses in infants and young children. It most commonly causes a cold-like illness but can also cause lower respiratory infections like bronchiolitis and pneumonia. One to two percent of children younger than 6 months of age with RSV infection may need to be hospitalized. Each year in the United States, an estimated 57,000 children younger than 5 years old are hospitalized due to RSV infection. Severe disease most commonly occurs in very young infants.

Infants and Young Children at greatest risk for severe illness from RSV include:

• Premature infants
• Very young infants, especially those 6 months and younger
• Children younger than 2 years old with chronic lung disease
• Children younger than 2 years old with chronic heart disease
• Children with weakened immune systems
• Children who have neuromuscular disorders, including those who have difficulty swallowing or clearing mucus secretions.

Infants and young children with RSV infection may have rhinorrhea and a decrease in appetite before any other symptoms appear. Cough usually develops one to three days later. Soon after the cough develops, sneezing, fever, and wheezing may occur. In very young infants, irritability, decreased activity, and apnea may be the only symptoms of infection.

Most otherwise healthy infants and young children who are infected with RSV do not need hospitalization. Those who are hospitalized may require oxygen, intubation, and/or mechanical ventilation. Most improve with supportive care and are discharged in a few days.

Severe RSV infection

Virtually all children get an RSV infection by the time they are 2 years old. Most of the time RSV will cause a mild, cold-like illness, but it can also cause severe illness such as:

• Bronchiolitis (inflammation of the small airways in the lung)
• Pneumonia (infection of the lungs)

One to two out of every 100 children younger than 6 months of age with RSV infection may need to be hospitalized. Those who are hospitalized may require oxygen, intubation, and/or mechanical ventilation (help with breathing). Most improve with this type of supportive care and are discharged in a few days.

RSV in older Adults and Adults with Chronic Medical Conditions

RSV infections can be dangerous for certain adults. Each year, it is estimated that more than 177,000 older adults are hospitalized and 14,000 of them die in the United States due to RSV infection. Adults at highest risk for severe RSV infection include:

• Older adults, especially those 65 years and older
• Adults with chronic heart or lung disease
• Adults with weakened immune systems

Severe RSV infection

When an adult gets RSV infection, they typically have mild cold-like symptoms. But RSV can sometimes lead to serious conditions such as:

• Pneumonia (infection of the lungs)
• More severe symptoms for people with asthma
• More severe symptoms for people with chronic obstructive pulmonary disease (COPD) (a chronic disease of the lungs that makes it hard to breathe)
• Congestive heart failure (when the heart can’t pump blood and oxygen to the body’s tissues)

Older adults who get very sick from RSV may need to be hospitalized. Some may even die. Older adults are at greater risk than young adults for serious complications from RSV because our immune systems weaken when we are older.

RSV Prevention

There are steps you can take to help prevent the spread of RSV. Specifically, if you have cold-like symptoms you should:

• Cover your coughs and sneezes with a tissue or your upper shirt sleeve, not your hands
• Wash your hands often with soap and water for 20 seconds
• Avoid close contact, such as kissing, shaking hands, and sharing cups and eating utensils, with others

In addition, cleaning contaminated surfaces (such as doorknobs) may help stop the spread of RSV.

Ideally, people with cold-like symptoms should not interact with children at high risk for severe RSV disease, including premature infants, children younger than 2 years of age with chronic lung or heart conditions, and children with weakened immune systems. If this is not possible, they should carefully follow the prevention steps mentioned above and wash their hands before interacting with such children. They should also refrain from kissing high-risk children while they have cold-like symptoms.

Parents of children at high risk for developing severe RSV disease should help their child, when possible, do the following:

• Avoid close contact with sick people
• Wash their hands often with soap and water
• Avoid touching their face with unwashed hands
• Limit the time they spend in child-care centers or other potentially contagious settings, especially during fall, winter, and spring. This may help prevent infection and spread of the virus during the RSV season.

Researchers are working to develop RSV vaccines, but none are available yet. A drug called palivizumab is available to prevent severe RSV illness in certain infants and children who are at high risk for severe disease. For example, infants born prematurely or with congenital (from birth) heart disease or chronic lung disease. The drug can help prevent serious RSV disease, but it cannot help cure or treat children already suffering from serious RSV disease, and it cannot prevent infection with RSV. If your child is at high risk for severe RSV disease, talk to your healthcare provider to see if palivizumab can be used as a preventive measure.

RSV Prophylaxis for High-Risk Infants and Young Children

Palivizumab is a monoclonal antibody recommended by the American Academy of Pediatrics ⁴⁵⁾ to be administered to high-risk infants and young children likely to benefit from immunoprophylaxis based on gestational age and certain underlying medical conditions. It is given in monthly intramuscular injections during the RSV season, which generally occurs during fall, winter, and spring in most locations in the United States.

Palivizumab prophylaxis is not recommended for primary asthma prevention or to reduce subsequent episodes of wheezing.

Because 5 monthly doses of palivizumab at 15 mg/kg per dose will provide more than 6 months (>24 weeks) of serum palivizumab concentrations above the desired level for most children, administration of more than 5 monthly doses is not recommended within the continental United States ⁴⁶⁾. For qualifying infants who require 5 doses, a dose beginning in November and continuation for a total of 5 monthly doses will provide protection for most infants through April and is recommended for most areas of the United States. If prophylaxis is initiated in October, the fifth and final dose should be administered in February, which will provide protection for most infants through March. If prophylaxis is initiated in December, the fifth and final dose should be administered in April, which will provide protection for most infants through May.

Variation in the onset and offset of the RSV season in different regions of Florida may affect the timing of palivizumab administration. Data from the Florida Department of Health may be used to determine the appropriate timing for administration of the first dose of palivizumab for qualifying infants. Despite varying onset and offset dates of the RSV season in different regions of Florida, a maximum of 5 monthly doses of palivizumab should be adequate for qualifying infants for most RSV seasons in Florida.

Sporadic RSV infections occur throughout the year in most geographic locations. During times of low RSV prevalence (regardless of proportion of positive results), prophylaxis with palivizumab provides the least benefit because of the large number of children who must receive prophylaxis to prevent 1 RSV hospitalization.

Summary of American Academy of Pediatrics Guidance for Palivizumab ⁴⁷⁾:

• In the first year of life, palivizumab prophylaxis is recommended for infants born before 29 weeks, 0 days’ gestation.
• Palivizumab prophylaxis is not recommended for otherwise healthy infants born at or after 29 weeks, 0 days’ gestation.
• In the first year of life, palivizumab prophylaxis is recommended for preterm infants with chronic lung disease of prematurity, defined as birth at <32 weeks, 0 days’ gestation and a requirement for >21% oxygen for at least 28 days after birth.
• Clinicians may administer palivizumab prophylaxis in the first year of life to certain infants with hemodynamically significant heart disease.
• Clinicians may administer up to a maximum of 5 monthly doses of palivizumab (15 mg/kg per dose) during the RSV season to infants who qualify for prophylaxis in the first year of life. Qualifying infants born during the RSV season may require fewer doses. For example, infants born in January would receive their last dose in March.
• Palivizumab prophylaxis is not recommended in the second year of life except for children who required at least 28 days of supplemental oxygen after birth and who continue to require medical intervention (supplemental oxygen, chronic corticosteroid, or diuretic therapy).
• Monthly prophylaxis should be discontinued in any child who experiences a breakthrough RSV hospitalization.
• Children with pulmonary abnormality or neuromuscular disease that impairs the ability to clear secretions from the upper airways may be considered for prophylaxis in the first year of life.
• Children younger than 24 months who will be profoundly immunocompromised during the RSV season may be considered for prophylaxis.
• Insufficient data are available to recommend palivizumab prophylaxis for children with cystic fibrosis or Down syndrome.
• The burden of RSV disease and costs associated with transport from remote locations may result in a broader use of palivizumab for RSV prevention in Alaska Native populations and possibly in selected other American Indian populations.
• Palivizumab prophylaxis is not recommended for prevention of health care-associated RSV disease.

Preterm infants without chronic lung disease of prematurity or congenital heart disease

Palivizumab prophylaxis may be administered to infants born before 29 weeks, 0 days’ gestation who are younger than 12 months at the start of the RSV season. For infants born during the RSV season, fewer than 5 monthly doses will be needed.

Available data for infants born at 29 weeks, 0 days’ gestation or later do not identify a clear gestational age cutoff for which the benefits of prophylaxis are clear. For this reason, infants born at 29 weeks, 0 days’ gestation or later are not universally recommended to receive palivizumab prophylaxis. Infants 29 weeks, 0 days’ gestation or later may qualify to receive prophylaxis on the basis of congenital heart disease (congenital heart disease), chronic lung disease (chronic lung disease), or another condition.

Palivizumab prophylaxis is not recommended in the second year of life on the basis of a history of prematurity alone.

Some experts believe that on the basis of the data quantifying a small increase in risk of hospitalization, even for infants born earlier than 29 weeks, 0 days’ gestation, palivizumab prophylaxis is not justified.

Preterm infants with chronic lung disease

Prophylaxis may be considered during the RSV season during the first year of life for preterm infants who develop chronic lung disease of prematurity defined as gestational age <32 weeks, 0 days and a requirement for >21% oxygen for at least the first 28 days after birth.

During the second year of life, consideration of palivizumab prophylaxis is recommended only for infants who satisfy this definition of chronic lung disease of prematurity and continue to require medical support (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) during the 6-month period before the start of the second RSV season. For infants with chronic lung disease who do not continue to require medical support in the second year of life prophylaxis is not recommended.

Infants with hemodynamically significant congenital heart disease

Certain children who are 12 months or younger with hemodynamically significant congenital heart disease may benefit from palivizumab prophylaxis. Children with hemodynamically significant congenital heart disease who are most likely to benefit from immunoprophylaxis include infants with acyanotic heart disease who are receiving medication to control congestive heart failure and will require cardiac surgical procedures and infants with moderate to severe pulmonary hypertension.

Decisions regarding palivizumab prophylaxis for infants with cyanotic heart defects in the first year of life may be made in consultation with a pediatric cardiologist.

These recommendations apply to qualifying infants in the first year of life who are born within 12 months of onset of the RSV season.

The following groups of infants with congenital heart disease are not at increased risk of RSV infection and generally should not receive immunoprophylaxis:

• Infants and children with hemodynamically insignificant heart disease (eg, secundum atrial septal defect, small ventricular septal defect, pulmonic stenosis, uncomplicated aortic stenosis, mild coarctation of the aorta, and patent ductus arteriosus)
• Infants with lesions adequately corrected by surgery, unless they continue to require medication for congestive heart failure
• Infants with mild cardiomyopathy who are not receiving medical therapy for the condition
• Children in the second year of life

Because a mean decrease in palivizumab serum concentration of 58% was observed after surgical procedures that involve cardiopulmonary bypass, for children who are receiving prophylaxis and who continue to require prophylaxis after a surgical procedure, a postoperative dose of palivizumab (15 mg/kg) should be considered after cardiac bypass or at the conclusion of extracorporeal membrane oxygenation for infants and children younger than 24 months.

Children younger than 2 years who undergo cardiac transplantation during the RSV season may be considered for palivizumab prophylaxis.

Children with anatomic pulmonary abnormalities or neuromuscular disorder

No prospective studies or population-based data are available to define the risk of RSV hospitalization in children with pulmonary abnormalities or neuromuscular disease. Infants with neuromuscular disease or congenital anomaly that impairs the ability to clear secretions from the upper airway because of ineffective cough are known to be at risk for a prolonged hospitalization related to lower respiratory tract infection and, therefore, may be considered for prophylaxis during the first year of life.

Immunocompromised children

No population based data are available on the incidence of RSV hospitalization in children who undergo solid organ or hematopoietic stem cell transplantation. Severe and even fatal disease attributable to RSV is recognized in children receiving chemotherapy or who are immunocompromised because of other conditions, but the efficacy of prophylaxis in this cohort is not known. Prophylaxis may be considered for children younger than 24 months of age who are profoundly immunocompromised during the RSV season.

Children with Down syndrome

Limited data suggest a slight increase in RSV hospitalization rates among children with Down syndrome. However, data are insufficient to justify a recommendation for routine use of prophylaxis in children with Down syndrome unless qualifying heart disease, chronic lung disease, airway clearance issues, or prematurity (<29 weeks, 0 days’ gestation) is present.

Children with Cystic Fibrosis

Routine use of palivizumab prophylaxis in patients with cystic fibrosis, including neonates diagnosed with cystic fibrosis by newborn screening, is not recommended unless other indications are present. An infant with cystic fibrosis with clinical evidence of chronic lung disease and/or nutritional compromise in the first year of life may be considered for prophylaxis. Continued use of palivizumab prophylaxis in the second year may be considered for infants with manifestations of severe lung disease (previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest radiography or chest computed tomography that persist when stable) or weight for length less than the 10th percentile.

Recommendations for timing of prophylaxis for Alaska Native and American Indian Infants

On the basis of the epidemiology of RSV in Alaska, particularly in remote regions where the burden of RSV disease is significantly greater than the general US population, the selection of Alaska Native infants eligible for prophylaxis may differ from the remainder of the United States. Clinicians may wish to use RSV surveillance data generated by the state of Alaska to assist in determining onset and end of the RSV season for qualifying infants.

Limited information is available concerning the burden of RSV disease among American Indian populations. However, special consideration may be prudent for Navajo and White Mountain Apache infants in the first year of life.

Discontinuation of palivizumab prophylaxis among children who experience breakthrough RSV hospitalization

If any infant or young child receiving monthly palivizumab prophylaxis experiences a breakthrough RSV hospitalization, monthly prophylaxis should be discontinued because of the extremely low likelihood of a second RSV hospitalization in the same season (<0.5%).

Use of palivizumab in the second year of life

Hospitalization rates attributable to RSV decrease during the second RSV season for all children. A second season of palivizumab prophylaxis is recommended only for preterm infants born at <32 weeks, 0 days’ gestation who required at least 28 days of oxygen after birth and who continue to require supplemental oxygen, chronic systemic corticosteroid therapy, or bronchodilator therapy within 6 months of the start of the second RSV season.

Prevention of health care-associated RSV disease

No rigorous data exist to support palivizumab use in controlling outbreaks of health care-associated disease, and palivizumab use is not recommended for this purpose. Infants in a neonatal unit who qualify for prophylaxis because of chronic lung disease, prematurity, or congenital heart disease may receive the first dose 48 to 72 hours before discharge to home or promptly after discharge.

Strict adherence to infection-control practices is the basis for reducing health care-associated RSV disease.

RSV signs and symptoms

Early symptoms of RSV

RSV may not be severe when it first starts. However, it can become more severe a few days into the illness. Early symptoms of RSV may include:

• runny nose
• decrease in appetite
• cough, which may progress to wheezing

Signs and symptoms of RSV infection usually include:

• Runny nose
• Decrease in appetite
• Coughing
• Sneezing
• Fever
• Wheezing

These symptoms usually appear in stages and not all at once. In very young infants with RSV, the only symptoms may be irritability, decreased activity, and breathing difficulties.

RSV can also cause more severe infections such as bronchiolitis, an inflammation of the small airways in the lung, and pneumonia, an infection of the lungs. It is the most common cause of bronchiolitis and pneumonia in children younger than 1 year of age.

When an adult gets RSV infection, they typically have mild cold-like symptoms. But RSV can sometimes lead to serious conditions such as:

• Pneumonia (infection of the lungs)
• More severe symptoms for people with asthma
• More severe symptoms for people with chronic obstructive pulmonary disease (COPD) (a chronic disease of the lungs that makes it hard to breathe)
• Congestive heart failure (when the heart can’t pump blood and oxygen to the body’s tissues)

Older adults who get very sick from RSV may need to be hospitalized. Some may even die. Older adults are at greater risk than young adults for serious complications from RSV because our immune systems weaken when we are older.

RSV in very young infants

Infants who get an RSV infection almost always show symptoms. This is different from adults who can sometimes get RSV infections and not have symptoms. In very young infants (less than 6 months old), the only symptoms of RSV infection may be:

• irritability
• decreased activity
• decreased appetite
• apnea (pauses while breathing)

Fever may not always occur with RSV infections.

RSV in older adults and adults with chronic medical conditions

Older children and adults who get infected with RSV usually have mild or no symptoms. Symptoms are usually consistent with an upper respiratory tract infection which can include rhinorrhea, pharyngitis, cough, headache, fatigue, and fever. RSV disease usually lasts less than five days.

Some adults, however, may have more severe symptoms consistent with a lower respiratory tract infection, such as pneumonia. Those at high risk for severe illness from RSV include:

• older adults, especially those 65 years and older
• adults with chronic lung or heart disease
• adults with weakened immune systems

RSV can sometimes also lead to exacerbation of serious conditions such as:

• asthma
• chronic obstructive pulmonary disease (COPD)
• congestive heart failure

RSV diagnosis

Clinical symptoms of RSV are nonspecific and can overlap with other viral respiratory infections, as well as some bacterial infections. Several types of laboratory tests are available for confirming RSV infection. These tests may be performed on upper and lower respiratory specimens.

The 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

Less commonly used tests include:

• viral culture
• serology, which is usually only used for research and surveillance studies

Some tests can differentiate between RSV subtypes (A and B), but the clinical significance of these subtypes is unclear. Consult your laboratorian for information on what type of respiratory specimen is most appropriate to use.

For infants and young children

Both real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) and antigen detection tests are effective methods for diagnosing RSV infection in infants and young children. The RSV sensitivity of antigen detection tests generally ranges from 80% to 90% in this age group. Healthcare professionals should consult experienced laboratorians for more information on interpretation of results.

For older children, adolescents, and adults

Healthcare professionals should use highly sensitive rRT-PCR assays when testing older children and adults for RSV. rRT-PCR assays are now commercially available for RSV. The sensitivity of these assays often exceeds the sensitivity of virus isolation and antigen detection methods. Antigen tests are not sensitive for older children and adults because they may have lower viral loads in their respiratory specimens. Healthcare professionals should consult experienced laboratorians for more information on interpretation of results.

Treatment for RSV

Treatment for RSV falls into three categories: supportive care, immune prophylaxis, and antiviral medication ⁴⁸⁾. The majority of RSV and bronchiolitis cases require no specific medical intervention, and many attempted treatments throughout history are ineffective. Vaccines for RSV and therapeutic interventions in RSV remain a target of intense scientific interest.

The mainstay of treatment for patients with RSV is supportive care. The spectrum of supportive care includes nasal suction and lubrication to provide relief from nasal congestion, antipyretics for fever, assisted hydration in the event of dehydration (assistance may be by mouth, by nasogastric tube, or intravenously), and oxygen for patients experiencing hypoxia. Patients with severe presentation and respiratory compromise/failure may require ventilatory support in the form of a high-flow nasal cannula, continuous positive airway pressure (CPAP), or intubation, and mechanical ventilation. Hospitalization is recommended for patients who are experiencing or are at risk for moderate to severe disease, patients requiring supplemental fluids, and patients requiring respiratory support.

Effective passive immune prophylaxis for RSV exists in the form of palivizumab, a humanized murine monoclonal antibody with activity against the RSV membrane fusion protein required for fusion with host cell membranes. Palivizumab must be administered monthly for the duration of the RSV season. Palivizumab is relatively expensive and is the subject of some debate regarding cost-effectiveness. The American Academy of Pediatrics publishes guidelines regarding which patients are candidates for palivizumab and its discontinuation in breakthrough infection, and we refer readers to those guidelines for specific recommendations regarding palivizumab eligibility (see above under prophylaxis). Broadly, these recommendations include prophylaxis for children in the first year of life with: prematurity less than or equal to 29 weeks gestational age, chronic lung disease of prematurity, congenital heart disease, or neuromuscular disorders.

There is a single antiviral medication approved for use against RSV in the United States, ribavirin. It is a nucleoside analog with application in several RNA viruses, and it shows in vitro activity against RSV and may be administered in aerosolized form. However, its use in RSV remains controversial due to expense, questions of danger to exposed health care providers, and questions of efficacy, specifically regarding mortality, length of mechanical ventilation, and length of hospital stay. Ribavirin’s routine use is discouraged, but it may be considered on a case-by-case basis.

Many other treatment modalities for bronchiolitis have been tried in the past, and all others have failed to show broad, reproducible efficacy on clinically significant outcomes in RSV and bronchiolitis. These include albuterol, racemic epinephrine, steroids, hypertonic saline, antibiotics, and chest physical therapy, and routine use of these interventions is not recommended ⁴⁹⁾.

RSV prognosis

The majority of children with RSV have an excellent outcome. Even those who need admission are usually discharged in several days. However, high-risk infants with other co-morbidities may require longer admission and some may even require mechanical ventilation. The overall mortality for RSV is less than 1%, and in the United States, there are less than 400 deaths attributed to RSV each year. Infants with congenital heart disease, prematurity or chronic lung disease tend to have the highest mortality. Further infants who are immunocompromised also tend to have longer admissions compared to normal infants. In the long run, some infants with RSV may develop wheezing, but this is debatable. Recent studies do not show an increased risk of asthma ⁵⁰⁾.