Respiratory syncytial virus infection: Treatment

Authors
Frederick E Barr, MD
Barney S Graham, MD, PhD
Section Editors
Morven S Edwards, MD
George B Mallory, MD
Deputy Editor
Mary M Torchia, MD
Disclosures: Frederick E Barr, MD Nothing to disclose. Barney S Graham, MD, PhD Nothing to
disclose. Morven S Edwards, MD Grant/Research/Clinical Trial Support: Pfizer Inc. [Group B Streptococcus].
Consultant/Advisory Boards: Novartis Vaccines [Group B Streptococcus]. George B Mallory, MD Nothing to
disclose. Mary M Torchia, MD Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform to
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All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Aug 2015. | This topic last updated: Jul 28, 2015.

INTRODUCTION — Respiratory syncytial virus (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 [1]. The clinical manifestations vary with age, health status, and whether the infection
is primary or secondary.

The treatment of respiratory syncytial virus infection in infants, children, and adults will be
discussed here. The epidemiology, microbiology, clinical manifestations, diagnosis, and
prevention of RSV infection are discussed separately. (See "Respiratory syncytial virus
infection: Clinical features and diagnosis" and "Respiratory syncytial virus infection:
Prevention".)

OVERVIEW — The discussion that follows assumes that the patient's illness is severe enough
to require hospital admission or to pursue an etiologic diagnosis since specific etiologic
diagnosis is usually not sought in otherwise healthy patients with mild respiratory tract infections
who are treated symptomatically as outpatients. (See "Respiratory syncytial virus infection:
Clinical features and diagnosis", section on 'Diagnosis'.)

Indications for hospitalization in children with bronchiolitis are discussed separately.

(See "Bronchiolitis in infants and children: Treatment; outcome; and prevention", section on
'Indications for hospitalization'.)

Outpatient treatment for patients with upper respiratory tract infections, bronchiolitis, or
pneumonia who do not have a specific microbiologic diagnosis are discussed separately.
(See "Bronchiolitis in infants and children: Treatment; outcome; and
prevention" and "Community-acquired pneumonia in children: Outpatient treatment", section on
'Empiric therapy' and "The common cold in children: Treatment and prevention", section on
'Treatment'.)
Therapy for RSV infection of the lower respiratory tract is primarily supportive. Inhaled
bronchodilators are not routinely recommended for infants and young children with bronchiolitis,
but a one-time trial may be warranted for those with severe disease (eg, nasal flaring;
retractions; grunting; respiratory rate >70 breaths per minute; dyspnea; or cyanosis).
(See "Bronchiolitis in infants and children: Treatment; outcome; and prevention", section on
'Inhaled bronchodilators'.)

Antiviral agents are available, but their use is not indicated in most patients. More aggressive
therapy, including immunotherapy, or antiviral and immunotherapy with or without
corticosteroids may be warranted for immunocompromised patients, as described below.
(See 'Ribavirin' below and 'Passive immunotherapy' below and 'Combination therapy' below.)

SUPPORTIVE CARE — Supportive care for children with RSV lower respiratory tract infection
(LRTI) may include hospitalization and fluid and respiratory support. The supportive care and
inpatient treatment for bronchiolitis and pneumonia are discussed in detail separately. Important
aspects of care and those specific to children with RSV will be summarized below.
(See "Bronchiolitis in infants and children: Treatment; outcome; and prevention", section on
'Supportive care' and "Pneumonia in children: Inpatient treatment", section on 'Supportive care'.)

Respiratory support — Infants with RSV bronchiolitis and pneumonia frequently have arterial
oxygen saturations of ≤90 percent. Infants whose oxygen saturation is consistently ≤90 percent
should be treated with supplemental oxygen. (See "Continuous oxygen delivery systems for
infants, children, and adults".)

Mechanical ventilation may be required in patients with severe respiratory

symptoms and/or apnea due to RSV. The frequency of mechanical ventilation varies according
to age and underlying health status from approximately 5 percent in infants hospitalized with
RSV to up to 50 percent of adults with leukemia and myelosuppression [2-6].

PHARMACOTHERAPY

Bronchodilators — We do not routinely suggest inhaled bronchodilators for children with RSV
bronchiolitis. Meta-analyses of randomized trials and systematic reviews suggest that
bronchodilators may provide modest short-term clinical improvement, but do not affect overall
outcome, may have adverse effects, and increase the cost of care [7-10]. (See "Bronchiolitis in
infants and children: Treatment; outcome; and prevention", section on 'Inhaled bronchodilators'.)

Corticosteroids — We recommend against the use of corticosteroids in infants and young

children (<24 months) with RSV bronchiolitis or pneumonia. In older children and adults,
corticosteroids may be beneficial in the management of RSV-associated bronchial reactivity,
particularly in those with asthma, in whom RSV reinfection may have triggered an exacerbation.
(See "Acute asthma exacerbations in children: Emergency department management".)

Corticosteroids have the potential to decrease bronchiolar swelling and airway obstruction
through their antiinflammatory effects. However, in randomized trials [11,12], meta-analyses
[13], and systematic reviews [14,15], they have not been shown to be beneficial for the
treatment of bronchiolitis. Data are limited on the use of corticosteroids in patients with
bronchiolitis who require mechanical ventilation.

The use of corticosteroids in the treatment of bronchiolitis in children is discussed in detail

separately. (See "Bronchiolitis in infants and children: Treatment; outcome; and prevention",
section on 'Systemic glucocorticoids'.)
Ongoing studies are evaluating the value of corticosteroid therapy in combination with passively
administered antiviral immunoglobulin, particularly in immune-compromised patients, as
discussed below. (See'Combination therapy' below.)

Bronchodilators plus corticosteroids — Combination therapy with bronchodilators and

corticosteroids in infants with bronchiolitis is discussed separately. (See "Bronchiolitis in infants
and children: Treatment; outcome; and prevention", section on 'Bronchodilators plus
glucocorticoids'.)

Hypertonic saline — The use of hypertonic saline in the treatment of RSV bronchiolitis in
children is discussed separately. (See "Bronchiolitis in infants and children: Treatment;
outcome; and prevention", section on 'Nebulized hypertonic saline'.)

Ribavirin — Ribavirin is a nucleoside analog with good in vitro activity against RSV. Ribavirin is
approved by the US Food and Drug Administration (FDA) for the treatment of RSV infection.

In children — The routine use of nebulized ribavirin in infants and children with RSV lower
respiratory tract infection (LRTI) is not recommended. The efficacy of ribavirin in this population
has not been clearly proven [16,17]. In addition, ribavirin is expensive and must be given early
in the course to be effective, and there are concerns regarding occupational exposure [16].
(See 'Adverse effects' below.)

Randomized controlled trials comparing ribavirin with placebo in children with RSV LRTI have
yielded mixed results. Some studies have demonstrated decreased severity of illness,
decreased duration of mechanical ventilation, oxygen therapy and hospital stay, and decreased
viral shedding [18-21], whereas other studies have not demonstrated these benefits [22-24]. A
2004 systematic review of randomized trials comparing ribavirin with placebo in infants and
children with RSV infection and LRTI found that trials of ribavirin lack sufficient power to provide
reliable estimates of the effects [16].

The American Academy of Pediatrics (AAP) recommends against the routine use
of ribavirin [25]. Ribavirin should be reserved for immunosuppressed patients with severe RSV
infection. Consultation with an expert in infectious diseases is recommended before its use.

In adults — Although the routine use of ribavirin is not recommended for infants and children
with RSV LRTI, ribavirin may be beneficial for certain adults. Early use of inhaled ribavirin has
been shown to reduce morbidity and mortality in adult hematopoietic cell transplant recipients
who develop RSV infections [26,27]. In small case series, oral ribavirin has been used to
successfully treat RSV upper and lower respiratory tract disease in adult hematopoietic cell
transplant recipients [28,29]. The efficacy of ribavirin for patients with solid-organ transplants is
unknown [30,31].

Contraindications — Ribavirin is considered to be contraindicated in pregnant women, and a

negative pregnancy test should precede its use in women of child-bearing age. (See 'Pregnant
women' below.)

The prescribing information for oral ribavirin recommends that ribavirin be avoided in men
whose partners are pregnant [32]. Given the long half-life of ribavirin, it is also recommended
that women who receive ribavirin and the female partners of men who receive ribavirin avoid
pregnancy for six months after completion of treatment.

Adverse effects — Adverse effects related to occupational exposure to ribavirin have not been
reported. However, the National Institute of Occupational Safety and Health has published
recommendations to reduce the ambient air concentrations of ribavirin and limit occupational
exposure to hospital personnel [33].

Passive immunotherapy — In a 2006 systematic review, neither intravenous immunoglobulin

with a high neutralizing activity against RSV (RSVIG) nor monoclonal antibody proved beneficial
in the treatment of RSV in hospitalized infants and young children [34]. RSVIG is no longer
available.

A pilot study of treatment with RSVIG demonstrated decreased viral shedding and improvement
in oxygenation in children with RSV LRTI [35]. However, subsequent randomized studies found
no benefit in reducing hospital stay, intensive care unit stay, mechanical ventilation, or the need
for supplemental oxygen [36,37]. Similarly, a study using an RSV-specific humanized
monoclonal antibody (palivizumab) also found no benefit when used as therapy (rather than
prophylaxis, which is discussed separately) [38]. (See "Respiratory syncytial virus infection:
Prevention", section on 'Palivizumab'.)

Additional monoclonal antibodies against RSV are being studied, but have no current clinical
applications [39-41].

Combination therapy

Ribavirin and immunotherapy — Combined antiviral therapy and immunotherapy may be

warranted in severely ill immunocompromised patients with RSV LRTI [42].

Adult hematopoietic cell transplant patients with RSV pneumonia have a high risk of mortality
(approximately 70 percent) [43]. In these patients, uncontrolled studies suggest that
combination therapy withribavirin and intravenous immunoglobulin is associated with improved
survival [44-48]. Additional studies in RSV-infected lung transplant recipients have suggested
that combined ribavirin (nebulized or intravenous) with intravenous
immunoglobulin and/or corticosteroids can reduce mortality, length of mechanical ventilation,
and incidence of bronchiolitis obliterans [49].

Although combined ribavirin and intravenous immunoglobulin has not been supported by a
randomized trial, this expensive treatment is now sometimes used in selected patients.

Similarly, the combination of intravenous immunoglobulin and palivizumab is sometimes used in

severely ill immunocompromised patients but has not been well studied.

Ribavirin and corticosteroids — We suggest ribavirin in combination with passive

immunotherapy and/or corticosteroids for immune-compromised adults with severe RSV LRTI.
Combined treatment with intravenous ribavirin and oral corticosteroids in an uncontrolled study
of 18 adult lung transplant recipients was well tolerated and cleared RSV infection by
immunofluorescent antibody testing. There was no mortality, and only one patient developed
bronchiolitis obliterans [50].

PREGNANT WOMEN — The management of pregnant women with RSV is similar to that for
other adults (see 'Overview' above), except that ribavirin is avoided because studies in rodents
(rats, rabbits, hamsters) demonstrated teratogenicity and/or embryolethality [51]. The risk in
human pregnancy is uncertain due to the small number of reported exposures, but preliminary
findings from a ribavirin pregnancy registry have not suggested human teratogenicity [52]. Birth
defects occurred in 3 of 49 live births with direct maternal exposures and 3 of 69 live births
following indirect exposure via the male sexual partner, with no consistent pattern of
abnormality.
 INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials,
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th th
language, at the 5 to 6 grade reading level, and they answer the four or five key questions a
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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
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at the 10 to 12 grade reading level and are best for patients who want in-depth information
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Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)

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

SUMMARY AND RECOMMENDATIONS

●Therapy for respiratory syncytial virus (RSV) infection of the lower respiratory tract is
primarily supportive. Supportive care may include hospitalization and fluid and respiratory
support. (See 'Supportive care' above.)
●We suggest that inhaled bronchodilators not be used routinely for children with RSV
bronchiolitis (Grade 2B). (See 'Bronchodilators' above.)
●We recommend not using corticosteroids in infants and young children (<24 months) with
RSV bronchiolitis or pneumonia (Grade 1A). However, corticosteroids may be beneficial in
the management of lower airway obstruction in older children and adults.
(See 'Corticosteroids' above.)
●We recommend not using ribavirin routinely in the management of infants and children
with RSV lower respiratory tract infection (LRTI) (Grade 1B). (See 'Ribavirin' above.)
●We suggest ribavirin in combination with passive immunotherapy and/or corticosteroids
for immune-compromised adults with severe RSV LRTI (Grade 2C). (See 'Ribavirin' above
and 'Combination therapy' above.)
●Neither intravenous immunoglobulin with a high neutralizing activity against RSV nor
monoclonal antibody has as yet proven beneficial in the treatment of RSV in hospitalized
infants and young children. (See 'Passive immunotherapy' above.)
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