Challenges and Progress in Understanding and Combating Respiratory Syncytial Virus Infection

Immunity to respiratory syncytial virus (RSV) is complex and multifactorial, involving both innate and adaptive immune responses that interact with viral pathogenicity to determine the outcome of infection. With a better understanding of these mechanisms, new therapeutic and prophylactic strategies are being developed to combat RSV infection according to research compiled in the Official Journal of the Spanish Society of Chemotherapy. 

RSV infection has evolved with new diagnostic tests making it easier to identify, affecting patients of all ages and immunocompromised individuals, with a potential for more severe cases in the elderly. Treatment and prevention options, such as vaccines and monoclonal antibodies, are available for severe cases, necessitating increased awareness and action from health care professionals and authorities.

The COVID and Emerging Pathogens Committee of the Illustrious College of Physicians of Madrid (ICOMEM) has recognized the importance of addressing these changes, posing questions to both committee members and external experts to better understand the situation in Spain and the response of the Health Authorities. The outcome of these discussions highlights the need for proactive measures to combat RSV and other emerging pathogens, requiring significant financial support and a unified approach in health care.

The concept of the "exposome," which includes factors from prenatal development that contribute to chronic lung diseases, has gained attention in recent years. RSV infection in early life has been linked to a higher risk of asthma in children and young people, as well as an increased risk of chronic obstructive pulmonary disease (COPD) in adults. The mechanisms by which RSV infection may lead to asthma include increased allergen absorption, production of specific antibodies, and persistent inflammation. While some studies suggest a link between RSV bronchiolitis in infancy and asthma, further research is needed to fully understand this relationship.

Patients with COPD have a higher incidence of RSV infection, leading to increased inflammatory activity in the airways. Structural changes in the lungs due to RSV infection in early life may enhance the risk of COPD development. Recent epidemiological studies have shown a relationship between childhood RSV infection and altered respiratory function or premature death from chronic respiratory diseases, prompting further research into the link between RSV and chronic respiratory diseases.

New data from Spain and the US have shown high mortality rates in elderly RSV patients compared to flu patients, emphasizing the need for better diagnosis and targeted therapy in this population. Recognition of RSV as a significant threat in older adults could lead to improved management practices and reduced mortality rates in health care settings.

RSV infection is common in transplant patients, with higher incidence rates seen in hematopoietic cell and lung transplant recipients. Compared to immunocompetent individuals, transplant patients with RSV infection have a higher risk of morbidity and mortality. It is important to consider the signs and symptoms of RSV infection in immunosuppressed patients, as they may present differently. Preventive measures, such as strict infection control practices, are crucial in managing RSV infections in transplant patients given the limited treatment options available.

Respiratory viral infections can lead to bacterial superinfection by damaging respiratory epithelial cells and weakening the host's immune response, making them more susceptible to bacterial invasion. RSV is prone to polymicrobial infections, especially in cases of pneumonia development. Therefore, in patients with worsening RSV infection, it is important to consider the possibility of bacterial superinfection and initiate appropriate antibiotic treatment promptly. Coinfections in hospitalized patients can occur in up to 68% of cases, with common pathogens including Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, and others, leading to increased severity and mortality.

Efforts to develop a vaccine or immunoprophylaxis against RSV are actively ongoing, with Nirsevimab and Abrysvo being the first available agents for preventing pediatric RSV infection. Different types of vaccines in development against RSV include mRNA-based vaccines, subunit, and particulate vaccines, live attenuated or chimeric vaccines, and recombinant vector-based vaccines. 

Older adults, those with chronic health conditions, and individuals living in nursing homes are at increased risk of severe RSV disease. Several phase 3 studies have shown promising results for vaccines targeting the F protein, with high efficacy in preventing RSV-associated lower respiratory tract disease. FDA approval has been granted for two vaccines, RSVPreF3 and RSVpreF, for adults over 60 years, with positive recommendations from the CDC and EMA. 

Cost-effectiveness analyses in different populations are ongoing to assess the potential impact of widespread vaccination programs for RSV in older adults. Despite the promising results, further research is needed to fully understand the health and economic implications of RSV vaccination in different populations.

Reference 
Ruiz-Galiana J, Cantón R, De Lucas Ramos P, et al. Respiratory syncytial virus: a new era. Oficial de la Sociedad Espanola de Quimioterapia. 2024:37(2);134–148. doi:10.37201/req/147.2023