Respiratory syncytial virus

Shmuel Shoham, M.D.

MICROBIOLOGY

Negative-sense, single-strand, enveloped RNA virus.
- There are two subtypes (A and B). The severity may be similar between the two viruses.
The scientific name is human orthopneumovirus.
- The synonym is human respiratory syncytial virus (hRSV), sometimes shortened to just RSV.
- Member of the Pneumoviridae family and Orthopneumovirus genus.
RSV fusion protein facilitates the fusion of the viral envelope with the host cell membrane. This protein is a target for vaccines and anti-viral agents.
In this section, we will refer to the virus that infects humans as RSV (although human orthopneumovirus is the International Committee on Taxonomy of Viruses preferred term).
Transmission:
- There are no animal reservoirs for this virus.
- Spread via nasal or oral secretions, either directly via large droplets (and probably aerosolized particles) or indirectly through contact with contaminated hands and environmental surfaces (e.g., cribs, toys, doorknobs, tabletops)

CLINICAL

Major respiratory tract pathogen of humans.
- Almost all children in the U.S. will have had RSV infection by age 2.
- Reinfection can occur throughout life.
  - Healthcare workers and those working with children are at higher risk for RSV reinfections.
- The incubation period is 2-8 days.
- Infants/young children:
  - RSV is the leading cause of pneumonia in children under 5.
  - Bronchiolitis:
    - Infection of the bronchioles typically occurs in children aged 2 or younger; clinical manifestations include shortness of breath, wheezing, and potentially hypoxemia.
  - Risks: prematurity; low birth weight; younger age; chromosomal abnormalities (e.g., Down syndrome); congenital heart, lung and immune conditions; smoking in the household; crowding; and lower socioeconomic status.
  - RSV infection can lead to exacerbation of existing asthma and the development of reactive airways as a sequela of infection.
  - There is an association between RSV and the development of asthma and chronic lung disease later in life.
- Older adults:
  - One of the top causes of influenza-like illness in this population.
  - 60,000–160,000 hospitalizations and 6,000–10,000 deaths/year in U.S. adults > 65 years old. Highest rates for hospitalization for age ≥75 years.
  - Risks: chronic lung and heart disease (e.g., COPD and CHF), neuromuscular disease, chronic kidney and liver disease, diabetes mellitus, hematologic disorders, cerebrovascular disease, frailty, immunosuppression, residents of long-term facilities
  - May cause exacerbation of COPD and CHF.
  - RSV infection often leads to unnecessary treatment with antibacterial drugs.
Disease activity:
- The typical season in the U.S. is from October to May, with a peak in January and February.
- Human activity can impact seasonality, and RSV activity may vary by region.
  - During the SARS-CoV-2 pandemic, RSV did not follow seasonal trends.
    - Following an absence in the remainder of 2020 for nearly a year (likely due to social mitigation and competing SARS-CoV-2 infections), there were increased cases in the summer of 2021 and a severe spike in autumn 2022 among young children and the elderly.
- Nosocomial: may occur with spread, especially in pediatric wards, nursing homes, and transplant/oncology wards.
Spectrum of disease:
- Pediatrics: a significant cause of infection
  - Most commonly, "colds," otitis, croup, bronchitis, bronchiolitis, community-acquired pneumonia, and asthma exacerbations or precipitant thereof.
    - RSV is one of many causes of viral URI in children.
  - In young children, 25-40% of cases have bronchiolitis and/or pneumonia.
  - Very young children experiencing RSV for the first time are at the highest risk for severe disease.
    - About 1-2% of children < 6 months of age may be sick enough to require hospitalization.
- Adult:
  - URI symptoms are common (e.g., nasal congestion, cough, sputum production).
    - It may be indistinguishable from influenza or COVID.
    - Complications: pneumonia, chronic lung disease exacerbation, heart failure, myocardial infarction, bacterial superinfection, need for hospitalization, mechanical ventilation and mortality.
    - Risk groups for complication: age ≥65, cardiac disease, pulmonary disease, immune compromise (especially lymphopenia)
- Immunosuppressed:
  - Hematological malignancies and hematopoietic stem cell transplant: a major problem is lower respiratory tract infection, which is associated with significant morbidity, need for ICU stay and mortality (~25% or higher).
    - Risks for progression from upper to lower respiratory tract infection include absolute neutrophil count ≤ 500/ mm³, absolute lymphocyte count ≤ 100/ mm³, older age, myeloablative conditioning regimen, graft vs. host disease, infection before or around the time of engraftment, smoking history and possibly steroids.
    - The mortality risk is correlated with the intensity of immunosuppression, especially neutropenia and lymphopenia and with radiographic severity of the disease.
  - Solid organ transplant: especially lung transplant recipients, where mortality attributable to lower respiratory tract disease is ~10-20%.
    - Worse outcomes are also seen in pediatric transplant recipients and in those with preexisting lung disease, a recent transplant, recent rejection, and multivisceral transplant.
    - A possible link between RSV infection and the development of long-term lung damage (bronchiolitis obliterans syndrome) in lung transplant recipients.
Diagnosis:
- Nucleic amplification (RT-PCR): the most sensitive method and especially important for evaluating older children and adults who tend to have lower viral titers in respiratory secretions.
  - Most often, it is now part of a multiplex respiratory panel.
- The antigen test is most effective for infants and young children (sensitivity at 80-90% range).
  - It is less sensitive in older children and adults as the viral load is lower.
- Tissue culture: Largely supplanted by the above tests, so less commonly used for diagnosis.

SITES OF INFECTION

Upper respiratory tract: may occur +/- sinusitis, otitis media
- Bronchi: laryngotracheobronchitis (croup), bronchitis, bronchiolitis (especially in infants), asthma.
Lung: pneumonia: radiographic changes are unilateral in ~80% of cases, most commonly consolidations and/or ground-glass opacities.
CNS: meningitis, encephalitis (rare).
Cardiac: myocarditis (rare).
Derm: exanthem (rare).

TREATMENT

Antiviral therapy

Supportive care is the cornerstone of therapy. This is the only therapy required for most children and adults with RSV infection.
Pediatrics
- Ribavirin and IVIG are used for the sickest.
- Prophylaxis with palivizumab (RSV‐specific humanized monoclonal antibody): see below
  - The drug has failed in trials for treatment.
Immunocompromised (e.g., hematological malignancies, hematopoietic stem cell and solid organ transplant recipients)
- Ribavirin is available orally and in IV form in Europe.
  - NOTE: Efficacy in adults with HSCT is controversial. It seems to be most helpful in preventing the progression of upper to lower respiratory tract disease. In lung transplant recipients, it may reduce subsequent long-term lung dysfunction, but this, too, is controversial with limited, mixed data.
  - Aerosolized: various approaches to dosing.
    - One example is a 6-gram dose continuously over 6 hours.
    - Must be given with care to avoid environmental and healthcare worker exposure to the drug.
    - Costly (~$30,000/day).
    - Many centers do not use it for the above reasons.
  - Oral:
    - Dosing (weight-based):
      - ≥75 kg: 800 mg PO twice daily
      - < 75 kg: 600 mg PO twice daily
      - Adjust for renal insufficiency, if present.
      - Another dosing scheme: 15-20 mg/kg PO in three divided doses
    - Duration: 7-10 days is increasingly used
    - Outcomes: similar to aerosolized, but much less expensive and cumbersome.
  - IV: This may be used if the patient cannot tolerate the oral formulation.
- Combination therapy:
  - Systemic ribavirinAND IVIG (or high RSV Ab titer IVIG): used for allogeneic hematopoietic stem cell transplant patients with lower respiratory tract infection or are at high risk for progression to lower tract disease.
  - Consider monoclonal antibody specific for the RSV-F protein (palivizumab at 15 mg/kg) for allogeneic hematopoietic stem cell transplant recipients < 2 years old with lower respiratory tract infection or at high risk for progression to lower tract disease.
  - Consider adjunctive corticosteroids in lung transplant patients with RSV.
Experimental:
- GS-508[17]: blocks viral-envelope fusion with the host-cell membrane: Treatment with oral GS-5806 reduced the viral load and clinical disease severity in healthy adults experimentally infected with RSV.
- EDP-938, a nonfusion replication inhibitor of RSV, modulates the viral nucleoprotein with promising Phase 2 data[9].

Prevention

Infection control: hand washing, gown, gloves, surface decontamination.
Delaying hematopoietic stem cell transplant in patients with RSV upper respiratory tract infection reduces the risk of progression to RSV pneumonia.
Monoclonal antibodies (mAb)
- Nirsevimab:
  - Long-acting anti-RSV prefusion protein mAb.
    - Administered as an intramuscular injection shortly before or during the RSV season.
  - First RSV season of an infant’s life:
    - All infants < 8 months of age: 1 dose.
      - The dose for weight
        < 5 kg: 50 mg
        ≥5 kg: 100 mg
  - Second RSV season: Infants and children 8-19 months of age and at risk for severe RSV (e.g.chronic lung or heart disease, severe immunocompromise, neuromuscular disease, American Indian or Alaska Native children):
    - 200 mg (given as two 100 mg injections given simultaneously at different injection sites) before the start of RSV season.
  - Children undergoing cardiac surgery with cardiopulmonary bypass should receive an additional dose once they are stable post-surgery to ensure drug levels are high enough.
- Palivizumab (humanized monoclonal antibody) has been recommended as passive immunoprophylaxis during RSV season for high-risk eligible infants (see below). However, with the development of nirsevimab, which requires fewer doses and is more cost-effective, it is unclear how palivizumab will continue to be utilized.
  - Timing of administration: Monthly doses (up to a maximum of 5) during RSV season.
    - Because RSV activity can vary by region, the American Academy of Pediatrics (AAP) currently supports using palivizumab in eligible infants in any region experiencing rates of RSV activity at any time, similar to a typical fall-winter season.
  - Patient types
    - In the first year of life for infants born before 29 weeks gestation.
    - In the first year of life for preterm infants with chronic lung disease of prematurity (birth at < 32 weeks gestation and a requirement for >21% oxygen for at least 28 days). This may continue for longer depending on ongoing respiratory support needs.
    - In the first year of life, certain infants with hemodynamically significant heart disease, pulmonary abnormalities or neuromuscular disease impair the ability to clear secretions from the upper airways.
    - Children younger than 24 months will be profoundly immunocompromised during the RSV season.
Vaccines: see the RSV vaccines module for more details.
- Three vaccines are now approved. None are with a live virus
  - RSVPreF3 (Arexvy, GSK): single dose (0.5 mL)
  - RSVpreF (Abrysvo, Pfizer): single dose (0.5 mL)
  - mRNA-1345 (Mresvia, Moderna): single dose (0.5 mL)
- Vaccine recommendations/approvals for elderly and younger high-risk people:
  - CDC: All adults ≥ 75 years of age
  - CDC: Adults 60-74 years of age who are at increased risk of severe RSV disease (e.g., chronic heart or lung disease, immunocompromised, severe diabetes, severe obesity, nursing home or long-term care facility residents)
  - The FDA also approved Abrysvo (Pfizer) for preventing RSV lower respiratory tract disease in individuals aged 18 through 59 who are at increased risk for such complications.
- Pregnancy: For people at 32 through 36 weeks gestation, given just before or during RSV season to prevent RSV lower respiratory tract infection in infants.
  - RSVpreF (Abrysvo, Pfizer): single dose (0.5 mL):
    - Reduces risk of RSV hospitalization for infants by 57% in the first 6 months after birth.
    - Only Abrysvo has this indication.

Selected Drug Comments

Drug	Recommendation
Ribavirin	FDA-approved for inhalation use in pediatrics; many authorities are not impressed. For immune-compromised adults, ribavirin has been used as oral administration 10–30 mg/kg body weight in 3 divided doses/day with good results. (Aerosolization in adults is logistically challenging and very expensive.) IV ribavirin is produced but is not commercially available in the U.S.
Nirsevimab	FDA approved for the prevention of RSV in all infants < 8 months of age for the first RSV season of their life and for infants and children between 8-19 months who are entering the second RSV season of their life and have conditions that put them at high risk for severe RSV disease (e.g., chronic heart, lung, neurological diseases, immune compromise)
Palivizumab	Only FDA-approved as a preventative measure in high-risk infants (e.g., bronchopulmonary dysplasia, premature birth, and hemodynamically significant congenital heart disease). Some clinicians do not believe the drug is compelling, given the cost and evidence for efficacy. Recent literature review suggests efficacy only for those born < 33 weeks with lung or cardiac conditions[19].
RSVPreF3 (GSK)	1-dose (0.5 mL) vaccination for adults aged ≥60 to prevent RSV lower respiratory tract disease
RSVpreF (Pfizer)	1-dose (0.5 mL) vaccination for adults aged ≥60 to prevent RSV lower respiratory tract disease. 1-dose (0.5 mL) vaccination during pregnancy at 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection in infants. Given just before or during the RSV season.
mRNA-1345 (Moderna)	1-dose (0.5 mL) vaccination for adults aged ≥60 to prevent RSV lower respiratory tract disease.

Basis for recommendation

Melgar M, Britton A, Roper LE, et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(29):793-801. [PMID:37471262]
Comment: ACIP recommendations on the RSV vaccines for adults.
Jones JM, Fleming-Dutra KE, Prill MM, et al. Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(34):920-925. [PMID:37616235]
Comment: Recommendations of the Advisory Committee on Immunization Practices (ACIP) of the CDC regarding the use of nirsevimab for the prevention of RSV in infants and children
Manuel O, Estabrook M, American Society of Transplantation Infectious Diseases Community of Practice. RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9):e13511. [PMID:30817023]
Comment: Practice guidelines for prevention and treatment of RSV in solid organ transplant recipients.
Nam HH, Ison MG. Respiratory syncytial virus infection in adults. BMJ. 2019;366:l5021. [PMID:31506273]
Comment: Leading respiratory virus infection investigator highlights the increasingly diagnosed infection in adults with the advent of widely used multiplex panels. Treatment is focused on those with severe disease and includes ribavirin and IVIG.
American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-20. [PMID:25070315]
Comment: This document provides guidelines for using RSV prophylaxis in infants at risk for serious respiratory illness due to this virus. A revision to this guideline includes: Otherwise, healthy infants with a gestational age of 29 weeks or more should not receive palivizumab to prevent respiratory syncytial virus infections. Infants under one year of age with hemodynamically significant heart disease or chronic lung disease of prematurity should be treated with palivizumab, up to a maximum of 5 monthly doses, during the respiratory syncytial virus season. Risk factors for severe disease include age under 12 weeks, prematurity, underlying cardiopulmonary disease, and immunodeficiency. This document was not yet updated in 2023 with new products (vaccines, mab).
Hirsch HH, Martino R, Ward KN, et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis. 2013;56(2):258-66. [PMID:23024295]
Comment: Evidence-based guidelines for the treatment of RSV infections in immunocompromised hematology patients.

References

Perez A, Lively JY, Curns A, et al. Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021. MMWR Morb Mortal Wkly Rep. 2022;71(40):1253-1259. [PMID:36201373]
Comment: Data from CDC demonstrates that during the COVID-19 pandemic, respiratory viruses had lower-than-expected circulation during "respiratory viral seasons" and a spike in RSV cases in the summer of 2021 (which is not the usual RSV season).
Schmoele-Thoma B, Zareba AM, Jiang Q, et al. Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study. N Engl J Med. 2022;386(25):2377-2386. [PMID:35731653]
Comment: Rare viral human challenge study, Phase II study design displaying the safety and efficacy of this vaccine now FDA approved. Compared to current indications, the study was done in younger adults (18-50).
Ahmad A, Eze K, Noulin N, et al. EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge. N Engl J Med. 2022;386(7):655-666. [PMID:35172056]
Comment: Phase 2 study in 115 patients using EDP-938, a nonfusion replication inhibitor of RSV, acts by modulating the viral nucleoprotein. Findings include that compared to placebo, viral load was less, total symptom scores, and mucus weight. The inhibitor appeared to be well tolerated.
Madhi SA, Polack FP, Piedra PA, et al. Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants. N Engl J Med. 2020;383(5):426-439. [PMID:32726529]
Comment: If a vaccine is approved for adults, immunization during pregnancy may well protect infants at their most vulnerable first few months from RSV due to passive transfer of maternal antibodies.
Sheshadri A, Karimipour M, Vakil E, et al. Refinement of estimates of mortality risk using the Radiologic Severity Index in hematologic malignancy patients with respiratory syncytial virus infection. Transpl Infect Dis. 2019;21(4):e13105. [PMID:31081570]
Comment: this study demonstrated that mortality rates for RSV in hematological malignancy patients/stem cell transplant recipients correlate with the severity of the disease as determined by radiographic findings.
Vakil E, Sheshadri A, Faiz SA, et al. Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies. Transpl Infect Dis. 2018;20(6):e12994. [PMID:30195271]
Comment: Studies show that the intensity of immunosuppression (especially neutropenia and lymphopenia) predicts mortality in RSV lower respiratory tract infection in patients with hematological malignancy and stem cell transplantation.
Trang TP, Whalen M, Hilts-Horeczko A, et al. Comparative effectiveness of aerosolized versus oral ribavirin for the treatment of respiratory syncytial virus infections: A single-center retrospective cohort study and review of the literature. Transpl Infect Dis. 2018;20(2):e12844. [PMID:29360277]
Comment: A retrospective study comparing outcomes in immunocompromised patients with RSV infection based on treatment regimen (oral vs. aerosolized ribavirin). Outcomes were similar regardless of the form of drug delivery.
Rating: Important
Paulsen GC, Danziger-Isakov L. Respiratory Viral Infections in Solid Organ and Hematopoietic Stem Cell Transplantation. Clin Chest Med. 2017;38(4):707-726. [PMID:29128020]
Comment: Excellent review of RSV in transplant recipients, including solid organ
Neemann K, Freifeld A. Respiratory Syncytial Virus in Hematopoietic Stem Cell Transplantation and Solid-Organ Transplantation. Curr Infect Dis Rep. 2015;17(7):490. [PMID:26068871]
Comment: Review article focusing upon RSV infection and its treatment in solid organ and hematopoeitic stem cell transplant recipients.
Shah DP, Ghantoji SS, Ariza-Heredia EJ, et al. Immunodeficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections. Blood. 2014;123(21):3263-8. [PMID:24700783]
Comment: This paper describes a classification system useful for stratifying bone marrow transplant patients’ propensity for developing bad outcomes from RSV (low, moderate and high-risk groups).
DeVincenzo JP, Whitley RJ, Mackman RL, et al. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med. 2014;371(8):711-22. [PMID:25140957]
Comment: This paper reported the efficacy of an oral agent (GS-508) that inhibits the fusion of the RSV envelope to human cells. Treatment reduced the viral load and symptoms in patients experimentally infected with RSV.
Rating: Important
Kim YJ, Guthrie KA, Waghmare A, et al. Respiratory syncytial virus in hematopoietic cell transplant recipients: factors determining progression to lower respiratory tract disease. J Infect Dis. 2014;209(8):1195-204. [PMID:24368837]
Comment: An absolute lymphocyte count of >1000 is highly protective against progression from upper to lower respiratory tract disease in HSCT patients with RSV.
Homaira N, Rawlinson W, Snelling TL, et al. Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective. Int J Pediatr. 2014;2014:571609. [PMID:25548575]
Comment: Reviewers found evidence for the recommended use of palivizumab in reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high-risk children, including those with Down syndrome, cystic fibrosis, and hematological malignancy, indicating further research is warranted in these groups.
Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-77. [PMID:23876395]
Comment: This article demonstrates the significant morbidity and mortality associated with RSV infection in adults and particularly in those who are elderly and have chronic lung disease.
Ariza-Heredia EJ, Fishman JE, Cleary T, et al. Clinical and radiological features of respiratory syncytial virus in solid organ transplant recipients: a single-center experience. Transpl Infect Dis. 2012;14(1):64-71. [PMID:22093238]
Comment: Review of 24 cases of RSV infection in adults with solid organ transplants. CT scans showed pulmonary modules and ground-glass opacities; some had small cavities and pleural effusions. Treatment was inhaled or oral ribavirin for 75%. There were no deaths.
Rating: Important
Centers for Disease Control and Prevention (CDC). Respiratory syncytial virus--United States, July 2007-June 2011. MMWR Morb Mortal Wkly Rep. 2011;60(35):1203-6. [PMID:21900874]
Comment: The estimate is 75,000-125,000 hospitalizations/yr in the US for RSV infections in children < 1 year. The total for OPD visits is 1.5 million. Total deaths -- about 250/year.
Walsh EE. Respiratory syncytial virus infection in adults. Semin Respir Crit Care Med. 2011;32(4):423-32. [PMID:21858747]
Comment: Adult RSV infections are common and more consequential in those with COPD and immunosuppression. Diagnosis may be more difficult than in children due to decreased viral shedding. The best method for detection is molecular diagnostics.
Kim SR, Ki CS, Lee NY. Rapid detection and identification of 12 respiratory viruses using a dual priming oligonucleotide system-based multiplex PCR assay. J Virol Methods. 2009;156(1-2):111-6. [PMID:19063921]
Comment: Multiplex PCR assay detects 12 respiratory viruses: parainfluenza 1, 2 & 3, human metapneumovirus, human coronavirus, adenovirus, RSV, influenza A & B and rhinovirus. This "Seeplex" Respiratory Virus Detection assay is FDA-cleared, and initial studies show it is a significant advance.
Georgescu G, Chemaly RF. Palivizumab: where to from here? Expert Opin Biol Ther. 2009;9(1):139-47. [PMID:19063700]
Comment: Review of prophylactic palivizumab (monoclonal antibody) prophylaxis to prevent RSV in high-risk infants and high-risk immunosuppressed patients. This is a review from MD Anderson Hospital that addresses its potential value for treatment, which is extremely expensive and infrequently used.
Hopkins P, McNeil K, Kermeen F, et al. Human metapneumovirus in lung transplant recipients and comparison to respiratory syncytial virus. Am J Respir Crit Care Med. 2008;178(8):876-81. [PMID:18658110]
Comment: Review of viral respiratory infections in patients with lung transplants. Results in 47 patients showed human metapneumovirus in 19 and RSV in 18.
Kurz H, Herbich K, Janata O, et al. Experience with the use of palivizumab together with infection control measures to prevent respiratory syncytial virus outbreaks in neonatal intensive care units. J Hosp Infect. 2008;70(3):246-52. [PMID:18799241]
Comment: Use of palivizumab (15 mg/kg lM) monthly to infants combined with infection control to control outbreaks of RSV.
Khanna N, Widmer AF, Decker M, et al. Respiratory syncytial virus infection in patients with hematological diseases: single-center study and review of the literature. Clin Infect Dis. 2008;46(3):402-12. [PMID:18181739]
Comment: Review of RSV in patients with hematologic diseases. Ten with RSV pneumonia and severe immunodeficiency received ribavirin, IVIG and/or palivizumab -- 5 died, including 4 of 6 who received all three. Authors conclude ribavirin is safe, but efficacy is not established.
Rating: Important
Camargo CA, Ginde AA, Clark S, et al. Viral pathogens in acute exacerbations of chronic obstructive pulmonary disease. Intern Emerg Med. 2008;3(4):355-9. [PMID:18825480]
Comment: PCR testing on nasal secretions showed viral infections in 19 of 76 patients with acute exacerbations of chronic bronchitis. RSV accounted for six or one-third.
Walsh EE, Peterson DR, Falsey AR. Is clinical recognition of respiratory syncytial virus infection in hospitalized elderly and high-risk adults possible? J Infect Dis. 2007;195(7):1046-51. [PMID:17330796]
Comment: A comparison of 144 cases of influenza A and 132 cases of RSV in elderly hospitalized patients showed both groups had high rates of similar findings: URI symptoms, fever and infiltrates on x-ray.
Flynn JD, Akers WS, Jones M, et al. Treatment of respiratory syncytial virus pneumonia in a lung transplant recipient: case report and review of the literature. Pharmacotherapy. 2004;24(7):932-8. [PMID:15303457]
Comment: Lung transplant recipient with RSV pneumonia treated with aerosolized ribavirin and then RSV hyperimmune globulin. The patient survived.
Walsh EE, Peterson DR, Falsey AR. Risk factors for severe respiratory syncytial virus infection in elderly persons. J Infect Dis. 2004;189(2):233-8. [PMID:14722887]
Comment: Prospective study of the risk of RSV infection resulting in hospitalization. The significant risk was: a low neutralizing RSV antibody level and chronic lung disease.
Hashem M, Hall CB. Respiratory syncytial virus in healthy adults: the cost of a cold. J Clin Virol. 2003;27(1):14-21. [PMID:12727524]
Comment: RSV is publicized as an infection of age extremes. The authors review data showing it is an important respiratory pathogen in younger, working adults. Outbreaks are annual and it is highly contagious. Immunity is incomplete and is not durable so repeated infections are common.
van Woensel JB, van Aalderen WM, de Weerd W, et al. Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus. Thorax. 2003;58(5):383-7. [PMID:12728156]
Comment: A controlled trial with dexamethasone (0.15 mg/kg q 6h x 48h) in 37 patients vs. placebo in 45 controls. There was no benefit to steroids.
McCurdy LH, Milstone A, Dummer S. Clinical features and outcomes of paramyxoviral infection in lung transplant recipients treated with ribavirin. J Heart Lung Transplant. 2003;22(7):745-53. [PMID:12873542]
Comment: A controlled trial with 15 lung transplant patients with RSV or parainfluenza infection given aerosolized ribavirin (average of five days). Clinical presentations with RSV or parainfluenza were similar. The outcome show 33% died or failed to return to baseline lung function. Conclusions are limited.
Neuzil KM, Maynard C, Griffin MR, et al. Winter respiratory viruses and health care use: a population-based study in the northwest United States. Clin Infect Dis. 2003;37(2):201-7. [PMID:12856212]
Comment: Study of adult veterans for 1998-2000 with 237,000 person-years of follow-up. Cardiovascular hospitalizations and urgent care visits cycled with influenza and RSV rates. Rates varied between 0.8/1000 (age 18-49) and 10.6/1000 for persons over 65.
Piedra PA, Jewell AM, Cron SG, et al. Correlates of immunity to respiratory syncytial virus (RSV) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies. Vaccine. 2003;21(24):3479-82. [PMID:12850364]
Comment: Analysis of neutralizing antibody levels in 175 pts hospitalized with RSV-associated complications (by culture or serology) showed a protective antibody level. This supports the potential efficacy of an RSV vaccine.
Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289(2):179-86. [PMID:12517228]
Comment: National database w/ projection based on lab surveillance from 1990-1999 for RSV. This virus was found in 17,270 of 107,711 (16%) specimens in patients w/ respiratory tract infections. The total number of deaths attributed to RSV was 11,321 (1%). Of these, 78% were >65 yrs. RSV is a pathogen of age extremes < 5 and >65. At the most significant risk are the "elderly, elderly" persons >85 yrs.
Rating: Important
Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol Rev. 2000;13(3):371-84. [PMID:10885982]
Comment: RATES are CAP 2-5%, nursing homes 5-10%/yr with 10-20% pneumonia & 2-5% death. CLINICAL FEATURES are like influenza - rhinitis, cough, wheezing, and low-grade fever. HIGHEST RISK & mortality - bone marrow tx. DX - best is bronchoscopy, not culture or antigen detection. RX: ribavirin & IVIG for the compromised host. CONTROL: handwashing, gowns & gloves.
Glezen WP, Greenberg SB, Atmar RL, et al. Impact of respiratory virus infections on persons with chronic underlying conditions. JAMA. 2000;283(4):499-505. [PMID:10659876]
Comment: Review of the role of viruses in pulmonary conditions sufficiently severe to cause hospitalization in Houston 1991-95. An analysis of 403 pts showed that 181 (45%) had viral infections, primarily inflluenza, parainfluenza and RSV.
Bowden RA. Respiratory virus infections after marrow transplant: the Fred Hutchinson Cancer Research Center experience. Am J Med. 1997;102(3A):27-30; discussion 42-3. [PMID:10868139]
Comment: IV ribavirin was NOT effective in treating cancer patients with RSV pneumonia.
King JC. Community respiratory viruses in individuals with human immunodeficiency virus infection. Am J Med. 1997;102(3A):19-24; discussion 25-6. [PMID:10868138]
Comment: HIV-infected patients are at increased risk for infection, but severe disease is uncommon.
Garcia R, Raad I, Abi-Said D, et al. Nosocomial respiratory syncytial virus infections: prevention and control in bone marrow transplant patients. Infect Control Hosp Epidemiol. 1997;18(6):412-6. [PMID:9181397]
Comment: The authors emphasize the role of infection control and the possible benefit of aerosolized ribavirin in immunosuppressed adults for preventing the nosocomial spread of RSV.
Harrington RD, Hooton TM, Hackman RC, et al. An outbreak of respiratory syncytial virus in a bone marrow transplant center. J Infect Dis. 1992;165(6):987-93. [PMID:1583345]
Comment: Outbreak involved 31 patients and 35 family members and employees. Of 18 pts with pneumonia, 14 (78%) died. Of 13 with URIs none died.
O'Shea MK, Pipkin C, Cane PA, et al. Respiratory syncytial virus: an important cause of acute respiratory illness among young adults undergoing military training. Influenza Other Respi Viruses. 2007;1(5-6):193-7. [PMID:18846262]
Comment: Surveillance studies in 54 Royal Navy recruits with respiratory symptoms showed adenovirus -- 35%, influenza -- 19% and RSV -- 14%.

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