RSV: an update on prevention and management

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Respiratory syncytial virus, RSV, is a common disease, but one which our broader society has only become very aware about in recent times. It's partially because of the waves of infection that have been sweeping through communities, but it's also because of improved testing and vaccine options. There's been a lot of change for healthcare workers to stay abreast of and a lot of intricacy to understand. So it's timely that there's a new Australian Prescriber article out covering these changes. I'm David Liew and today joining me on the Australian Prescriber Podcast is Dr Linny Phuong, paediatric infectious diseases physician, vaccine researcher, and a passionate advocate in this space. Linny, thanks so much for joining me today.

Thanks, David, for having me.

So perhaps just run us through what RSV looks like in clinic, how it presents, and what other differentials we need to think about before we think about what to do about it?

Yeah, absolutely. So I think in terms of RSV, unfortunately it can be very nonspecific so it can present like any other cold, respiratory infection. So people can have mild cold-like symptoms and/or severe lower respiratory tract infections. In the population that I see, in particular in infants, it is a leading cause of bronchiolitis. So children can present with wheeze, cough and particularly difficulty feeding in the younger ones. And then we know in adults as well, particularly those who are elderly or those with comorbidities, there is that risk of pneumonitis, pneumonia. And in some instances it can trigger cardiac events and also exacerbate underlying conditions like COPD or heart failure. So certainly there is a broad spectrum of signs and symptoms. In terms of differentials, it's any of the respiratory viruses and/or secondary bacterial infection in terms of respiratory conditions. With regards to ‘paedes’ [paediatric patients] there are so many other things that can be at play. So yeah, it'll be important today to talk about testing as well.

So before we get to that, I'm really interested in this idea that we see with a lot of respiratory infections that there's a lot of people who are affected, but there's this really pointy end leading to severe disease and complications. Tell me who's at risk of that. Who should we really be worried about?

Yeah, of course. So the high-risk groups, particularly in paediatrics, are infants who are born premature, those with underlying cardiac or respiratory conditions or neurological conditions. Then in the older adults, we think about adults over 60 to 65, those of Aboriginal and Torres Strait Islander background, and also those who are immunocompromised, particularly those who have had a transplant, for example, or are on immunosuppression. We also know that those with metabolic conditions such as obesity, diabetes, and other chronic diseases increases the likelihood of severe outcomes. So yeah, there's quite a few people who can be affected by RSV. That's why protection is really important.

And how does that map out to the broader epidemiology of RSV in terms of who's getting it in the community?

So what we know in paediatrics is nearly all kids are affected with RSV by the age of 2. And that's really important when we talk about vaccination later. We know that 3 in 100 children in that first 5 years of life can require hospital care. And in terms of adults, we know that detection rates are around about 2 per 1,000 people annually. With regards to epidemiology, we know that in some of the more temperate regions of Australia, there is a seasonal pattern. We often see a peak in winter. So anywhere between April to September, timing actually varies in the more tropical areas of Australia.

So I guess we've got these seasonal waves in temperate areas. We've got a big reservoir of infection that can leak out to at-risk populations. This seems to be a really exciting time to be able to test better and to protect better?

Yeah. I think it's worth considering that routine testing isn't recommended and we only recommend really any sort of testing when it would change clinical management. So we know in high-risk or severely unwell patients, testing is really important to be able to distinguish between conditions like influenza and COVID-19 because of the availability of antivirals. And we know that in terms of testing, we do have rapid antigen tests, but there are also PCRs [polymerase chain reaction laboratory tests], and PCRs are actually preferred because of accuracy. So it's important to know that testing is available, but it's not something that we would do for everyone with a cold.

So where do you think rapid antigen tests sit in amongst all of this? Should we be recommending them to patients broadly or is it really those target areas where it might change management?

Yeah, I think some people are just curious. And rapid antigen tests are readily available now from pharmacies. So certainly people are testing regardless of what we recommend. But it's particularly important in those high-risk and severely unwell patients. And when they are that unwell, they generally come to hospital anyway, so PCRs are done in those instances.

And do you think that we are using PCRs appropriately now? Should we be using them more broadly? Should we be referring in for more? Or do you think it's about right?

There are 2 types of standard tests that we use in terms of PCRs. We use a short panel, which is RSV, COVID, flu, and then we [may] do an extended panel which essentially covers all of those plus many other viruses. So I think as I mentioned before, it's really important to be able to distinguish where antivirals are warranted [for COVID and influenza]. I think the other instance where sometimes it's helpful to test in terms of PCR or otherwise is to figure out whether there's coinfection because that may affect the prognosis in terms of whether or not a child, for example, presenting with bronchiolitis is more likely to progress onto requiring respiratory support in terms of oxygen and high flow. So sometimes that helps us make decisions. I know that we do do a lot of testing in the hospital setting. But again, I feel like there needs to be a balanced decision with regards to how it's going to actually add to your management.

And I guess we've become used to this idea of trying to find that right balance when we're thinking about how to test during COVID and thinking about testing in general. So I guess this is not that unfamiliar for us. But especially when the management a lot of the time for the majority of people, for RSV is supportive, right? And it doesn't change.

That's exactly right. If someone presents with bronchiolitis, regardless of what the aetiology is, treatment is generally supportive. So oxygen for hypoxia, we're essentially using hydration to make sure particularly the babies who are unable to feed are getting adequately hydrated, and then there's ventilatory support in more severe cases. It is standard management for RSV, no magic drug unfortunately at this stage, but certainly there are preventative options available now.

Are there things in amongst RSV management that are distinctive compared to other infections or is it really just adding to the overall burden of seasonal viral infections?

I would say it would be just adding to the burden of everything. Yeah, there is nothing special about RSV in terms of treatment, but the preventative therapies are certainly a game changer.

It is an exciting time to have all these preventative options, but trying to find the right preventative measure for the right population, it can clearly get very confusing for people to get across. So can you give us a bit of an overview about the options that we have in terms of RSV prevention in different populations?

To start with, I think just in terms of an overview, in Australia we have 2 vaccines that are approved, and then we have monoclonal antibodies which are used in babies. The differences are, so with regards to vaccines, we have 2 products, Abrysvo and Arexvy. Abrysvo is a vaccine that's recommended for pregnant women between 28 to 36 weeks gestation, as well as adults who are over 60. And then a Arexvy specifically is for adults over 60. We strongly recommend vaccination for adults who are over 75 generally, but those who have risk factors or are Aboriginal or Torres Strait Islander descent, that's where that age lowers to 60. In terms of the pregnant women vaccine, this is actually currently funded under the National Immunisation Programme [NIP], which is really exciting.

And essentially what it does is it boosts maternal antibodies that cross the placenta and therefore protects infants for up to 6 months of age. What they found in the trials is that it actually reduced severe RSV disease by up to 82% at 3 months of age and 70% at 6 months of age. So quite effective in terms of that durable protection to get babies through that winter period. And then alternatively, for those babies who perhaps mum didn't receive the vaccine during that time or didn't have it at least 2 weeks before the baby was born, or those babies who have risk factors, essentially can get a monoclonal antibody. And so with this monoclonal antibody, in the past we used something called palivizumab, and this was a monthly injection that was given for 5 months. The new product on the block is nirsevimab and this is a long-acting monoclonal antibody for which the one dose actually provides 5 months worth of protection.

And this is fantastic because essentially babies can be given this monoclonal antibody at birth or within the first couple of days during their checkup and it is designed to protect them for that RSV season. The thing to note though is that also children who are vulnerable in terms of chronic medical conditions who are entering their second RSV season are also eligible to have the monoclonal antibody. And again, effectiveness-wise, early trial data showed that nirsevimab can be up to 70% protective against RSV, lower respiratory tract infection. So quite effective in terms of reducing those hospitalizations and severe outcomes.

So it's quite pleasing really that we've been able to try and cover babies, infants in that time when they're vulnerable from bronchiolitis, thinking about maternal vaccination and getting that passive chance of antibodies that are protective and then having monoclonal antibodies there as well. So now that maternal vaccinations is available on the NIP, is that right?

Yes, that's right. Exactly. So it's now funded for pregnant women, which is really exciting. And it can be given at the same time as the COVID vaccine or whooping cough vaccine or flu vaccine, which is an added bonus.

So in terms of the strategy of trying to reach this population, knowing that there's maternal vaccination, and then thinking about monoclonal antibodies, which are getting rolled out through states at the moment, trying to reach infants in that early stage, it must be really complicated to be able to get that information out and get those vaccines and preventative therapies out to the right people.

No, I definitely agree. I feel like there's a lot of education that needs to happen in terms of the community because as you mentioned earlier, not everyone has heard about RSV and so just to educate people about a virus that they've never heard of and then introduce the concept of another maternal vaccine where people are already quite hesitant during pregnancy to get any sort of vaccines or medications. And then again, to talk about a monoclonal antibody that's not just for high-risk kids because palivizumab essentially was just for high-risk, premature, chronic lung infants initially. I think there's a big effort in terms of being able to educate general public as well as clinicians, as well as anyone who encounter, particularly pregnant women. So a big initiative is talking to midwives, maternal child health nurses to make sure that, again, that messaging is really clear when it comes to speaking to women about vaccination of themselves and then nirsevimab potentially for their newborn infants if they don't receive vaccination.

Well, there's probably a lot of education and myth busting that needs to occur in terms of monoclonal antibodies in this setting in general. This is the first time that we've been doing this kind of thing on scale in this type of population. Despite experience with it during COVID, monoclonal antibodies, in different populations, to try and do this at this level must be really hard in terms of trying to reassure about administration and safety and what we are actually trying to achieve for infants.

Yeah. And I think this is where it's a big team effort. I think everyone needs to be involved in terms of all of the people within the healthcare system to support the messages and make sure that the correct information gets to people so that they can make informed decisions.

How have we seen this play out on the ground in terms of monoclonal antibodies in clinics? Are people quite accepting of it or do you think that there are concerns that get raised?

I think what we've found so far, and it is still early days, is that there are some people who are extremely keen and then those who are a little bit more reluctant and questioning the relevance of whether or not RSV is a significant virus? What the significance of monoclonal antibodies are, what the long-term effects are? And just the general hesitancy that comes with medicines and vaccine-type products. So it's been really interesting and early days. I think with more education, perhaps more people will understand the rationale for these products and hopefully be keen for them because it would be great to reduce those hospitalizations and see less babies admitted for RSV-associated bronchiolitis because it's a really big problem in our hospitals during winter.

So let's pivot a little bit to that older age population and how we look at RSV vaccination in that setting. So Abrysvo is also used in that setting, but then also we've got other options as well. How does that all sit in terms of the other vaccination programmes that are going on and trying to roll that out in that population?

Firstly, just to acknowledge that RSV can be as serious as flu in older adults. I think people forget that or don't realise that because, again, there's that education piece around the significance of RSV. And this is especially those who are over 75 or have chronic heart or lung disease. As you said, at the moment there are 2 RSV vaccines that are approved for adults over 60, which is Abrysvo and Arexvy. What we know is both of them have shown over 80% efficacy against lower respiratory tract infections and also up to 95% protection against severe disease in that first season after vaccination. The other thing to note is that at the moment there is no further data around booster vaccines for now and it's currently not funded under the National Immunisation Programme for this age group. So currently these vaccines are available privately. They can be given alongside the flu shot or the COVID shot as well. And it's worth anyone who's interested in this vaccine to have a chat with their GP or healthcare provider for more information.

So it seems like there's a lot to look forward to in this space as we get more and more access to vaccines. Do you think this is going to have an impact on the way in which we see seasonal respiratory viruses affect the broader population? But then I guess also thinking about those peaks that we see in terms of severe disease putting strains on hospitals.

I think this is what will evolve as we see the vaccine programme rollout. It's really important that we continue surveillance, which obviously we have a great National Surveillance Programme. And we know that when we introduce a vaccine and/or protective measures that there are changes in epidemiology. So let's see what happens. Hopefully we decrease burden of disease, hospitalizations and all of those things for not just the younger but also the older age groups.

It'll be fascinating to see how these new preventative measures can impact the real world impact of RSV. Thank you for your insights today.

Thank you. Thanks for having me.

Dr. Linny Phuong has no disclosures and I'm a member of the Drug Utilisation Sub-Committee of the Pharmaceutical Benefits Advisory Committee. I'm David Liew and thanks once again for joining us on the Australian Prescriber Podcast.