RSV: Measuring its Impact & Prevention wit

Respiratory Syncytial Virus (RSV)

Measuring The Impact & vaccine Prevention

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Epidemiology

Understanding RSV

The hidden epidemic

RSV and the body

Stop the Spread

Vaccine

How does the vaccine work & how efficient is it?

Protect yourself and others

More RSV Content

Risk Factors

Who is at greater risk?

Podcasts, Interactive Game & Resources

©2023 American College of Chest Physicians. No part of this publication may be reproduced/used in any manner without permission from the publisher.

Understanding RSV

How the Body Fights RSV

RSV's Relationship to Influenza

Transmission & Immunology

Vaccine Mechanism

How RSV Infects the Body

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Stop the Spread

Avoid close contact with sick individuals

Stay home when sick

If you are not feeling well, stay home to protect others.

Avoid kissing, shaking hands, and sharing cups and eating utensils.

Droplet

PPE

Cover your coughs and sneezes with a tissue or your shirt sleeve, not your hands.

Nosocomial infections are possible with RSV, so gowns, gloves, masks, and eye protection should be used.

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Wash hands

Contact

Wash your hands often with soap and water for at least 20 seconds.

Clean frequently touched surfaces such as doorknobs and mobile devices.

Risk Factors

Solid Organ Transplant (SOT) Recipients

Co-morbidities

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Demographics

Place of Residence

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Season

Recovery

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Increased spread

Hematopoietic Stem Cell Transplant (HSCT) Recipients

Smoking

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Epidemiology

RSV: The Hidden Epidemic

5-16%

10-13%

Most infected by this age

Mortality in solid organ transplant (SOT) recipients requiring hospitalization

Mortality in hematopoietic stem cell transplant (HSCT) recipients requiring hospitalization

6,000 to 10,000

60,000 to 100,000

5%

5%

Respiratory infections in older adults (~7% in high-risk adults)

Population that are asymptomatic

Number of hospitalizations per year

Number of deaths per year

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Borchers et al Clin Rev Allergy Immunol. (2013): doi:10.1007/s12016-013-8368-9 Thompson et al, JAMA (2003): doi.org/10.1001/jama.289.2.179 Matias et al, Influenza Other Respi Viruses (2014): doi.org/10.1111/irv.12258 Hansen et al, JAMA Network Open (2022): doi.org/10.1001/jamanetworkopen.2022.0527

The Vaccine

How it works...

The GSK and Pfizer vaccines use the prefusion form of the RSV glycoprotein as their main antigen. This protein is highly conserved between PSV-A and RSV-B. The vaccine trials appear to have equivalent efficacy against both subtypes. Adjuvants act as immune co-stimulants along with the vaccine antigen, with a goal of increasing antibody levels and (when relevant) T-cell responses following vaccination. Some adjuvants are associated with increased systemic side effects, not fewer. Adjuvants generally do not have an effect on vaccine shelf life (although some preservatives used in vaccines do have this function). While adjuvanted vaccines may provoke a febrile response, this is not the intended effect but rather a side effect of the boosted immune stimulus.

Month Post-Infection

Dose

82.6%

94.1%

Reduction in RSV LRTI in Phase 3 trial of RSVPREF3 OA trial

Efficacy vs severe LRTI in Phase 3 of RSVPreF3 OA trial.

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Papi A, Ison MG, Lee D-G et al, N Engl J Med 2023 DOI: 10.1056/NEJMoa2209604

More RSV Content

Interactive Game

RSV Resources

• Identifying the Impact of RSV in Adults

• Reviewing RSV in Immunocompromised Adults

• Adult Vaccines for Respiratory Syncytial Virus

Podcasts

Webinars

• RSV in Adults: Measuring the Impact

• RSV Vaccines for Adults: Who, Why, and How

How the Body Fights RSV

Alterations in cytokine production in response to RSV infection leads to a maladaptive response

Th2 Response

APC

CD8+T Cell

Image modified from Figure 4 Taleb, S.A., Al Thani, A.A., Al Ansari, K. et al. Human respiratory syncytial virus: pathogenesis, immune responses, and current vaccine approaches. Eur J Clin Microbiol Infect Dis 37, 1817–1827 (2018). Springer Nature. https://doi.org/10.1007/s10096-018-3289-4

How RSV Infects the Body

• RSV can infect all parts of the respiratory epithelium
• Infections occur all along the conducting airways
• Low TH1 response and high TH2 response drive eosinophil mediated airway inflammation

Neutrophil

Eosinophil

APC

Th2 Response

Image modified from Figure 4 Taleb, S.A., Al Thani, A.A., Al Ansari, K. et al. Human respiratory syncytial virus: pathogenesis, immune responses, and current vaccine approaches. Eur J Clin Microbiol Infect Dis 37, 1817–1827 (2018). Springer Nature. https://doi.org/10.1007/s10096-018-3289-4

Demographics

• Hospitalization rates are highest in Native American/Alaska Native, Black, Hispanic/Latino groups.
• Age:
• <2 and > 60

• More restricted T-cell receptor (ICR) repertoire and weak activation of T cells are some of the effects of aging - making adults highly susceptible to RSV.
• Older adults and immunosuppressed individuals shed the virus longer due to altered cellular immunity.
• High-risk elderly patients have the greatest risk of developing pneumonia and critical illness.

Nam HH, Ison MG BMJ (2019) doi:10.1136/bmj.l5021

Season

• Highest rate of occurrences happen between September and December.

CDC data. Slide from Epidemiology and Burden of Respiratory Syncytial Virus in Older Adults in the U.S. presented by Fiona Havers, MD, MHS, FIDSA, at June 23, 2022 Advisory Committee on Immunization Practices and available online at https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-06-22-23/04-rsv-havers-508.pdf

HSCT Recipients

• HSCT (and Lung Transplant) have the highest morbidity and mortality.
• Risk factors associated with LRTI or severe disease:

• Lymphopenia
• GVHD (particularly pulmonary)

• Myeloablative conditioning therapy

• Nosocomial outbreaks

• Up to 50% of cases
• Up to half develop pneumonia

Paulsen et al, Clin Chest Med (2017): DOI: 10.1016/j.ccm.2017.07.012 Champlin et al, Biol Blood Marrow Transplant (2001): DOI: https://doi.org/10.1053/bbmt.2001.v7.pm11777103 Neeman et al, Curr Infect Dis Rep (2015): DOI: https://doi.org/10.1007/s11908-015-0490-9 Kim et al, J Infect Dis (2014): https://doi.org/10.1093/infdis/jit832

Smoking

• The chemicals in tobacco smoke can suppress the body's immune response, making it harder to combat RSV.
• Smoking can lead to increased production of mucus in the airways, which can provide a favorable environment for the replication of RSV.
• Infants and young children who are exposed to secondhand smoke are at an increased risk of RSV infections.
• Smokers, particularly those with underlying respiratory conditions, are more likely to experience severe RSV-related symptoms if they become infected.

• Smokers who contract RSV are more likely to require hospitalization compared with non-smokers with the virus.

Place of Residence

• Increased risk in long-term care facility residents

Vaccine Mechanism

Can you identify the protein on the virus links to host cells by clicking in the corresponding box?

Correct! F-protein on the surface of virus links to host cells, changing conformation at the time of linking. Stopping fusion will inhibit infection.

Image modified from Figure 4 Taleb, S.A., Al Thani, A.A., Al Ansari, K. et al. Human respiratory syncytial virus: pathogenesis, immune responses, and current vaccine approaches. Eur J Clin Microbiol Infect Dis 37, 1817–1827 (2018). Springer Nature. https://doi.org/10.1007/s10096-018-3289-4

Nam HH, Ison MG, BMJ 2019 doi: 10.1136/bmj.l5021

Relationship to Influenza

RSV infection was associated with greater odds of

• Hospital length of stay ≥7 days (odds ratio [OR] = 1.5)
• Pneumonia (OR = 2.7)
• ICU admission (OR = 1.3)
• COPD exacerbation (OR = 1.7)
• Greater mortality within 1 year of admission (OR = 1.3)
• More subsequent hospitalizations

Ackerson et al. Clin Infect Dis. (2019): doi:10.1093/cid/ciy991

SOT Patients

• T cell immunity is key to viral clearance and recovery
• Lung transplant population best studied
• Lung transplants (and HSCT) have the highest morbidity and mortality
• Higher RSV-related morbidity and mortality

• Incidence 6-16%
• Accounts for 6-12% of respiratory viral infections causing lower respiratory tract infection
• Progresses to LRTI in 40%
• Risk factors for morbidity and mortality

• Young age (<2 years)
• Early post-transplant period
• Recent rejection

Milstone et al, Eur Respir J (2006): DOI: 10.1183/09031936.06.00105505 Peghin et al, Am J Transplant (2017): DOI: 10.1111/ajt.14042 Weigt et al, Semin Respir Crit Care (2011): DOI: Billings et al, JHLT (2002): DOI: 10.1016/s1053-2498(01)00405-3

Recovery

• Variable depending on the severity of acute disease.
• Majority recover without issue, but for those who develop lower respiratory infections requiring hospitalization recovery may be more protracted.

High Risk Populations

• Immunocompromised Hosts
• Annual incidence around 4-10%.
• The true impact of RSV in immunocompromised populations is unknown.
• Patients with COPD and Asthma
• At risk for developing exacerbations secondary to RSV infection.
• These patients may also require corticosteroids and bronchodilators.

• Congestive Heart Failure (CHF)
• Adults with CHF had 8.1 times greater rates of RSV hospitalizations than adults.
• Adults ≥65 years old with CHF were 3.5 times more likely to be hospitalized with RV than adults without CHF.
• Among adults <65 years old with CHF, the RSV rate was 14.3 times greater.

Anderson et al, Diagn Microbiol Infect Dis (2016): https://doi.org/10.1016/j.diagmicrobio.2016.02.025 Prasad et al, Clin Infect Dis (2020): https://doi.org/10.1093/cid/ciaa730 Kujawski et al, Plos One (2022): https://doi.org/10.1371/journal.pone.0264890 Branche et al, Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595

Transmission and Immunology

• Droplet transmission
• Aerosols up to 3 feet
• Fomites: stable on hard surfaces or hands for several hours
• Infections occur in the respiratory epithelium along all conducting airways--sinuses all the way down to the bronchioles (type 1 pneumocytes in the alveoli)

• Incubation: 2-8 days; contagious prior to clinical symptoms and up to 7 days
• Neutralizing antibodies wane over time; repeat infections common
• Anti-RSV IgG and IgA have 4x reduction in 75% of adults 1 year after infection
• T cell immunity key to viral clearance and recovery

Nam HH, Ison MG BMJ (2019) doi:10.1136/bmj.l5021