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.