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respiratory syncytial virus (RSV)

Etiology: - age is the single largest risk factor - pneumonia in infants - lower RSV-specific serum IgG & nasal IgA titers are associated with susceptibility to RSV in the elderly [9] Epidemiology: 1) annual winter outbreaks (October-April) 2) children & adults - 90% of children are infected with RSV during the 1st 2 years of life [8] 3) 22% of patients presenting with flu-like syndrome (vs 32% with culture &/or PCR-documented influenza) 4) annual risks of 3-7% in healthy elderly vs 4-10% in high-risk elderly [2] (twice rate of influenza infection) 5) 10% of elderly hospitalized for acute respiratory symptoms test positive for RSV 6) 1 in 50 deaths among children < 5 years & 1 in 28 deaths in infants < 6 months of age globally. 7) most people with RSV are contagious for 3-8 days [10] - immunocompromised persons & some infants may transmit RSV for up to 4 weeks [10] Pathology: - RSV infection is limited to the respiratory tract [10] - inoculation of RSV occurs in upper respiratory tract epithelial cells - spread of the virus down the respiratory tract occurs through cell-to-cell [10] transfer of the virus along syncytia from upper to lower respiratory tract [10] - RSV viral load is correlated with the severity of disease [9] - neutrophilic inflammation both upper tract & lower respiratory tract - eosinophilic infiltration of the airways may occur - rise in cytotoxic CD8 T-cells is associated with clearance of RSV - clearance of virus from the upper resiratory tract is associated with RSV-neutralizing nasal IgA - RSV replication continues in the airway for about 8 days * Electron micrograph of respiratory syncytial virus [12] Genetics: - negative single-stranded RNA virus - enveloped, spherical virus with a diameter of approximately 150 nm - filamentous forms also noted - RNA-dependent replication cycle of RSV is error prone without a proofreading mechanism allowing single nucleotide polymorphisms (SNPs) & other mutations [9] Clinical manifestations: - mean incubation period is 4-6 days with range of 2-8 days [10] - flu-like syndrome a) fever (generally low grade) b) cough c) myalgias - rhinorrhea is common [3] - tachypnea, intercostal & subcostal retractions [10] - wheezing [10] - cyanosis [10] Laboratory: 1) RSV antigen in tissue 2) RSV serology - rising antibody titer 3) RSV RNA in nasopharyngeal swabs by RT-PCR 4) RSV identified by culture 5) see ARUP consult [2] 6) RSV is a clinical diagnosis that does not necessarily require laboratory testing [10] 7) non-specific testing - complete blood count (CBC - basic metabolic panel - urinalysis - oxygen saturation (SaO2) Complications: - mortality in hospitalized patients roughly equivalent to influenza (10%) [5]; however, patients who died with RSV sicker prior to infection [6] - most common comorbidities were obesity, COPD, congestive heart failure, diabetes mellitus & immunocompromise [6] - 25% of adults >= 50 years hospitalized with RSV infection experienced an acute cardiac event (acute heart failure most common) - 8.5% with no documented underlying cardiovascular disease [15] - long-term care a risk factor for hospitalization due to RSV [18] Management: 1) supportive care, including fluids, antipyretics, & oxygen as needed [16] 2) aerosolized ribavirin is the only FDA-approved treatment 3) palivizumab for prevention - infants born at <32 weeks' gestation who needed >21% oxygen during the first 28 days of life [8] - 5 monthly doses during RSV season in high-risk infants 4) RSV-IgIV (RespiGam) formerly available prior to introduction of palivizumab 5) investigational therapy - a novel oral agent, GS-5806, that interferes with RSV entry by blocking viral-envelope fusion with the host-cell membrane reduces RSV viral load [7] 6) Moderna introduces RSV vaccine 84% effective at preventing lower respiratory tract disease [13] - bivalent prefusion-stabilized F glycoprotein RSV vaccine FDA-approved - vaccines available for older adults Arexvy (GSK) & Abrysvo (Pfizer) [16] - RSV vaccine effective against hospitalization among US adults >= 60 years [17] Notes: - approach to vaccine using structural biology reported [6]

Related

bivalent prefusion-stabilized F glycoprotein RSV vaccine; RSVpreF vaccine (Arexvy, Abrysvo) respiratory syncytial virus immune globulin

General

paramyxoviridae respiratory tract infection

Properties

KINGDOM: virus GENOME-TYPE: RNA SINGLE-STRANDED NEGATIVE-STRAND GENOME-SIZE: 16-20 kB ENVELOPE: PRESENT CAPSID-SYMMETRY: HELICAL

References

  1. Journal Watch 21(24):194, 2001 Zambon MC, Stockton JD, Clewley JP, Fleming DM. Contribution of influenza and respiratory syncytial virus to community cases of influenza-like illness: an observational study. Lancet. 2001 Oct 27;358(9291):1410-6. PMID: 11705487
  2. Journal Watch 25(10):84, 2005 Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005 Apr 28;352(17):1749-59. PMID: 15858184
  3. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
  4. ARUP Consult: Respiratory Syncytial Virus - RSV The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/respiratory-syncytial-virus
  5. Lee N et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis 2013 Oct; 57:1069 PMID: 23876395 http://cid.oxfordjournals.org/content/57/8/1069
  6. McLellan JS et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science 2013 Nov 1; 342:592 PMID: 24179220 http://www.sciencemag.org/content/342/6158/546.1
  7. DeVincenzo JP et al. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med 2014 Aug 21; 371:711 PMID: 25140957 http://www.nejm.org/doi/full/10.1056/NEJMoa1401184 - Wright PF. Progress in the prevention and treatment of RSV infection. N Engl J Med 2014 Aug 21; 371:776 PMID: 25140965 http://www.nejm.org/doi/full/10.1056/NEJMe1407467
  8. Ralston SL et al Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis Pediatrics. October 27, 2014 PMID: 25349312 http://pediatrics.aappublications.org/content/early/2014/10/21/peds.2014-2742.full.pdf+html
  9. Griffiths C, Drews SJ, Marchant DJ Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment. Clin Microbiol Rev. 2017 Jan;30(1):277-319. PMID: 27903593 PMCID: PMC5217795 Free PMC article
  10. Bronze MS Fast Five Quiz: Respiratory Syncytial Virus (RSV). Medscape. Nov 8, 2022 https://reference.medscape.com/viewarticle/983643
  11. RSV in Adults https://www.rsvinadults.com - Older adults are at high risk for severe RSV infection. Centers for Disease Control and Prevention. Accessed June 23, 2022. https://www.cdc.gov/rsv/high-risk/older-adults.html
  12. Krilov LR, Steele RW Respiratory Syncytial Virus Infection. Medscape. Updated Nov 21, 2022 https://emedicine.medscape.com/article/971488-overview
  13. Moderna. Jan 17, 2023 Moderna Announces mRNA-1345, an Investigational Respiratory Syncytial Virus (RSV) Vaccine, Has Met Primary Efficacy Endpoints in Phase 3 Trial in Older Adults. https://investors.modernatx.com/news/news-details/2023/Moderna-Announces-mRNA-1345-an-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Has-Met-Primary-Efficacy-Endpoints-in-Phase-3-Trial-in-Older-Adults/default.aspx
  14. Surie D, Yuengling KA, DeCuir J et al. Disease severity of respiratory syncytial virus compared with COVID-19 and influenza among hospitalized adults aged >= 60 years - IVY Network, 20 U.S. States, February 2022-May 2023. MMWR Morb Mortal Wkly Rep 2023 Oct 6; 72:1083. https://www.cdc.gov/mmwr/volumes/72/wr/mm7240a2.htm - Havers FP, Whitaker M, Melgar M, et al. Characteristics and outcomes among adults aged >= 60 years hospitalized with laboratory-confirmed respiratory syncytial virus - RSV-NET, 12 states, July 2022- June 2023. MMWR Morb Mortal Wkly Rep 2023 Oct 6; 72:1075. https://www.cdc.gov/mmwr/volumes/72/wr/mm7240a1.htm
  15. Woodruff RC, Melgar M, Pham H et al Acute cardiac events in hospitalized older adults with respiratory syncytial virus infection. JAMA Intern Med 2024 Apr 15; [e-pub] https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2817609
  16. Alfano F, Bigoni T, Caggiano FP et al. Respiratory Syncytial Virus Infection in Older Adults: An Update. Drugs Aging. 2024. May 4. PMID: 38713299 Review. https://link.springer.com/article/10.1007/s40266-024-01118-9
  17. Surie D et al. RSV vaccine effectiveness against hospitalization among US adults 60 years and older. JAMA 2024 Sep 4; [e-pub]. PMID: 39230920 PMCID: PMC11375516 (available on 2025-03-04) https://jamanetwork.com/journals/jama/fullarticle/2823011
  18. Branche AR et al. Residency in long-term care facilities: An important risk factor for RSV hospitalization. J Infect Dis 2024 Aug 23; [e-pub]. PMID: 39177782 https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiae424/7739867