Respiratory syncytial virus infection: Clinical features and diagnosis

INTRODUCTION — Respiratory syncytial virus (RSV) causes acute respiratory tract illness in persons of all ages. The clinical manifestations vary with age, health status, and whether the infection is primary or secondary.

The epidemiology, microbiology, clinical manifestations, and diagnosis of RSV infection will be presented here. The treatment and prevention of RSV infection and the treatment of bronchiolitis are discussed separately. (See "Respiratory syncytial virus infection: Treatment" and "Respiratory syncytial virus infection: Prevention in infants and children" and "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)

EPIDEMIOLOGY

●Seasonality – RSV typically causes seasonal outbreaks throughout the world. In the northern hemisphere, these usually occur from October or November to April or May, with a peak in January or February [1-3]. In the southern hemisphere, wintertime epidemics occur from May to September, with a peak in May, June, or July. In tropical and semitropical climates, the seasonal outbreaks usually are associated with the rainy season. The epidemic peaks are not as sharp as in temperate climates, and in some settings RSV can be isolated in as many as eight months of the year [4-7].

Disruption of the typical seasonal pattern of RSV may result in off-season outbreaks. During the coronavirus disease 2019 (COVID-19) pandemic, mitigation measures (eg, mask wearing, physical distancing, school closure) were associated with marked reductions in non-COVID-19 respiratory infections in children, including RSV, during the winter season [8-15]. However, interseasonal RSV activity (eg, in the spring and early summer) has subsequently been described in both the Northern and Southern hemispheres, which may be due in part to relaxation of mitigation measures and waning immunity [8,9,16-18]. As an example, in the Northern hemisphere, RSV was relatively absent during the typical 2020-2021 season, then appeared in May 2021. Similarly, minimal RSV occurred in the typical 2021-2022 season and returned in September 2022, peaking in early November. Thus, two RSV outbreaks occurred over three years, 16 to 18 months apart; the timing of future seasonal patterns is not yet known [19].

●Morbidity and mortality in children – RSV causes acute respiratory tract illness in persons of all ages. Almost all children are infected by two years of age, and reinfection is common [20].

•Morbidity – RSV is the most common cause of lower respiratory tract infection (LRTI) in children <1 year of age [1]. In a systematic review and meta-analysis, the global annual rate of RSV hospitalization among children <5 years was 4.4 per 1000 (95% CI 3.0-6.4) [21]. RSV hospitalization rates were highest among children <6 months (20.0 per 1000, 95% CI 0.7-41.3) and premature infants <1 year (63.9 per 1000, 95% CI 37.5-109.7). In an international multicenter case-control study, RSV was the most common pathogen isolated from children age 1 through 59 months hospitalized for severe pneumonia in Africa and Asia, accounting for 31 percent of cases [22].

In a prospective population-based study in the United States (2015-2016 season), the RSV hospitalization rate was 2.9 per 1000 children <5 years of age, 6.3 per 1000 children <2 years of age, and 14.7 per 1000 children <6 months of age [23]. In a prospective European multicenter birth cohort study (2017-2020 seasons), 18 per 1000 of healthy full-term infants were hospitalized for RSV during their first year of life [24].

Hospitalization for RSV infection also may occur in children >5 years [25], but these children often have underlying medical problems (eg, neurologic disease, immunodeficiency).

RSV is also a common cause of outpatient visits for children <24 months of age. In active surveillance at three sites in the United States (2004 to 2009), approximately 20 percent of 3339 children <24 months of age seen in an emergency department or pediatric clinic for acute respiratory infection or fever who were tested for RSV tested positive [26]. The annual incidence of RSV was 59.6 per 1000 (95% CI 50.9-68.3) among those who were seen in emergency departments, and 205.7 per 1000 (95% CI 169.5-241.9) among those who were seen in outpatient clinics. The incidence peaked at four to five months of age.

•Mortality – RSV is an important cause of death in infants and young children. Globally, RSV is estimated to cause as many as 2.3 percent of deaths among neonates 0 to 27 days of age, 6.7 percent of deaths among infants 28 to 364 days of age, and 1.6 percent of deaths among children one through four years of age [27]. Among infants 28 to 364 days of age, RSV is estimated to cause more deaths than any other single infectious agent with the exception of malaria. In resource-limited settings, RSV mortality occurs primarily in term infants [28]. If access to advanced medical care is limited, death may occur at home [29].

In the United States, the estimated annual RSV-associated pneumonia mortality rate is 3.1 per 100,000 person years in children <1 year [30]. In resource-rich countries, most pediatric RSV deaths occur in children born prematurely and those with underlying cardiopulmonary disease or other chronic conditions (eg, immune deficiency) [28,31]. In a review of 79 pediatric RSV-associated deaths that occurred in Canada between 2003 and 2013, the median age at death was 11 months (range <1 month to 16 years), approximately 20 percent had no known risk factors for severe RSV infection, and 37 percent of fatal RSV infections were acquired in the hospital (ie, with symptom onset >72 hours after admission or <72 hours after hospital discharge from previous admission) [32].

●Morbidity and mortality in adults

•Healthy adults <50 years of age – Healthy adults are infected with RSV repeatedly throughout their lives and typically have symptoms restricted to the upper respiratory tract. In a study of 256 military trainees with respiratory symptoms, RSV infection was identified in 11 percent of patients through acute and convalescent serologic testing and real-time polymerase chain reaction (PCR) [33].

•Adults ≥50 years of age and adults with underlying conditions

-Morbidity – RSV is an important and often unrecognized cause of LRTI in older adults and immunocompromised adults [34-40].

In a prospective cohort study of respiratory illnesses in 608 healthy adults ≥65 years and 540 high-risk adults (ie, those with chronic heart or lung disease, the annual incidence of RSV was 5.5 percent (ranging from 3 to 7 percent in the healthy older adults and 4 to 10 percent in the high risk group) [41]. In another prospective study, RSV was detected in 11 percent of outpatients ≥60 years of age with acute respiratory illness [42].

In another prospective study, the average annual hospitalization rate for RSV infection among adults ≥50 years of age was 15 per 10,000 residents [39].

-Mortality – RSV is an important cause of death in adults older than 50 years. In a systematic review of observational studies, the mortality rate among adults ≥50 years of age who were hospitalized with RSV was 6 to 8 percent [43].

RISK FACTORS — Patients at risk for severe lower respiratory tract disease include:

●Infants younger than six months of age [44], particularly those who are born during the first half of the RSV season, those attending daycare [45,46], and those with older siblings (who may have asymptomatic RSV infection) [47,48] (see 'Transmission and incubation period' below)

●Infants and children with underlying lung disease, such as chronic lung disease (bronchopulmonary dysplasia, cystic fibrosis) [49-51]

●Infants born before 35 weeks gestation [44,48,52-54]

●Infants and children with congenital heart disease [55]

●Infants exposed to secondhand smoke [56-58]

●Human immunodeficiency virus (HIV)-exposed, uninfected infants [59-61]

●Patients with Down syndrome [50,62]

●Immunocompromised patients (eg, severe combined immunodeficiency, leukemia, or hematopoietic cell or lung transplant) [50,63-68]

●Children <5 years with social vulnerability (eg, lack of running water in the home, young maternal age) [29,69]

●Patients of any age group with persistent asthma

●Adults with cardiopulmonary disease [42,68,70,71]

●Residence at altitude >2500 m [72]

●Institutionalized older adults [34]

●Older adult patients with chronic pulmonary disease or functional disability [73]

Studies evaluating potential genetic predisposition to severe RSV disease have revealed associations with polymorphisms in cytokine- and chemokine-related genes including interleukin (IL)-4 and its receptor, IL-8, IL-10, IL-13, and chemokine receptor (CCR)5 [74-79]. Genetic polymorphisms in genes related to potential virus-cell surface interactions or cell signaling such as toll-like receptor (TL)-4, chemokine receptor 1 (CX3CR1), surfactant protein (SP)-A, and SP-D also have been associated with severe RSV disease [80-85]. Additional studies are necessary before these genetic polymorphisms can be used to predict severe RSV disease.

MICROBIOLOGY — RSV is a single-stranded, negative-sense ribonucleic acid (RNA) virus and a member of the Pneumoviridae family [86]. Two subtypes, A and B, are simultaneously present in most outbreaks, with A subtypes typically causing more severe disease [87-91]. Several distinct genotypes within these subtypes predominate within a community; the dominant strains shift yearly, perhaps accounting for frequent reinfections [87,92].

TRANSMISSION AND INCUBATION PERIOD

●Transmission – Transmission of RSV is primarily by inoculation of nasopharyngeal or ocular mucous membranes after contact with virus-containing secretions or fomites [93]. Direct contact is the most common route of transmission, but large droplet aerosols also have been implicated [94-97]. RSV can survive for several hours on hands and fomites [87]. Hand washing and contact precautions are therefore important measures to prevent health care-associated spread. Studies of transmission dynamics suggest that infection of infants most often follows infection of older siblings [98]. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Infection control in the health care setting'.)

Shedding of RSV was examined in a prospective study that evaluated nasopharyngeal swab specimens from a cohort of 47 households (493 individuals) during a seasonal outbreak of RSV [47,98,99]. Among 205 RSV infection episodes in 179 individuals from 40 households, 42 percent were asymptomatic [47]. The average duration of viral shedding detected with polymerase chain reaction was 11 days [99]. The duration of shedding varied with age and other factors, and was increased in primary infection. When detected with viral culture or immunofluorescence, the period of viral shedding is usually shorter – three to eight days [100,101] – but it may last up to four weeks in young infants and several months in children with HIV infection [66].

●Incubation period – The incubation period is usually four to six days (range two to eight days) [20].

IMMUNITY — Although virtually all individuals have been infected with RSV by age two years, previous infection with RSV does not appear to protect against reinfection, even in patients with high titers of specific antibody [102].

Several observations suggest that humoral immunity is more important in ameliorating the severity of RSV infection than in preventing disease. Although individuals can be infected with RSV more than once, subsequent infections usually are milder whether they occur in the same season or in different years [103]. Although transplacentally acquired RSV antibody does not protect infants against infection, infants with high antibody titers usually have milder symptoms restricted to the upper respiratory tract [104]. In a population-based study, lower mean cord blood antibody titers were associated with increased risk of RSV hospitalization before age six months [105]. Similarly, older adults with lower immunoglobulin G (IgG) anti-RSV titers are more likely to develop symptomatic RSV infection than are similar patients with higher titers [73].

The role of cellular immunity against RSV in humans is not well defined [106]. Patients with severe combined immunodeficiency syndrome and those who have undergone allogenic hematopoietic cell transplantation often have fatal RSV disease and difficulty clearing virus, suggesting the importance of cluster of differentiation 8 (CD8) T cells for controlling virus spread [107]. This may also be an important mechanism of immunity in older adults [108].

PATHOGENESIS — After replicating in the nasopharynx, RSV infects the small bronchiolar epithelium, sparing the basal cells, then extends to the type 1 and 2 alveolar pneumocytes in the lung, presumably by cell-to-cell spread or aspiration of secretions; lower respiratory tract infection occurs one to three days later [109,110].

Pathologic findings of RSV include necrosis of epithelial cells, occasional proliferation of the bronchiolar epithelium, infiltration of monocytes and T cells centered on bronchial and pulmonary arterioles, and infiltration of neutrophils between the vascular structures and small airways [109,111]. This leads to airway obstruction, air trapping, and increased airway resistance, and also is associated with a finding of neutrophilia in bronchoalveolar lavage [112].

RSV is highly restricted to the respiratory epithelium and is shed apically into the lumen of the airways. In very rare cases, RSV may be recovered from extrapulmonary tissues, such as liver [113], cerebrospinal fluid [114], or pericardial fluid [115].

The immune response to RSV, especially cytokine and chemokine release, appears to play a role in the pathogenesis and severity of bronchiolitis [116-121]. The cytokines interleukin (IL)-8, IL-6, tumor necrosis factor (TNF)-alpha, and IL-1 beta can be detected in airway secretions of infected children [122-124], and IL-6 levels correlate with severe disease. Chemokines identified in respiratory tract secretions of children include chemokine ligand (CCL)3 (macrophage inflammatory protein-1 [MIP-1 alpha]), CCL2 (monocyte chemoattractant protein-1 [MCP-1]), CCL11 (eotaxin), and CCL5 (RANTES [regulated on activation, normal T cell expressed and secreted]) [117,125], but only the beta-chemokines, particularly MIP-1 alpha, are associated with severe disease [117,125,126]. RSV infection of explanted polarized, differentiated respiratory epithelium in tissue culture elicits IL-8 and CCL5 [127], suggesting these epithelium-derived factors may be important for attracting inflammatory cells to the infected lung. Soluble factors associated with severe disease are primarily derived from cells associated with the immune response. It is not fully resolved whether the cytokines and chemokines associated with severe disease are the cause of disease or the byproduct of higher RSV antigen load stimulating a stronger inflammatory response.

CLINICAL MANIFESTATIONS — The clinical manifestations vary with patient's age, health status, and whether the infection is primary or secondary.

Infants and young children — Infants and young children with primary infections usually present with lower respiratory tract infection ([LRTI]; bronchiolitis or pneumonia) [128]. RSV can also cause apnea in infants.

Lower respiratory tract disease — RSV can cause severe lower respiratory tract disease, including bronchiolitis, bronchospasm, pneumonia, and acute respiratory failure in children [22]. Lower respiratory tract disease usually occurs with primary infection and may occur in more than 50 percent of second infections [103,128]. Although disease severity diminishes after the third infection approximately one-fourth have signs of LRTI [129].

Approximately 20 percent of infants develop RSV-associated wheezing during the first year of life; 2 to 3 percent require hospitalization [44,128]. The clinical features and course of bronchiolitis, which may be caused by viruses other than RSV, are discussed in detail separately. (See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Clinical features'.)

As with other types of pulmonary disease, RSV infection of the lower respiratory tract may be associated with inappropriate secretion of antidiuretic hormone (ADH), resulting in hyponatremia, particularly in patients who require mechanical ventilation [130-132]. Hyponatremia also may result from inappropriate administration of hypotonic intravenous fluids to critically ill children. (See "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)", section on 'Pulmonary disease' and "Treatment of hypovolemia (dehydration) in children in resource-abundant settings".)

Apnea — RSV can cause severe apnea, which may be the presenting symptom in infants admitted to the hospital with RSV [133-138]. Although the mechanism is unknown [139,140], RSV has been postulated to alter the sensitivity of laryngeal chemoreceptors and reinforce reflex apnea [141]. RSV-associated apnea has been speculated to be associated with sudden infant death syndrome [142]. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Environmental triggers'.)

It is difficult to quantify the risk of apnea in infants hospitalized with RSV infection. In a systematic review of cohort studies that included 5575 infants hospitalized with RSV bronchiolitis, the incidence of apnea ranged from 1.2 to 23.8 percent [138]. In studies that excluded children with serious underlying illness, the risk of apnea was <5 percent. In those that assessed gestational age, the incidence of apnea was increased in preterm compared with term infants. In a subsequent prospective multicenter study that included 2207 infants hospitalized with bronchiolitis (not limited to RSV), the incidence of apnea was 5 percent; the risk of apnea was not increased with RSV compared with other viral pathogens [143]. (See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Apnea'.)

Pulmonary sequelae — RSV infection usually is a self-limited process that results in no apparent long-term pulmonary sequelae. However, it may be associated with persistent decreased pulmonary function and chronic obstructive pulmonary disease in adulthood [144].

In addition, RSV infection in infancy has been associated with recurrent wheezing in some patients. (See "Role of viruses in wheezing and asthma: An overview".)

Older children and adults

●Upper respiratory tract disease – Repeat RSV infections occur frequently in children and young adults and generally cause upper respiratory tract symptoms. Signs include cough, coryza, rhinorrhea, and conjunctivitis. Compared with other respiratory viruses, RSV is more likely to cause sinus and ear involvement [129]. Disease severity usually diminishes after the third infection.

●Lower respiratory tract disease – Repeat RSV infections in older children and adults also may cause tracheobronchitis or other types of lower respiratory tract disease (eg, pneumonia, bronchitis, exacerbation of asthma or chronic obstructive pulmonary disease), particularly in older adults and patients in long-term care facilities [145]. In a prospective study, approximately one-fourth of 211 adults with RSV infection had signs of lower respiratory tract disease [129].

RSV infection in adults may cause short-term airway reactivity [146]. Wheezing and shortness of breath have been described in adult patients with and without underlying comorbidities or hyperreactive airways [33,34]. Wheezing occurs in approximately 35 percent of older adult patients with RSV infection [147].

Hospitalization for RSV infection in adults may be complicated by cardiovascular events (eg, worsening heart failure, acute coronary syndrome, arrhythmia) [71]. Compared with influenza in adults ≥65 years of age, RSV appears to be associated with increased risk of length of stay ≥7 days, exacerbation of chronic obstructive pulmonary disease, and increased mortality within one year [38].

Immunocompromised patients — RSV pneumonia leading to respiratory failure is an important cause of acute morbidity and mortality in the immunocompromised host. Among hematopoietic cell transplant recipients, mortality rates of 70 to 100 percent have been reported [148,149].

Long-term pulmonary sequelae in immunocompromised patients have not been adequately studied. However, chronic pulmonary dysfunction as a result of RSV infection does not appear to be a problem in lung or renal transplant patients [150,151].

RADIOGRAPHIC FINDINGS — Radiographic findings vary depending upon the clinical syndrome and are discussed separately:

●Bronchiolitis (image 1) (see "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Radiographic features')

●Croup (image 2A-B) (see "Croup: Clinical features, evaluation, and diagnosis", section on 'Radiographs')

●Pneumonia (see "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Radiologic evaluation' and "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults", section on 'Chest imaging findings')

DIAGNOSIS

Clinical suspicion — RSV bronchiolitis should be suspected in infants with compatible clinical and epidemiologic features (eg, age <12 months, lower respiratory tract disease, winter season, known circulation of RSV) [152]. RSV should also be suspected in patients hospitalized with acute lower respiratory tract disease (eg, pneumonia, bronchitis, exacerbation of asthma or chronic obstructive pulmonary disease) if they are immunocompromised or ≥50 years of age. However, other respiratory pathogens share the clinical patterns of RSV, and clinical features are insufficient to reliably distinguish RSV from these infections. (See 'Differential diagnosis' below.)

Clinical suspicion of RSV is usually sufficient for previously healthy infants and young children with typical bronchiolitis. Identification of RSV in such patients is unlikely to affect management. (See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Approach to testing'.)

Laboratory confirmation — Laboratory diagnosis of RSV should be pursued if identification of RSV will affect clinical management (ie, if it will affect decisions about antimicrobial therapy, continuation of palivizumab prophylaxis, additional evaluation, infection control etc). This is often the case for children hospitalized with acute lower respiratory tract disease, immunocompromised patients, immune-competent patients with recurrent respiratory illnesses, and immune-competent older adults who are hospitalized with acute lower respiratory tract disease.

●Obtaining samples – The laboratory diagnosis of RSV is made by analysis of respiratory secretions. In healthy children, a nasal wash usually provides the best yield, but a nasopharyngeal swab or midturbinate nasal swab may be adequate if a nasal wash is not possible [153-155].

In patients who are intubated or are undergoing bronchoscopy, a tracheal aspirate or bronchoalveolar lavage should be obtained. This is particularly true for immune-compromised adults in whom lower respiratory secretions have a higher rate of positivity than nasal secretions [145,156].

●Approach to testing – When confirmation of RSV infection is necessary, we prefer polymerase chain reaction (PCR)-based assays if they are available [157]. PCR-based assays have high sensitivity and are not affected by passively administered antibody to RSV [158,159]. If PCR-based assays are not available, rapid antigen detection tests (RADTs) are a reasonable alternative, although false negative results may occur, particularly in adult patients who shed less virus from infected cells than infants. Some laboratories perform initial RADT and confirm negative results with PCR [160].

●Testing methods

•Viral culture – The standard for definitive diagnosis is isolation of RSV in human epithelial type 2 (HEp-2) cells. Identification of typical plaque morphology with syncytium formation and immunofluorescent staining confirms the diagnosis. However, identification by culture can take from four days to two weeks.

•Polymerase chain reaction-based assays – PCR-based assays for detection of RSV are available in most children's hospitals and approximately 50 percent of hospitals that care exclusively for adults or for both adults and children [160]. PCR-based assays typically are included as part of a multiplex PCR assay that can detect multiple respiratory pathogens [161]. Multiplex PCR-based assays are more expensive than RADT. They also usually have a longer turnaround time than RADT, but some commercially available PCR-based assays provide results in <3 hours [162].

Detection of RSV with PCR-based assays is correlated with symptomatic infection. In a prospective study that compared the prevalence of viruses identified with PCR-based assays in patients with community-acquired pneumonia (CAP) and asymptomatic controls, RSV was more prevalent in children with CAP than asymptomatic controls (26.6 versus 1.9 percent in children, attributable fraction 93 percent); RSV was not detected in any of 238 asymptomatic adults [163]. Similarly, in a multicenter case control study, RSV was isolated from 36 percent of children age 1 through 11 months and 17 percent of children age 1 through 4 years who were hospitalized with severe pneumonia compared with approximately 3 percent of asymptomatic controls [22].

•Rapid antigen detection test – RADT for RSV can be performed in less than 30 minutes. They have relatively high sensitivity and specificity in children and high specificity in adults. Although they are less sensitive than PCR-based assays in adults, they continue to be used in approximately 50 percent of laboratories that perform tests on samples from adults only or from adults and children [160].

Palivizumab prophylaxis may interfere with some RADT, leading to false-negative results [159]. False-negative results also may occur independent of palivizumab prophylaxis, particularly in adult patients. In a meta-analysis of 71 studies, the sensitivity of RADT was 80 percent (95% CI 76-83 percent) and the specificity was 97 percent (95% CI 96-98 percent) [158]. In subgroup analysis, sensitivity was higher in children (81 percent, 95% CI 78-84 percent) than in adults (29 percent, 95% CI 11-48 percent), but the pooled sensitivity in adults was based on only four studies (738 patients).

•Serology – Diagnostic serology is not helpful in the evaluation and management of RSV infection because of maternal antibody in infants and a stable and sustained level of RSV-specific antibody in older children and adults (related to repeated infections) [157].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of RSV infection includes other pathogens that cause similar clinical syndromes. Microbiologic testing is necessary to differentiate RSV from other respiratory pathogens.

●Bronchiolitis in infants and children – Other pathogens that cause bronchiolitis in infants and children include parainfluenza virus, metapneumovirus, influenza virus, rhinovirus, coronavirus, human bocavirus, and adenovirus. In severe cases of RSV bronchiolitis, the possibility of coinfection with other viruses (eg, adenovirus, influenza), mycoplasma, or bacteria, including Bordetella pertussis, should be considered [164-167]. (See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Microbiology'.)

●Pneumonia in children – Other pathogens that cause community-acquired pneumonia in children include typical and atypical bacteria and other viruses (table 1). (See "Pneumonia in children: Epidemiology, pathogenesis, and etiology", section on 'Etiologic agents'.)

●Bronchial reactivity – Other viruses, particularly rhinovirus, can cause bronchial reactivity (including asthma exacerbation) in children and adults (table 2). (See "Role of viruses in wheezing and asthma: An overview", section on 'Specific viruses'.)

●Lower respiratory tract disease in older adults and immunocompromised patients – Other pathogens that cause lower respiratory tract disease (eg, pneumonia, bronchitis) in older adults and immunocompromised patients include other viruses (eg, influenza, rhinovirus, parainfluenza virus) and typical and atypical bacteria (eg, S. pneumoniae, Mycoplasma pneumoniae). (See "Acute bronchitis in adults", section on 'Microbiology' and "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiology'.)

Additional pathogens that may cause lower respiratory tract infections in immunocompromised patients include other viruses (eg, cytomegalovirus, varicella), fungi (eg, aspergillus, cryptococcus), and parasites (eg, Strongyloides, toxoplasmosis). (See "Epidemiology of pulmonary infections in immunocompromised patients", section on 'Pathogens'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bronchiolitis in infants and children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topics (see "Patient education: Bronchiolitis and RSV in children (The Basics)")

●Beyond the Basics topics (see "Patient education: Bronchiolitis and RSV in infants and children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology and risk factors – Respiratory syncytial virus (RSV) causes seasonal outbreaks of respiratory tract illness throughout the world, usually during the winter season. (See 'Epidemiology' above.)

RSV is the most common cause of lower respiratory tract infection (LRTI) in children younger than one year and the most common cause of medically attended LRTI in children younger than five years. Almost all children are infected by two years of age, and reinfection is common. (See 'Epidemiology' above.)

RSV is also an important and often unrecognized cause of LRTI in older adults and immunocompromised patients. (See 'Epidemiology' above.)

RSV has the potential to cause severe LRTI in certain high-risk groups, including young, premature infants with chronic lung disease, congenital heart disease, or Down syndrome; patients with persistent asthma; patients who are immunocompromised; and older adults. (See 'Risk factors' above.)

●Clinical manifestations – The clinical manifestations of RSV infection vary with age, health status, and whether the infection is primary or secondary.

•Infants and young children with primary infections generally present with LRTI. Apnea may be the presenting symptom in hospitalized infants. RSV infection usually is self-limited, but has been associated with recurrent wheezing in some patients. (See 'Infants and young children' above.)

•Older children and adults with secondary infections typically have upper respiratory tract symptoms but may develop LRTI, particularly if they are older adults or immunocompromised. (See 'Older children and adults' above and 'Immunocompromised patients' above.)

●Diagnosis

•Clinical suspicion – RSV bronchiolitis should be suspected in infants with compatible clinical and epidemiologic features (eg, age <12 months, lower respiratory tract disease, winter season, known circulation of RSV). Laboratory confirmation is not necessary for previously healthy infants and young children with typical bronchiolitis. (See 'Clinical suspicion' above and "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Clinical diagnosis'.)

RSV should also be suspected in patients hospitalized with acute lower respiratory tract disease (eg, pneumonia, bronchitis, exacerbation of asthma or chronic obstructive pulmonary disease) if they are immunocompromised or ≥50 years of age. (See 'Clinical suspicion' above.)

•Laboratory confirmation – Laboratory diagnosis of RSV should be pursued in if identification of RSV will affect clinical management (ie, if it will affect decisions about antimicrobial therapy, continuation of palivizumab prophylaxis, additional evaluation, infection control etc). This is often the case for children hospitalized with acute lower respiratory tract disease, immunocompromised patients, immune-compete patients with recurrent respiratory illnesses, and immune competent older adults who are hospitalized with acute respiratory illness. (See 'Laboratory confirmation' above.)

When confirmation of RSV infection is necessary, we prefer polymerase chain reaction (PCR)-based assays if they are available. PCR-based assays have high sensitivity and are not affected by passively administered antibody to RSV. If PCR-based assays are not available, rapid antigen detection tests are a reasonable alternative, although false negative results are common in adult patients. (See 'Laboratory confirmation' above.)

●Differential diagnosis – The differential diagnosis of RSV infection includes other pathogens that cause similar clinical syndromes (eg, parainfluenza virus, metapneumovirus, influenza virus, rhinovirus, coronavirus, bocavirus, adenovirus). (See 'Differential diagnosis' above.)