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Respiratory syncytial virus infection: Treatment

Respiratory syncytial virus infection: Treatment
Authors:
Frederick E Barr, MD, MBA
Barney S Graham, MD, PhD
Section Editor:
Morven S Edwards, MD
Deputy Editor:
Mary M Torchia, MD
Literature review current through: Jun 2022. | This topic last updated: Apr 22, 2022.

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 RSV in infants, children, and adults will be discussed here. The discussion 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'.)

The epidemiology, microbiology, clinical manifestations, diagnosis, and prevention of RSV infection and outpatient treatment for patients with upper respiratory tract infections, bronchiolitis, and community-acquired pneumonia who do not have a specific microbiologic diagnosis are discussed separately.

(See "Respiratory syncytial virus infection: Clinical features and diagnosis" and "Respiratory syncytial virus infection: Prevention in infants and children".)

(See "The common cold in children: Management and prevention" and "The common cold in adults: Treatment and prevention".)

(See "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on 'Nonsevere bronchiolitis'.)

(See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Empiric therapy' and "Treatment of community-acquired pneumonia in adults in the outpatient setting", section on 'Empiric antibiotic treatment'.)

SUPPORTIVE CARE — Therapy for RSV infection of the lower respiratory tract is primarily supportive [2,3]. Supportive care for patients with RSV lower respiratory tract infection includes frequent monitoring of clinical status and provision of and fluid and respiratory support as necessary. The supportive care and inpatient treatment for bronchiolitis and pneumonia are discussed in detail separately. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on 'Severe bronchiolitis' and "Pneumonia in children: Inpatient treatment", section on 'Supportive care'.)

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 [4-8].

INDIVIDUALIZED MANAGEMENT

RSV bronchiolitis

General management – Children with RSV bronchiolitis are treated in the same manner as children with bronchiolitis caused by other pathogens. Supportive care is the mainstay of management. Inhaled bronchodilators, inhaled hypertonic saline, and inhaled and systemic glucocorticoids are not routinely recommended. Treatment of bronchiolitis, including RSV bronchiolitis, is discussed in detail separately. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)

Unproven therapies

Ribavirin – Ribavirin is a nucleoside analog with good in vitro activity against RSV. Although ribavirin is available for the treatment of RSV infection, it is not routinely recommended for infants and children with RSV lower respiratory tract infection (LRTI). The efficacy has not been clearly proven [9,10]. In addition, ribavirin is expensive and must be given early in the course to be effective, and there are concerns regarding occupational exposure [9]. (See 'Ribavirin' 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 [11-14], whereas other studies have not demonstrated these benefits [15-17]. 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 [9].

The American Academy of Pediatrics recommends against the routine use of ribavirin [18]. Ribavirin should be reserved for immunosuppressed patients with severe RSV infection. Consultation with an expert in infectious diseases is recommended before its use.

RSV-IVIG – Intravenous immune globulin with a high neutralizing activity against RSV (RSV-IVIG) is no longer available. Although a pilot study suggested promise, in subsequent randomized trials in children with RSV LRTI [19], no benefit in reducing hospital stay, intensive care unit stay, mechanical ventilation, or the need for supplemental oxygen was detected [20-22].

Palivizumab – Palivizumab is an RSV-specific humanized monoclonal antibody. In randomized trials in children with RSV bronchiolitis, no treatment benefit of palivizumab has been detected [23,24].

Prophylactic use of palivizumab is discussed separately. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Palivizumab immunoprophylaxis'.)

Other monoclonal antibodies – Additional monoclonal antibodies against RSV are being studied but remain investigational [25].

RSV-associated bronchial reactivity — Glucocorticoids and bronchodilators may be beneficial in the management of RSV-associated bronchial reactivity in older children and adults, particularly those with asthma, in whom RSV-reinfection may have triggered an exacerbation. (See "Treatment of recurrent virus-induced wheezing in young children" and "Acute asthma exacerbations in children younger than 12 years: Inpatient management", section on 'Elements of treatment' and "Acute exacerbations of asthma in adults: Emergency department and inpatient management".)

Immunocompromised patients — Decisions regarding treatment of RSV infection in immunocompromised patients should be individualized. Treatment of RSV infection in immune-compromised patients has not been well studied and the optimal treatment is uncertain [26,27].

Interventions that have been associated with benefit (eg, reduced rates of progression from upper to LRTI, decreased mortality) in observational studies include single agent or combination therapy with ribavirin, intravenous immune globulin, palivizumab, and/or glucocorticoids [26,27]. Although combination therapy with intravenous immune globulin and ribavirin or palivizumab has not been supported by a randomized trial, these combinations are sometimes used in severely ill immunocompromised patients.

Special populations of immunocompromised patients

Hematopoietic cell transplant recipients — Factors to be considered in the choice of therapy for hematopoietic cell transplant (HCT) recipients with RSV infection include type of RSV infection (eg, upper or lower respiratory tract infection), risk of progression to LRTI (eg, absolute lymphocyte count, absolute neutrophil count), and severity of respiratory compromise [28].

Adult HCT patients with RSV pneumonia have a high risk of mortality (approximately 70 percent) [29]. In observational studies in adult HCT recipients with RSV infection, early use of nebulized ribavirin has been associated with reduced morbidity and mortality [30-32].

Oral ribavirin may be a reasonable alternative to nebulized ribavirin. In small case series of HCT recipients with RSV upper and LRTI, oral ribavirin was also associated with reduced morbidity and mortality [33-35]. In a review of 124 HCT recipients with RSV infections, the rate of progression to LRTI (approximately 27 percent) and 30-day mortality (approximately 10 percent) were similar among those treated with oral (n = 54) and nebulized (n = 70) ribavirin [36]. Only 18 of the included patients were classified as high risk, and the findings may not be generalizable to this population [37].

Uncontrolled trials suggest that combination therapy with nebulized ribavirin and intravenous immune globulin is associated with improved survival in adult HCT recipients with RSV infection [28,38-42].

Lung transplant recipients — The management of RSV in lung transplant recipients is discussed separately. (See "Viral infections following lung transplantation", section on 'Respiratory syncytial virus'.)

Other solid organ transplant recipients — The management of RSV in patients with other types of solid organ transplant is individualized. Oral or nebulized ribavirin is often administered to heart-lung transplant recipients with upper or LRTI and may be warranted for non-lung solid organ transplant recipients with LRTI [43,44].

PHARMACOTHERAPEUTIC AGENTS

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

Potential indications – Nebulized or oral ribavirin, alone or in combination with other interventions, may be warranted for the treatment of documented RSV infection in immunocompromised patients. (See 'Immunocompromised patients' above and 'Special populations of immunocompromised patients' above.)

Ribavirin is not routinely recommended for the treatment of RSV bronchiolitis in infants and children. (See 'RSV bronchiolitis' above.)

Contraindications and precautionsRibavirin is contraindicated in pregnant females, and a negative pregnancy test should precede its use in women of child-bearing age.

Studies in rodents (rats, rabbits, hamsters) demonstrated teratogenicity and/or embryolethality [45]. 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 [46]. Congenital anomalies 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.

The prescribing information for oral ribavirin recommends that ribavirin be avoided in males whose partners are pregnant [47]. Given the long half-life of ribavirin, it is also recommended that female patients who receive ribavirin avoid pregnancy for nine months after completion of treatment and that the female partners of males who receive ribavirin avoid pregnancy for six months after completion of treatment.

Ribavirin has been associated with bronchoconstriction and should be used in caution in patients with asthma or chronic obstructive pulmonary disease [28].

Adverse effects – Adverse effects of ribavirin include hemolytic anemia, leukopenia, cough, dyspnea, bronchospasm, deterioration in pulmonary function, rash, conjunctival irritation, and neuropsychologic symptoms [26,28,43,48].

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 [49].

Immune globulin — Intravenous immune globulin (IVIG) alone or in combination with other agents (eg, ribavirin, palivizumab) has been tried in the treatment of RSV infection. Although it is no longer available, IVIG with high neutralizing activity against RSV (RSV-IVIG) was shown to prevent RSV replication in lung tissues, reduce viral loads in pulmonary tissues, and prevent subsequent development of illness in immunocompetent and immunocompromised animal models [50,51].

IVIG may be warranted for the treatment of documented RSV infection in immunocompromised patients. (See 'Immunocompromised patients' above and 'Special populations of immunocompromised patients' above.)

The clinical use and adverse effects of IVIG are discussed separately. (See "Overview of intravenous immune globulin (IVIG) therapy" and "Intravenous immune globulin: Adverse effects".)

Palivizumab — Palivizumab is an RSV-specific humanized monoclonal antibody. The typical intravenous dose (15 mg/kg) has a serum half-life of approximately 20 days in adult hematopoietic cell transplant (HCT) recipients without RSV and 11 days in HCT recipients with RSV infection [52].

Whether specific populations of immunocompromised patients benefit from palivizumab therapy for RSV infection is uncertain. It has not been evaluated in randomized trials. In observational studies, palivizumab has not been definitively associated with reduced severity of RSV infection or mortality, although it appears to be well tolerated [52-54]. Adverse reactions to palivizumab include fever, rash, and antibody development.

Prophylactic use of palivizumab is discussed separately. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Palivizumab immunoprophylaxis'.)

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 5th to 6th 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 10th to 12th 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.)

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

SUMMARY AND RECOMMENDATIONS

Supportive care – Therapy for respiratory syncytial virus (RSV) infection of the lower respiratory tract is primarily supportive. Supportive care includes frequent monitoring of clinical status and provision of fluid and respiratory support as necessary. (See 'Supportive care' above.)

Children with RSV bronchiolitis are treated in the same manner as children with bronchiolitis caused by other pathogens. Supportive care is the mainstay of management. Pharmacotherapy is not routinely recommended. Treatment of bronchiolitis is discussed separately. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention".)

Glucocorticoids and bronchodilators may be beneficial in the management of RSV-associated bronchial reactivity in older children and adults. (See 'RSV-associated bronchial reactivity' above.)

Treatment of immunocompromised patients – Decisions regarding treatment of RSV infection in immunocompromised patients should be individualized. The optimal treatment is uncertain. Interventions that have been associated with reduced rates of progression from upper to lower respiratory tract infection or decreased mortality in observational studies include single agent or combination therapy with ribavirin, intravenous immune globulin, palivizumab, and/or glucocorticoids. (See 'Immunocompromised patients' above and 'Special populations of immunocompromised patients' above.)

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