Considerations for RSV Prevention in Special Patient Populations

Introduction

Respiratory syncytial virus (RSV) is the leading cause of serious airway infections globally.¹ This enveloped, non-segmented, negative-strand RNA virus of the Paramyxoviridae family is highly contagious and transmitted through respiratory droplets that enter the body through the eyes, nose, or mouth.² The clinical presentation of this virus ranges from common cold symptoms to a serious respiratory illness with complications often requiring hospitalization.³ In mild cases, the infection is self-limiting and the patient recovers within several weeks.

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Older adults, patients with weakened immune systems, individuals living in long-term facilities, and those with underlying cardiopulmonary disease are at a higher risk of developing severe RSV infection outcomes.^3,4 This includes development of bronchiolitis or pneumonia because the virus spreads to the lower respiratory tract. Symptoms include wheezing and chest-wall retractions, as well as cyanosis and tachypnea. Extrapulmonary manifestations of RSV disease can occur, such as sepsis-like syndrome and arrhythmias.⁵ An intensive care unit (ICU) admission and/or mechanical ventilation may be required in these critical cases.⁶

Severe RSV may be life-threatening in older adults. In the US, there are an estimated 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths annually due to RSV among those who are 65 years of age and older.⁷ Therefore, vaccination is recommended for prevention in this special patient populations.

Vaccines and Special Patient Populations

RSV vaccines were approved by the FDA in May of 2023. Subsequently, the CDC announced that individuals aged 60 and older who are at risk for becoming extremely ill from RSV obtain the vaccine.⁸ Moreover, pregnant patients are also encouraged to get immunized and maternal RSV vaccination was approved by the FDA in August 2023.⁸

There are 2 vaccines available: RSVPreF (Abrysvo; Pfizer) and RSVPreF3 (Arexvy; GSK). Both formulations are recombinant protein vaccines, which induce an immune response against RSV fusion (F) glycoprotein to protect against lower respiratory tract disease caused by RSV. The F protein causes the virion membrane to fuse with the target cell membrane, allowing for virus spread.⁹ The F protein also remains the major target for future antiviral drug development.⁹

RSVPreF is a bivalent recombinant stabilized prefusion F protein subunit vaccine that contains equal amounts of stabilized prefusion (preF) antigens from both RSV A and RSV B.¹⁰ RSVPreF3 includes an adjuvant, which is required at the time of vaccine administration for reconstituting the vial of lyophilized recombinant RSV glycoprotein F stabilized in prefusion conformation as the antigen component. The adjuvant enhances the immune response to the vaccine.¹¹ Both immunizations are administered as a single intramuscular injection into the deltoid muscle. Currently, only 1 dose is recommended and it is unknown whether seasonal doses will be required in the future.¹² Both vaccines are reported to be more than 80% effective at preventing severe RSV disease.¹³

Elderly Population Considerations

The RSV vaccine is recommended for adults aged 60 and older who have weakened immune systems and chronic conditions. The CDC recommends that this population obtain guidance from health care professionals about the benefits and risks of RSV immunization.¹² In this group, either RSVPreFor RSVPreF3 can be considered.⁴

Pregnant Population Considerations

Pregnant women can receive a vaccine while the fetus is in utero.¹⁴ The only immunization approved by the FDA during pregnancy is RSVPreF.¹⁵ This formulation is recommended to prevent severe RSV disease in infants from birth to 6 months of age. Patients that are 32 to 36 weeks pregnant can be inoculated during seasons where the prevalence of RSV is high. In the continental US, this is usually from September to January. Clinical studies have reported that maternal RSV vaccine uptake reduced the risk of severe disease in infants by 82% within 3 months and by 69% within 6 months following birth.¹⁵

Considerations, Contraindications, and Adverse Effects

Although vaccines are highly beneficial in the specific populations mentioned here, limitations do exist. Both RSVPreF and RSVPreF3 are contraindicated in patients who are allergic to any of the vaccine components. Moreover, if an individual is moderately to severely ill, immunization should be delayed until the patient recovers.¹² Additionally, it should be noted that clinical trials for these immunizations did not include patients with weakened immune systems. Therefore, immunocompromised individuals (including those with a cancer diagnosis and/or undergoing cancer treatment) should consult with a health care professional before receiving an RSV vaccine.¹⁶

There is limited information regarding the concurrent administration of the RSV with other vaccines (COVID-19, influenza, etc.). Although providing 2 vaccines in one day may be acceptable, there remains a possibility that vaccine coadministration may increase systemic or local reactions. Therefore, health care professionals should weigh vaccine administrations over multiple visits versus the risk of vaccine-preventable illness before deciding upon coadministration of the RSV vaccine with others.¹²

The most common adverse effects reported with both RSV vaccine formulations include pain at the injection site, headaches, myalgia, and nausea. A small number of cases of severe neurologic conditions were reported to occur in older adults during clinical trials. In the RSVPreF3 clinical trials, of the 17,922 participants, there was one case of Guillain-Barré syndrome (GBS) and 2 cases of acute disseminated encephalomyelitis.¹⁷ In the RSVPreF trials, of the 20,255 participants, there was 1 reported case of GBS, 1 case of Miller Fisher syndrome (a GBS variant), and 1 case of undifferentiated motor-sensory axonal polyneuropathy.¹⁷ Additionally, during clinical trials for both vaccines, there was a higher incidence of atrial fibrillation for those receiving the immunization compared to those who were administered the placebo.¹⁸ Due to limited data, it is unknown whether these adverse effects were a coincidence or caused by receiving the immunization.¹²

In RSVPreF clinical trials for patients 32 to 36 weeks pregnant, preterm births occurred in 4.2% of patients who received the RSV vaccine compared to 3.7% for those who received a placebo. It should be noted that women who were already at a higher risk of preterm births were excluded from the vaccine studies. Furthermore, a higher incidence of pre-eclampsia, low birth weight (less than 5.5 lb), and jaundice were observed in patients administered the RSV vaccine. However, there are insufficient data to determine a causal relationship between immunization and pregnancy outcomes. Overall, both vaccine manufacturers are required to conduct additional studies regarding the risk of adverse effects upon immunization.¹⁵

Conclusion

RSV is an enveloped, non-segmented, negative-strand RNA virus of family Paramyxoviridae. It is contagious and, despite its self-limiting nature, can spread to the lower respiratory tract in high-risk populations. The RSVPreF and RSVPreF3 vaccines are encouraged in these susceptible individuals to prevent severe illness. RSVPreF is the only RSV vaccine formulation currently approved in pregnancy.

Both formulations have the potential to help susceptible patients avoid hospitalizations and ultimately save thousands of lives. Due to the occurrence of adverse events in a small number of vaccine recipients, the CDC and FDA will continue to review data to observe the safety and efficacy of these RSV vaccines, along with updating criteria and eligibility for future use.

References

1. Stobbelaar K, Mangodt TC, Van der Gucht W, et al. Risk Factors Associated with Severe RSV Infection in Infants: What Is the Role of Viral Co-Infections? Microbiol Spectr. 2023;11(3):e0436822. doi:10.1128/spectrum.04368-22
2. Transmission of RSV (respiratory syncytial virus). Centers for Disease Control and Prevention. April 26, 2023. Accessed January 14, 2024. https://www.cdc.gov/rsv/about/transmission.html
3. Nguyen-Van-Tam JS, O'Leary M, Martin ET, et al. Burden of respiratory syncytial virus infection in older and high-risk adults: a systematic review and meta-analysis of the evidence from developed countries. Eur Respir Rev. 2022;31(166):220105. doi:10.1183/16000617.0105-2022
4. Respiratory syncytial virus (RSV). Mayo Clinic. October 4, 2023. Accessed January 14, 2024. https://www.mayoclinic.org/diseases-conditions/respiratory-syncytial-virus/symptoms-causes/syc-20353098
5. Checchia P. Identification and management of severe respiratory syncytial virus. Am J Health Syst Pharm. 2008;65(23 Suppl 8):S7-S12. doi:10.2146/ajhp080439
6. Atamna A, Babich T, Froimovici D, et al. Morbidity and mortality of respiratory syncytial virus infection in hospitalized adults: Comparison with seasonal influenza. Int J Infect Dis. 2021;103:489-493. doi:10.1016/j.ijid.2020.11.185
7. Transmission of RSV (respiratory syncytial virus). Centers for Disease Control and Prevention. April 26, 2023. Accessed January 16, 2024. https://www.cdc.gov/rsv/research/index.html
8. Respiratory Syncytial Virus (RSV) Immunizations. Centers for Disease Control and Prevention. August 30, 2023. Accessed January 14, 2024. https://www.cdc.gov/vaccines/vpd/rsv/index.html
9. McLellan JS, Ray WC, Peeples ME. Structure and function of respiratory syncytial virus surface glycoproteins. Curr Top Microbiol Immunol. 2013;372:83-104. doi:10.1007/978-3-642-38919-1_4
10. Abrysvo Prescribing information. Pfizer; 2023. https://www.fda.gov/media/168889/download
11. Arexvy Prescribing Information. GSK; 2023. https://www.fda.gov/media/167805/download
12. Healthcare Providers: RSV vaccination for adults 60 years of age and over. Centers for Disease Control and Prevention. August 30, 2023. Accessed January 14, 2024. https://www.cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html
13. Katella K. Should you get the new RSV vaccine? Yale Medicine. August 28, 2023. Accessed January 14, 2024. https://www.yalemedicine.org/news/should-you-get-the-new-rsv-vaccine
14. RSV in infants and Young Children. Centers for Disease Control and Prevention. August 4, 2023. Accessed January 14, 2024. https://www.cdc.gov/rsv/high-risk/infants-young-children.html
15. Healthcare Providers: RSV vaccination for pregnant people. Centers for Disease Control and Prevention. September 29, 2023. Accessed January 14, 2024. https://www.cdc.gov/vaccines/vpd/rsv/hcp/pregnant-people.html
16. What to know about the RSV vaccines: Who can get it, side effects, availability at MSK. Memorial Sloan Kettering Cancer Center. August 16, 2023. Accessed January 14, 2024. https://www.mskcc.org/news/what-to-know-about-rsv-vaccines-who-can-get-it-side-effects-availability-at-msk
17. 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. doi:10.15585/mmwr.mm7229a4
18. Harris E. FDA Clears RSV Vaccine for Adults Aged 60 Years or Older. JAMA. 2023;329(21):1817. doi:10.1001/jama.2023.8657