September/October 2024

September/October 2024 Issue

The Latest on RSV
By Mark D. Coggins, PharmD, BCGP, FASCP
Today’s Geriatric Medicine
Vol. 17 No. 5 P. 22

What Patients Need to Know About This Sometimes Severe Illness

The respiratory syncytial virus (RSV) is a common and significant contributor to respiratory illness across all age groups. RSV symptoms in healthy people usually include mild flulike systems like cough, runny nose, and mild fever. However, in older adults and persons with weakened immune systems, RSV infection can lead to more severe symptoms, including shortness of breath and pneumonia, leading to hospitalization and even death. In fact, according to the CDC, each year, an estimated 60,000 to 160,000 older adults in the United States are hospitalized due to RSV infection, and 6,000 to 10,000 die.1

Recent epidemiological research indicates that persons aged 75 and older, as well as adults between 60 and 74 years old with specific risk factors such as lung and heart disease, are more susceptible to severe RSV-related illness.2 This data reflects the need to prioritize vaccination efforts in this high-risk population to prevent severe illness and reduce the burden on health care systems. Thus, on June 26, 2024, the CDC updated its guidance on RSV vaccination to include all adults aged 75 and older and all adults aged 60 to 74 at increased risk of severe RSV disease.3 This updated recommendation for people aged 60 and older replaces the recommendation made last year to simplify RSV vaccine decision-making for clinicians and the public.

RSV History and Virology
RSV was initially identified in 1956 in 14 chimpanzees suffering from cold and coryza symptoms and was initially termed chimpanzee coryza agent.4 In 1957, it was isolated from infants and recognized as a human virus and a causal factor of lower respiratory illness in children.5 The virus was renamed as respiratory syncytial virus due to the formation of syncytia, which are large cells created when the virus fuses with the cells it invades. Our knowledge of RSV’s biochemical and molecular characteristics was limited until 1981, when the molecular cloning and sequencing of RSV RNA were accomplished.6

RSV is a virus belonging to the family Paramyxoviridae and is characterized as being enveloped, nonsegmented, and having a negative-strand RNA. This family of viruses includes the human metapneumovirus, pneumovirus, and measles. The cell membrane of RSV consists of two major surface glycoproteins: the G protein, which facilitates viral attachment to host ciliated cells of the airway, and the F protein, which mediates virion and host cell fusion.7 RSV has two subgroups, A and B, defined by glycoprotein G, with subgroup A being more prevalent and causing more severe disease.8 RSV utilizes F protein to merge with the host cell membrane and undergo a complete transformation from its prefusion RSV F state to its postfusion form, allowing it to enter the cell—a process essential for the virus to replicate and cause infection.7 In 2013, the NIH discovered the crystal structure of prefusion RSV F, enabling researchers to develop methods to prevent the prefusion form from transitioning to the postfusion form, allowing for the development of new RSV vaccines.8 Two new RSV vaccines, approved by the FDA in May 2023, feature the RSV F stabilized in its prefusion (pre-F) state. This design allows the vaccines to trigger the creation of neutralizing antibodies, engage both humoral and cellular immune responses, and foster the development of memory B and T cells.

Seasonality
In most regions of the United States and other areas with similar climates, RSV season typically starts during the fall and peaks in the winter. Although, the timing and severity of RSV season in a given community can vary from year to year. Florida has an earlier RSV season onset and longer duration than most regions of the country.

According to data from 2014-20179:

• RSV season onset (indicating a sustained rise in RSV-positive tests) ranged from mid-September to mid-November.

• RSV season peak (indicating the maximum number of RSV-positive tests) ranged from late December to mid-February.

• RSV season offset (indicating a sustained drop in RSV-positive tests) ranged from mid-April to mid-May.

Immune Response
Despite being highly contagious, RSV does not elicit a robust immune memory.10 While some immunity can be gained following RSV infection, individuals frequently encounter repeated infection and may contract RSV more than once in a single season. The virus’s capacity for reinfection is also attributed to its continual evolution and capability to evade the immune system.

Symptoms
Most people will develop symptoms within four to six days of RSV infection and may be contagious for three to eight days, beginning a day or two before symptoms appear.11 However, infants and those with weakened immune systems may continue to spread the virus for four weeks despite symptoms being resolved.11

Most older adults with RSV will be symptomatic with symptoms that range from mild to severe and may include the following:

• stuffy and runny nose;
• cough (wheezing cough);
• sore throat;
• fever; and
• fatigue and overall weakness.

Additionally, some individuals may develop pneumonia and worsening chronic respiratory conditions such as asthma and COPD. RSV infections can also be complicated by concomitant bacterial or viral coinfections in up to 21% to 23% of cases, with enhanced risk of death and severe disease.12

Symptoms that may indicate an older adult may need to call their doctor or go to the emergency department (ED) include the following:

• significant wheezing;
• trouble catching breath;
• tightness in the chest;
• extreme tiredness;
• high fever;
• coughing intensely; and
• lips or nails are blue.

In the most severe cases, a person may require additional oxygen, IV fluids if they can’t eat or drink enough, or intubation with mechanical ventilation.

Differences Between RSV and Influenza
Symptoms of RSV infection in older adults are like those of influenza or other respiratory viruses. However, some symptoms may be more suggestive for one of the pathogens. High fever is associated more often with flu, while malaise, asthenia, myalgia, and gastrointestinal symptoms are less common in RSV infection than with influenza.13 Compared with influenza, RSV hospitalized adults have more extended stays (six days vs 3.6 days) and morbidity.14 RSV patients are also more likely to develop pneumonia than are influenza or non-RSV patients.15

Transmission
RSV can be spread directly and indirectly. It’s transmitted primarily through direct contact with respiratory secretions from an infected individual, such as when they cough, sneeze, or talk, releasing tiny droplets that others can inhale. Additionally, the virus—which can live for several hours on hard services—can be transmitted by touching surfaces RSV and then touching one’s nose, mouth, or eyes.

Diagnosis
Two types of tests are commonly used to diagnose RSV infections16:

• Rapid RSV antigen tests are the most common test for RSV. The test uses a nasal swab sample to check for antigens that trigger the immune system response from RSV. Results are provided in an hour or less.

• RT-PCR (polymerase chain reaction) tests for genetic material from a nasal swab sample. The test can find smaller amounts of virus than antigen tests. Samples are usually sent to a lab for testing.

Prevention
Preventing RSV infections requires a combination of personal measures and community efforts. Clinicians can advise their patients about the recommended steps for slowing the spread of RSV and other viruses, which are to regularly wash hands with soap and water or use hand sanitizer, avoid touching faces, avoid sick individuals, stay home if ill, cover coughs and sneezes, disinfect surfaces, and consider wearing a mask in public for high-risk individuals. Additionally, older adults should prioritize their health by staying hydrated, eating well, exercising, resting, and getting vaccinated to prevent infections.

Vaccination
Vaccination is the most effective means of preventing RSV infections and reducing the associated disease burden.

FDA-Approved Vaccines
There are three FDA-approved RSV vaccines approved for adults aged 60 and older3 :

• AREXVY from Glaxo Smith Kline (GSK) was licensed by the FDA in 2023 and consists of recombinant RSV F protein antigen (based on the RSV-A subtype).

• ABRYSVO from Pfizer was licensed by the FDA in 2023 and consists of a recombinant RSV F protein antigen (based on the RSV-A and RSV-B subtypes).

• mRESVIA from Moderna was recently approved in June 2024 and consists of nucleoside-modified mRNA encoding the RSV F glycoprotein (monovalent, based on the RSV-A subtype).

How Effective Are RSV Vaccines?
CDC data from the first season of use showed that RSV vaccines provided protection against hospitalization, critical illness (ICU admission and death), and ED visits among people aged 60 and older.3

During the 2023-2024 RSV season, in adults aged 60 and over:

• AREXVY was 77% to 83% effective in preventing RSV-associated hospitalization or ED encounters.

• ABRYSVO was 73% to 79% effective in preventing RSV-associated hospitalization or ED encounters.

How Long Are the Vaccines Effective?
In adults aged 60 years and older: GSK’s AREXVY has been shown to provide protection for up to two years, Pfizer’s ABRYSVO for up to two years, and Moderna’s mRESVIA for up to 1.5 years (or 19 months). Studies on the length of protection provided by the vaccines and the need for booster shots in older adults are ongoing.

Timing of Vaccination
Eligible adults can get an RSV vaccine at any time, but the best time to get vaccinated is in late summer and early fall before RSV usually spreads in communities. Since the vaccines are effective for two seasons, this recommendation is for those persons who were not vaccinated for RSV last year. If you have a moderate or severe illness, you should wait until you recover before receiving an RSV vaccine. You can get an RSV vaccine if you have a minor illness, such as a cold.

RSV Vaccine Recommendation Update
The previous recommendations from the CDC’s Advisory Committee on Immunization Practices suggested that adults aged 60 years and older receive a single dose of RSV vaccine using shared clinical decision-making—meaning patients and their physicians should discuss whether the RSV vaccine would be beneficial based on their health status, risk of severe RSV, clinical judgment, patient preference, and the safety of the RSV vaccine. As noted previously, on June 26, 2024, the CDC updated its RSV vaccination recommendation for older adults to prioritize those at the highest risk for serious illness from RSV.17 People aged 75 or older and those between 60 and 74 years old with certain chronic health conditions or living in a nursing home should get one dose of the RSV vaccine to provide an extra layer of protection. The new recommendations simplify the decision-making process for prescribers and patients, stating that all adults aged 60 and older with certain risk factors should receive the RSV vaccine.

Evidence Supporting the Updated Recommendation
Immunizations were available last year for the first time to protect people at increased risk for severe RSV. The updated recommendation was based on analyses of RSV disease burden among people aged 60 and older, as well as on RSV vaccine effectiveness and cost-effectiveness studies. Those studies included the first real-world data since RSV vaccines were recommended for people aged 60 and older.17

Once such study used includes data from the Respiratory Syncytial Virus–Associated Hospitalization Surveillance Network, examining characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with confirmed RSV from July 2022 to June 2023.2 Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were older than 75 years. The most common underlying medical conditions were obesity, COPD, congestive heart failure, and diabetes. Severe outcomes occurred in 18.5% of hospitalized patients older than 60 years. Overall, 17% of patients were admitted to an ICU, 4.8% required mechanical ventilation, and 4.7% died; 17.2% of all cases occurred in long term care facility residents. This data highlights the importance of prioritizing those at the highest risk for severe RSV disease, particularly those older than 75 years, long term care facility residents, and adults aged 60 to 74 with underlying medical conditions, including COPD and congestive heart failure.

Vaccine Side Effects
Possible adverse reactions to the RSV vaccine include discomfort, swelling, inflammation at the injection site, fatigue, fever, headache, nausea, diarrhea, and muscle or joint pain. These side effects are usually mild.3

During the June 2024 Advisory Committee on Immunization Practices meeting, the CDC and FDA presented new data suggesting a potential increased risk of GBS after RSV vaccination with two specific vaccines (Arexvy by GSK and Abrysvo by Pfizer). However, currently, more data is needed to confirm this association.

Risk for Severe Complications
Epidemiologic evidence indicates that all adults aged 75 or older and adults aged 60 to 74 with certain risk factors are at increased risk of severe RSV.3

The following conditions increase the risk of severe RSV:

• cardiovascular disease (eg, heart failure, coronary artery disease; congenital heart disease, excluding isolated hypertension);

• lung disease (eg, COPD, emphysema, asthma, interstitial lung disease, cystic fibrosis);

• advanced chronic kidney disease (eg, stages 4–5, dependence on hemodialysis or other renal replacement therapy);

• diabetes mellitus with end-organ damage (eg, diabetic nephropathy, neuropathy, retinopathy, or cardiovascular disease);

• severe obesity (body mass index ≥40 kg/m2);

• liver disorders (eg, cirrhosis);

• neurologic or neuromuscular conditions (eg, neuromuscular conditions causing impaired airway clearance or respiratory muscle weakness, excluding history of stroke without impaired airway clearance);

• hematologic disorders (eg, sickle cell disease, thalassemia); and

• moderate or severe immune compromise (either attributable to a medical condition or receipt of immunosuppressive medications or treatment). The following people are also at risk:

• those with three or more symptoms of frailty: unintentional weight loss, exhaustion, weakness, slow walking speed, and low physical activity;

• those in nursing homes as well as adults aged 60 to 74 in retirement/independent living communities with specific high-risk medical conditions; and

• those with other chronic medical conditions or risk factors that a health care provider determines might increase the risk of severe disease due to respiratory infection.

Role of Health Care Professionals
Health care professionals can take steps to help improve RSV vaccination rates by patients. This includes educating patients about the importance of RSV vaccination, addressing any concerns or misconceptions they may have, and providing convenient access to vaccines. Additionally, health care professionals can collaborate with other organizations to raise awareness about RSV and its potential complications. By working together, we can ensure that more patients are protected against this serious respiratory infection.

— Mark D. Coggins, PharmD, BCGP, FASCP, is a long term care expert and corporate pharmacy consultant for Touchstone-Communities, a leading provider of senior care that includes skilled nursing care, memory care, and rehabilitation for older adults throughout Texas. He’s a past director of the American Society of Consultant Pharmacists and was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the Excellence in Geriatric Pharmacy Practice Award.

References
1. Respiratory viruses and older adults Centers for Disease Control and Prevention website. https://www.cdc.gov/respiratory-viruses/risk-factors/older-adults.html. Updated March 1, 2024. Accessed July 2, 2024.

2. 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;72(40):1075-1082.

3. Healthcare providers: RSV vaccination for adults 60 years of age and over. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html. Updated July 3, 2024. Accessed July 2, 2024.

4. Blount RE Jr, Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med. 1956;92(3): 544-549.

5. Chanock R, Roizman B, Myers R. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA): isolation, properties, and characterization. Am J Hyg. 1957;66(3):281-290.

6. Collins PL, Fearns R, Graham BS. Respiratory syncytial virus: virology, reverse genetics, and pathogenesis of disease. Curr Top Microbiol Immunol. 2013;372:3-38.

7. McLellan JS, Ray WC, Peeples ME. Structure and function of respiratory syncytial virus surface glycoproteins. Curr Top Microbiol Immunol. 2013;372:83-104.

8. The action-packed search for stability: a breakthrough in the fight against RSV. Pfizer website. https://www.pfizer.com/news/articles/the_action_packed_search_for_stability_a_breakthrough
_in_the_fight_against_rsv. Accessed July 8, 2024.

9. Rose EB, Wheatley A, Langley G, Gerber S, Haynes A. Respiratory syncytial virus seasonality — United States, 2014–2017. MMWR Morb Mortal Wkly Rep. 2018;67:71-76.

10. Johansson C. Respiratory syncytial virus infection: an innate perspective. F1000Res. 2016;5:2898.

11. Respiratory syncytial virus (RSV). National Foundation for Infectious Diseases website. https://www.nfid.org/infectious-disease/rsv/. Updated June 2024.

12. Nam HH, Ison MG. Respiratory syncytial virus infection in adults. BMJ. 2019;10(366):l5021.

13. Branche AR, Falsey AR. Respiratory syncytial virus infection in older adults: an under-recognized problem. Drugs Aging. 2015;32(4):261-269.

14. Osei-Yeboah R, Spreeuwenberg P, Del Riccio M, et al. Estimation of the number of respiratory syncytial virus-associated hospitalizations in adults in the European Union. J Infect Dis. 2023;228(11):1539-1548.

15. Loubet P, Lenzi N, Valette M, et al. Clinical characteristics and outcome of respiratory syncytial virus infection among adults hospitalized with influenza-like illness in France. Clin Microbiol Infect. 2017;23(4):253-259.

16. National Library of Medicine. Respiratory syncytial virus (RSV) tests. MedlinePlus website. https://medlineplus.gov/lab-tests/respiratory-syncytial-virus-rsv-tests/. Accessed July 9, 2024.

17. CDC updates RSV vaccination recommendation for adults. Centers for Disease Control and Prevention website. https://www.cdc.gov/media/releases/2024/s-0626-vaccination-adults.html. Published June 26, 2024. Accessed July 9, 2024.