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Forest W. Arnold, DO, MSc: Hello I'm Dr Forest Arnold, and welcome to Medscape's InDiscussion series on respiratory syncytial virus (RSV) in adults. Today we'll be discussing (RSV) from the perspective where most of us have our landmark knowledge, which is in infants, to build a base as we discuss RSV in adults in future episodes.

Dr Statler is currently an assistant professor in infectious diseases at the University of Louisville and the director of the pediatric transplant and immunocompromised host service at Norton Children's Hospital. Welcome to InDiscussion.

Victoria A. Statler, MD, MSc: Thank you, Dr. Arnold. I appreciate the invitation to speak today.

Arnold: Great. I would like to start with a case. Consider a 3-month-old who's brought to the emergency room (ER) with a 3-day history of rhinorrhea, congestion, and cough. A fever started today, which prompted the ER visit. On exam, the infant has wheezing bilaterally. A nurse performs nasal suctioning and checks the pulse oximetry.

I ask you, Dr Statler, what is your approach to this patient and what happens next in the workup of this infant?

Statler: This infant's presentation is very typical of many infants and young children coming to our ER in the fall and winter of most years. It seems like this child has started with an upper respiratory tract infection that sounds like it has probably gone into the lower respiratory tract, since you have wheezing on exam. Our initial assessment is to see if the patient is in a lot of distress and try to gauge how much distress the patient may be in, and then to look at the pulse oximetry and see if the infant is getting adequate oxygenation.

From there, we do our basic physical exam, including listening to the infant. This sounds like patient with bronchiolitis to me just in your description, and usually the patient with bronchiolitis on auscultation will have diffuse wheezing. You may hear some diffuse crackles and rales, and they'll have a prolonged expiratory phase as well. When you first look at them, there may be nasal flaring. They may be having accessory muscle use. You may see subcostal or supersternal retractions. Those are all clues that help gauge how sick the infant is.

Arnold: This past season for RSV was incredible. I think we're all familiar with how severe it was, and I'm interested in what aspects of the season stood out to you.

Statler: Before the COVID-19 pandemic in early 2020, most RSV seasons were pretty typical. You kind of knew when they were going to start, you knew when the number of infections were going to peak, and you sort of knew when it was going to fade out. Now, there was, of course, some regional variation in the United States, but typically a season would start in the late fall. Usually you would start to see cases trickle in in mid- to late September, and then a peak in late December to mid-February. By the time spring rolled around in most temperate climates, you would see much less circulation of RSV.

This year, we saw RSV really start to tick up in August and September and peak in November. It came in with a vengeance this year. We saw a lot of patients in a very short time period and had a much higher hospitalization rate this season than we have in the past. It's interesting because the COVID 19 pandemic disrupted the circulation of RSV and other common respiratory viruses. After COVID came around in March 2020, that following fall and winter, we didn't see the typical RSV and flu season. We started to see some RSV early in 2021 and had an uptick in the spring months of 2021. It peaked in July that year, which was completely abnormal and atypical for an RSV season. We're not quite back to the typical circulation of the respiratory viruses after the pandemic yet.

Arnold: When we enjoyed that RSV flatline in 2020 and 2021, that means there was a whole group of people out there, especially children, who did not develop antibodies because they were not infected. It's almost like the next season it was just loading up for more people. Do you think that contributed to the larger season we had this past year?

Statler: I think that's a great hypothesis, and we've talked about that locally with some of my colleagues. We have this whole group of children who were born in the midst of the pandemic, who didn't have the typical exposures in their first year of life, because we did not see a lot of the common respiratory viruses.

Arnold: I have in front of me a figure from the Centers for Disease Control and Prevention (CDC) that outlines the past five seasons for RSV. It shows the hospitalized cases per 100,000 population. What we see is that each year and if you look back at 2018-2019, the season peaked about the end of February, but each subsequent year it was a little higher and a little sooner. The exception is the 2021 season; that was flatline. By the time you get to this year, as you said, it peaked in the end of November. So, it was February, then January, then December and now November. What are your comments about how this has played out?

Statler: It really took us by surprise this year. After the summer surge the year before, we weren't sure what to expect with the RSV season this year. I think we actually saw co-circulation of SARS-CoV-2 and flu during that time. We had quite the surge in our hospitalizations and in our ER visits. If you look at the number of hospitalizations in children under 5 for this past season, at its peak it was almost 64 per 100,000. Those are the most recent numbers that the CDC has put out on RSV-NET. And that's significantly higher than it has been in previous typical seasons.

Arnold: When we think about the child that was presented at the beginning, what diagnostics do we have for RSV?

Statler: It's interesting that you ask that. Before the pandemic, we often didn't have to use a diagnostic test if it was the middle of November or December and a child came in with wheezing and symptoms that were consistent with bronchiolitis. You could make that diagnosis on history and physical alone. You knew it was RSV season, it was probably RSV causing that episode of bronchiolitis in that child, especially if they were in their first year of life. Now, because of the atypical season and circulation that we've been seeing, we tend to use RT-PCR on a nasal swab. The ones that we've been using locally have flu and SARS-CoV-2 on them. We get to see three different viruses with one swab. We also have a multiplex PCR panel, which is a respiratory pathogen panel that has 16 or 17 other viruses and some bacteria on it as well. We don't tend to use that as frequently, although I will use that in my immunocompromised hosts, because it's important for us to know if there's a different virus there.

Arnold: On the adult side, that is exactly how we approach the patients, especially every year there's an epidemic of influenza. We don't rely on a test per se. Our diagnosis is our history and physical exam. That's consistent.

We can't escape without talking about treatment. This may be a short conversation, but tell us about treatment for RSV.

Statler: There is no specific pharmacologic treatment that we use for RSV in children. The mainstay of therapy is supportive care. It's important to assess their oxygenation status. Checking pulse oximetry is important and giving them supplemental oxygen as needed. We usually give that via nasal cannula. It's usually a humidified oxygen source for those patients. We assess by taking a pulse ox reading and seeing if they have consistent desaturations < 90%. If they do, then we give them humidified oxygen, usually an inpatient setting.

The other things we assess are their hydration and feeding status. Some of these infants who are breathing really hard can't eat. Some of these patients will be admitted for intravenous fluids or for nasogastric feeding if they're unable to feed on their own.

Beyond that, there is suctioning. At home and in the outpatient setting, you can use bulb suctioning. These infants tend to have a lot of mucus production, and suctioning the nose and the mouth helps that a lot. In the hospital, we can do nasopharyngeal suctioning as well, which is a little bit deeper suctioning that helps some of the more severely ill infants that end up needing hospitalization.

Arnold: Up to this point, we've seen how severe this season is, with a peak of 64 hospitalizations per 100,000 population. We also see the treatment is supportive care, which includes suction, hydration, and supplemental oxygen, leading to an emphasis on prophylaxis of RSV. Can you discuss that for us, Dr Statler?

Statler: As you know, we do not have a routine vaccine for RSV, although I am excited about what is probably on the horizon for children and adults, too. We currently have a passive prophylaxis product called palivizumab. It is a humanized immunoglobulin G monoclonal antibody that binds to the conserved site on the RSV virus — the F protein that is on the viral surface and usually has to undergo a confirmational change in order to bind to the respiratory epithelial cells in the host. Palivizumab is a passively given antibody product to high-risk infants, and that monoclonal antibody binds to that F protein before it can make that conformational change, preventing the virus from being able to bind to our respiratory epithelial cell and getting into the lungs and replicating. We do have that in our arsenal.

The American Academy of Pediatrics (AAP) has put out guidance for who they recommend that that product be used for. At this point in time, we do not give it to all infants. It is recommended for only a selected group that are at the highest risk for severe RSV disease. According to the AAP guidance, this is infants who are born at less than 29 weeks' gestational age and are in their first year of life and their first RSV season.

The other recommendation is for infants who have chronic lung disease of prematurity, meaning that they were born at less than 32 weeks' gestational age and require supplemental oxygen for the first 28 days of life. If those infants are in their first year of life, they qualify for palivizumab prophylaxis as well. Those same children, those same infants in their second year of life, if they are still require medical therapy or medical support for their chronic lung disease in the 6 months leading up to RSV season, they may also qualify for palivizumab prophylaxis.

There are a couple of other groups that are near and dear to my heart. We also give palivizumab prophylaxis to children who are under 2 years of age and are severely immunocompromised. That includes our heart transplant recipients, and infants who are in their first year of life who have hemodynamically significant heart disease, airway abnormalities, or a neuromuscular disorder that may impair their cough. It should be considered for those children as well.

Arnold: It sounds like those who are less than 29 weeks and in their first RSV season. This may include infants who have chronic lung disease and those infants with chronic lung disease, who may still be a candidate in their second year of life. And then you have another group of people who are less than 2 years of age who are immunocompromised or have specific comorbidities.

Statler: Correct.

Arnold: Is there other discussion about palivizumab that you need to share?

Statler: Palivizumab is one of those things that these infants will get each month during RSV season, usually a maximum of five doses. Again, prior to the pandemic, they would start to get their palivizumab in October or November and go through March or April of the same year. The AAP has put out guidance for this past season and for our current season that because of the unusual and atypical seasons we've had since the pandemic. There may be some infants who end up getting more than five doses because the RSV season has started earlier, and we weren't sure how long it was going to go. Some of these infants may end up getting more than five doses.

Arnold: Fortunately, this season radically increased as it went, but seemed to drop off just as quickly.

Statler: Thankfully, we have not seen as many cases here in late March.

Arnold: We heard of the concept of "flattening the curve" with COVID-19. If you flatten the curve, you will have more resources in the hospital. RSV did not afford us that opportunity. Without a vaccine, there weren't many efforts to flatten the curve and spread those infants over the whole season to make it easier on the healthcare providers taking care of these infants. Would you agree?

Statler: We saw a lot of patients in a very short period of time this past late fall.

Arnold: Exactly. We all know that antibiotics are not indicated for viruses, but is there a role for antibiotics with RSV?

Statler: In general, antibiotics are not indicated for infants with RSV. First of all, it's pretty rare that these children will have a superbacterial infection along with their RSV. Some younger infants who may also have fever may get additional workup. It is rare to see bacteremia or some other serious bacterial infection. Occasionally you will have some patients who have acute otitis media. Typical antibiotics for the treatment of acute otitis media may be indicated in those cases. For RSV bronchiolitis, they are not indicated. There's not a lot of pharmacologic products that we can use in RSV bronchiolitis. Even bronchodilators have not shown consistent clinical benefit. Steroids have been looked at as well and have not shown any consistent clinical benefit for the treatment of RSV in children.

Arnold: You mentioned co-infections, which makes me think also of viral co-infections. The short viral diagnostic test has flu, COVID, and RSV on it. I wonder if you've seen this season children or infants who did have RSV and flu or RSV and COVID.

Statler: That's an interesting question. I personally, anecdotally, have not seen those particular co-infections. Now I have seen RSV with rhinovirus. On that more extended multiplex PCR panel that we have, I have seen a few of those co-infections. I can't think of any off the top of my head that have had both RSV and COVID or RSV and flu, although I'm sure that probably occurred this season.

Arnold: You would think these infants would be so susceptible to COVID-19. Talk about a novel infection; they're a novel human. They really have not seen it, unless maybe they have some maternal antibodies. When we had our flatline of RSV during that season of 2020/2021, I think it spoke to how contagious COVID-19 was because it was still peaking in the midst of these other viruses not peaking. I would still expect maybe in the next seasons to see viral co-infections, but we'll just have to wait and see.

Statler: It's interesting, because I thought the same thing. All we saw was SARS-CoV-2 that year, and we really saw nothing else. We did a lot of nonpharmacologic interventions like masking and physical distancing. Yet somehow, although it helped maybe curb the SARS-CoV-2 circulation, it didn't stop it altogether, but it seemed to really stop and have an effect on a lot of the other viruses. Obviously, that's hypothesis, and perhaps it was SARS-CoV-2 itself and its interaction with other viruses that may have made that happen. But obviously we don't have a lot of data on why we saw what we saw at that time.

Arnold: Speaking from your role as an infectious diseases doctor who works with transplant patients, how does RSV affect the donor-recipient transaction?

Statler: If we have a child who is clinically symptomatic waiting for an organ transplant, most times we will delay that transplant until they're able to recover from their RSV. We don't want to immune-compromise children who have an RSV infection and put them through a major surgery.

Arnold: Finally, for those infants in children's in the hospital with RSV, we need to clarify that isolation is required. Interestingly, the CDC has contact and standard precautions. Certainly, any hospital makes up their own rules, but they probably at least do that or more. What is your experience?

Statler: We use contact and standard precautions, and we also do droplet precautions. These babies are coughing, and you're in their face suctioning them. Having masks and goggles on for a lot of these interactions is important.

Arnold: I think droplet isolation makes common sense as well.

Today we've had Dr Statler discussing RSV and pediatrics to shore up our knowledge base about this important topic before we move into adults. RSV for this past season was associated with increased hospitalizations and increased mortality subsequently without significant treatment other than supportive care. There's an emphasis on prophylaxis and specific indications for palivizumab. Thank you so much for joining us. This is Forest Arnold for InDiscussion.


CDC RSV National Trends


Palivizumab for the Prevention of Respiratory Syncytial Virus Infection

Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins

Updated Guidance: Use of Palivizumab Prophylaxis to Prevent Hospitalization From Severe Respiratory Syncytial Virus Infection During the 2022-2023 RSV Season

Type and Duration of Precautions Recommended for Selected Infections and Conditions

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