ERS 2022 Congress Highlights

Expert discussion

Join Professor Francesco Blasi, Professor of Respiratory Medicine at the University of Milan, Italy, and Dr Ting Shi, epidemiologist and Chancellor’s Fellow at the University of Edinburgh, UK, to learn about key topics relating to respiratory syncytial virus (RSV) infection in adults that emerged at the European Respiratory Society (ERS) 2022 Congress. Professor Blasi and Dr Shi share insights about the burden of RSV infection in adults, the impact of RSV infection during pregnancy and the consequences of RSV infection in adults. They delve into the challenges of diagnosis, treatment and prevention of RSV infection in adults, ending their discussion with key take-home messages from the ERS 2022 Congress.

What is the burden of RSV in adults at high risk of infection?

Dr Shi shares with the audience the burden of RSV infection in adults in the general population and high-risk groups, and Professor Blasi emphasises that RSV infection is of particular concern in frail patients.

• The incidence of RSV infection in adults with and without a high-risk profile is 6.7 per 1000 persons per year
• RSV positivity among hospitalised cases of acute respiratory infections is around 4.4%
• For adults with underlying health conditions the incidence of RSV infection is much higher (37.6 per 1000 persons per year) than for the general adult population
• In-hospital case fatality ratio in adults with comorbidities is much higher than for the general adult population (11.7%, compared with 1.6%)

What is the impact of RSV infection during pregnancy?

Dr Shi discusses the potential risks of RSV infection during pregnancy.

• RSV infection may pose a substantial risk of hospitalisation and further complications
• Infection is likely to be worse in pregnant women with underlying respiratory diseases, such as asthma, or who are tobacco users

What are the consequences of RSV infection in adults?

Professor Blasi and Dr Shi discuss the consequences for adults with RSV infection.

• RSV can cause severe infection, with complications in patients with comorbidities, including cardiovascular disease or respiratory conditions, such as asthma or chronic obstructive pulmonary disease (COPD)
• RSV infection can induce cardiovascular events like myocardial infarction or severe arrhythmia like atrial fibrillation potentially due to the impact of this infection on inflammation, as has been similarly observed with influenza

Challenges for diagnosis, treatment and prevention of RSV infection in adults

Professor Blasi and Dr Shi delve into the management of the active disease in an informative discussion about the challenges for diagnosis, limitations of current treatment and the anticipation for vaccines that are under investigation for prevention of RSV infection.

• Diagnosis requires an awareness of RSV and the use of laboratory tests, such as PCR or antigen testing, as it is difficult to differentiate RSV infection from other viral infections solely on the basis of clinical features
• At present, there are no specific treatments for RSV and management consists of symptomatic relief, treatment of secondary infections and comorbidities, and supportive care
• Several RSV vaccines are under investigation in clinical trials and some may soon receive regulatory approval for prevention of infection

Key messages from ERS 2022 Congress

Professor Blasi and Dr Shi highlight the most relevant take-home messages from ERS 2022 Congress that relate to RSV infections in adults.

• There is high need for increasing the awareness about the disease affecting adults, particularly for frail patients and those with comorbidities, including cardiovascular, respiratory and renal disease, and diabetes
• The use of available diagnostic tools is critical for better management of the disease and improved outcomes
• General preventive measures, including personal hygienic practices, are key to minimising infection while waiting for other solutions such as RSV vaccines

Meet the experts

Professor Francesco Blasi

Francesco Blasi is Professor of Respiratory Medicine in the Department of Pathophysiology and Transplantation at the University of Milan, Italy, and Head of the Department of Internal Medicine and the Respiratory and Lung Transplantation Unit at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan. He is also Director of the Adult Section of the Lombardia Regional Cystic Fibrosis Referral Centre in Milan.

Professor Blasi is a member of the Board of Directors of the University of Milan and, since 2019, Vice-President of the Italian Society of Cystic Fibrosis (SIFC). He is a past president of the European Respiratory Society (2012–2013), the Italian Respiratory Society (SIP; 2016–2017) and the SIP Research Centre (2017–2018).

Disclosures

Francesco Blasi reports grants and personal fees from AstraZeneca PLC, Chiesi Farmaceutici SpA, GlaxoSmithKline PLC, the Menarini Group and Pfizer Inc., as well as personal fees from Grifols SA, Laboratori Guidotti SpA, Insmed Inc., Novartis International AG, Sanofi Genzyme, Vertex Pharmaceuticals Inc., Viatris Inc., Janssen, and Zambon Pharma.

Dr Ting Shi

Dr Ting Shi is a Chancellor's Fellow at The University of Edinburgh. She obtained her PhD and MPH degrees in Public Health Sciences from the University of Edinburgh. She is an epidemiologist with a particular interest in global respiratory epidemiology, including respiratory syncytial virus (RSV) and COVID-19. Within and beyond her Chancellor’s Fellowship, she will continue developing her career in the field of respiratory epidemiology and related health services research and modelling.

Disclosures

None.

Day One Highlights – RSV and adults

By Ben Gallarda, PhD

Understanding RSV: Identifying high risk adults

The 2022 European Respiratory Society (ERS) International Congress began bright and early on Sunday 4 September with a series of Industry Early Morning Symposia. In keeping with aim of the Respiratory Syncytial Virus (RSV) in Adults Learning Zone, this series of 3 daily congress highlight articles will provide a thorough overview of all RSV-related data presented at ERS 2022. This first article covers the industry symposium sponsored by Janssen with content produced by the independent experts involved, focusing on ‘Understanding RSV: Identifying high risk adults’¹.

Professor Francesco Blasi opened the symposium highlighting its two primary objectives:

1. To understand the disease burden of RSV acute respiratory infection (ARI) in adults with comorbidities
2. To gain an understanding of how RSV can affect older adults and its impact on healthcare utilisation

Understanding RSV: Burden of disease in high-risk adults

Dr Ting Shi presented recent research from her group aimed at estimating the disease burden of RSV-related ARI in adults with comorbidities². Previous research showed that industrialised countries saw an estimated 1.5 million RSV-ARIs in 2015, a hospitalisation rate of 14.5%, and approximately 14,000 deaths³.

The focus of Dr Shi and her colleagues’ present work is a similar systematic review and meta-analysis (with limitations typical of these types of studies) of RSV-ARI burden, but in adults with a least one comorbidity instead of the general population, and using adults without comorbidities as a control group⁴. Table 1 shows the main results of this analysis based on the available studies from industrialised countries (n = 2–7 of 20 total studies meeting inclusion criteria).

Table 1. Primary results of meta-analysis of RSV-ARI incidence in adults with comorbidities.

Compared to the general population, both the incidence and hospital case fatality ratio (hCFR) in adults with comorbidities is higher – 37.6/1000 persons/year vs 6.7 and 11.7% vs 1.6%, respectively. One caveat is that incidence rates show overlapping 95% confidence intervals, so more studies are need to verify that this large increase is accurate. For comparison, even influenza’s hCFR in adults 50–64 years of age, with or without comorbidities, is 1.3–5.6%⁵.

RSV and chronic respiratory diseases: What are the consequences?

The second presentation featured Dr Marc Miravitlles turning the symposium’s attention to chronic respiratory comorbidities, in particular,  their effects on risk related to RSV infections in adults⁶. He pointed out that viral infections not only cause substantial issues in patients with respiratory disease such as chronic obstructive pulmonary disease (COPD), but also ‘opens the door’ to bacterial and other infections that can cause further respiratory problems.

After a thorough review of previous data on the relationship between RSV infections and respiratory comorbidities, Dr Miravitlles showed several datasets from published literature showing the greater impact of RSV infection compared to influenza in time of hospital stay, upper and lower respiratory infections, rates of pneumonia, respiratory failure, and even mortality.

The burden of RSV in patients with existing respiratory diseases is substantial, possibly greater than that of influenza and other, more commonly researched respiratory viral infections

Q&A

In an engaging question and answer sessions, Professor Blasi and Drs Shi and Miravitlles responded to queries from both the live audience and the online community attending the symposium. They discussed the benefits of managing RSV in childhood on the risks of RSV to adults – preventing RSV in children would likely reduce adverse events occurring in adulthood. Dr Shi reviewed best practices for diagnosing RSV – PCR vs antigen testing, and the increased acceptability of doing a nasal swab on a patient, compared to previous years. Finally, the three symposium participants discussed the benefits of continued masking, particularly in seasons of increased risk for RSV infection and recommended that at-risk patients regularly wear masks when in public or in environments where viral transmission is more likely. Dr Miravitlles expressed his hope that, similar to COPD patients carrying oxygen bottles, wearing of masks in public may have less stigma today than previously.

Main takeaways

• RSV infection carries a substantially higher risk of adverse events and mortality in patients with any comorbidity, but especially those with respiratory diseases such as asthma and COPD
• Further research is needed to verify the estimates of the burden of RSV-ARI in both the general population and in adults with comorbidities
• Forthcoming treatments and preventative measures for RSV infection may go a long way in reducing the existing burden of RSV infection both in adulthood, and via childhood healthcare programmes.

By Sam Swingler, PhD

Day 2 began with two e-posters presenting data on respiratory syncytial virus (RSV) in the UK, predominantly in paediatric patients. First up was an e-poster submitted by Andrew Willard, which focused on the prophylactic treatment of children with neuromuscular diseases who are highly susceptible to contracting RSV. This was shortly followed by Professor Steve Cunningham who presented data analysing the 2021 aseasonal epidemic of RSV.

Prophylactic monoclonal antibody treatment for RSV in paediatric cohorts with neuromuscular diseases

Mr Andrew Willard and his team present data from an in depth literature review into the incidence of IgG1κ monoclonal antibody prophylaxis in children with neuromuscular diseases such as spinal muscular dystrophy⁷. Currently, the United Kingdom Green Book guidelines only recommend IgG1κ monoclonal antibody prophylaxis to prevent RSV in infants without neuromuscular diseases⁸. The data collected by Mr Willard and colleagues arises from surveys of UK-based health care professionals on the use of IgG1κ monoclonal antibody in paediatric patients with neuromuscular diseases, and from reviewing published research into risks of RSV in infants, and the role that IgG1κ monoclonal antibodies have in infants with neuromuscular disease.

Of the 34 identified research journals found, the team identified four key themes:

1. Seven of 34 publications identified that neuromuscular disease is a severe risk factor in developing RSV. A multicentre database study from Germany found that the neuromuscular disease group were more frequently ventilated than the non-neuromuscular disease group (9.6% vs 1.9%).
2. Two studies found that neuromuscular disease in infants is a potentially high risk factor for mortality in cases of severe RSV with an attributable mortality rate of 5.5% vs 0.2% in those without (P<0.001).
3. The median age of infants that present with RSV occurs later in infancy in those with neuromuscular diseases than those without, 14 vs 6 months, respectively.
4. Ten studies identified the use of IgG1κ monoclonal antibody as an appropriate prophylactic treatment for infants with neuromuscular disease to combat the risk of RSV infection.

There is substantial evidence of the risk of severe RSV infection in children with neuromuscular disease

The team concluded that there is substantial evidence for the use of IgG1κ monoclonal antibody prophylactic treatment in infants with neuromuscular disease against RSV, however, there is still an absence of randomised control studies for the use of IgG1κ monoclonal antibodies in this capacity. The survey also revealed that 53% of practitioners surveyed use IgG1κ monoclonal antibodies in infants with spinal muscular atrophy type 1 to protect from RSV infection.

Aseasonal 2021 RSV epidemic

Professor Steve Cunningham and his team then presented their poster based on the prospective multi-centre cohort BronchStart study⁹. Paediatric emergency departments (PED) within PERUKI (Paediatric Emergency Research in the UK and Ireland) submitted data on all children under 2 years of age who visited an emergency department with symptoms of an acute lower respiratory tract infection (diagnosed as bronchiolitis – 80.8%, lower respiratory tract infection – 8.5%, or first episode of acute wheeze – 10.7%), to a secure online Research Electronic Data Capture (REDCap) database¹⁰.

In their e-poster, data for 17,838 cases in 17,099 individuals for the period from 1 June to 5 December 2021 was presented. Comparing the age distribution of hospitalised infants <12 months to previous years at two large paediatric centres currently participating in the BronchStart Study, Professor Cunningham and his team observed a similar age distribution. They also observed a substantial number of PED visits and admissions for RSV-positive 12–23 month old children: 362 out of 1,468 (24.7%) admissions were in this age group.

The team were also able to show that the overall lower burden of disease in 2021 suggests incomplete infection by RSV of its usual susceptible population which is speculated to be caused by the ongoing non-pharmaceutical interventions over the study time period, and raises the strong possibility of a further wave of infection in coming months.

By Sam Swingler, PhD

Day 3 concluded with a late breaking presentation from Ms Annefleur Langedijk and her university supervisory team, University Medical Centre Utrecht, focused on the paradox of utilising either nasopharyngeal swabs (NPS) or saliva swabs in the diagnosis of respiratory syncytial virus (RSV)¹¹. It was reported that nasopharyngeal swabs are considered the gold standard for the diagnosis of RSV. Although highly sensitive, NPS come with several issues, namely:

• sampling burden
• lengthy delay between sampling and PCR result
• high personnel and resource costs

A saliva-based method for RSV detection would make large-scale sampling more feasible and less onerous

Detection of RSV was evaluated in paired NPS and saliva samples. Matched NPS and saliva samples were obtained by trained professionals taken from hospitalised infants with diagnosed viral respiratory infections. The obtained NPS and saliva samples were then tested with a saliva-based PCR test authorised by the FDA.

The team concluded the presentation with their study results, showing that 29 paired samples were collected from infants with medically-attended respiratory infections. As a proof of concept, the team analysed the first 10 samples, including five samples from RSV positive infants and five from infants with other respiratory viruses. RSV, rhinovirus, and enterovirus could be detected in all ten samples in both NPS and saliva. More notably, it was shown that there was significant discomfort when collecting NPS compared to saliva.

It was concluded that as RSV was detected in all samples taken, saliva is a viable method for the collection and diagnosis of RSV from infants and children. Additionally, there was emphasis on the fact that as saliva-based tests offer significant reduction in stress and discomfort, it should be a preferential method of collection, and could allow for frequent repeated testing. With further validation, widespread implementation of saliva sampling could transform RSV diagnosis and surveillance in children.

The study demonstrated significant discomfort when collecting NPS compared to saliva  

References

1. Blasi F, Shi T, Miravitlles M. Understanding RSV: Identifying high risk adults. Presented at the European Respiratory Society International Congress 2022, 4 September. Barcelona. Industry Early Morning Symposium.
2. Shi T. Understanding RSV: Burden of disease in high-risk adults. Presented at the European Respiratory Society International Congress 2022, 4 September. Barcelona. Industry Early Morning Symposium.
3. Shi T, Denouel A, Tietjen AK, Campbell I, Moran E, Li X, et al. Global Disease Burden Estimates of Respiratory Syncytial Virus-Associated Acute Respiratory Infection in Older Adults in 2015: A Systematic Review and Meta-Analysis. J Infect Dis. 2020;222(Supplement_7):S577–S583.
4. Shi T, Vennard S, Jasiewicz F, Brogden R, Nair H. Disease Burden Estimates of Respiratory Syncytial Virus related Acute Respiratory Infections in Adults With Comorbidity: A Systematic Review and Meta-Analysis. J Infect Dis. 2022;226(Suppl 1):S17-s21.
5. Kim DK, McGeer A, Uleryk E, Coleman BL. Burden of severe illness associated with laboratory confirmed influenza in adults aged 50-64 years: A rapid review. Influenza Other Respir Viruses. 2022;16(4):632-642.
6. Miravitlles M. RSV and chronic respiratory diseases: What are the consequences? Presented at the European Respiratory Society International Congress 2022, 4 September. Barcelona. Industry Early Morning Symposium.
7. Willard A, Axelton T, Jain K. Respiratory syncytial virus (RSV) infection in children with neuromuscular diseases (NMD): a literature review & a survey of Palivizumab prophylaxis in the UK. Presented at the European Respiratory Society International Congress 2022, 5 September. Barcelona. Thematic poster.
8. Axelson T, Willard A, Jain K1117 Survey of physician practice and opinions regarding the use of palivizumab as RSV prophylaxis, including in children with SMA Type 1. Archives of Disease in Childhood 2022;107:A246.
9. Cunningham S, Roland D, Williams T. Features of an aseasonal 2021 RSV epidemic in the UK and Ireland: analysis of the first 10,000 patients. Presented at the European Respiratory Society International Congress 2022, 5 September. Barcelona. Thematic poster.
10. Lyttle MD, O’Sullivan R, Hartshorn S, et al. Pediatric Emergency Research in the UK and Ireland (PERUKI): developing a collaborative for multicentre research. Arch. Dis. Child. 2014;99(6):602-603.
11. Langedijk A. Late Breaking Abstract - Saliva as an alternative to nasopharyngeal swabs for detection of respiratory syncytial virus (RSV) in children. Presented at the European Respiratory Society International Congress 2022, 5 September. Barcelona. Oral Presentation.