[Automatically generated] From the JAMA Network, this is JAMA Clinical Reviews, interviews and ideas about innovations in medicine, science and clinical practice. Here's your host. Hello, I'm Dr. Kristin Walter, Deputy Editor at JAMA. I'm joined today by Dr. Kathleen Linder, an infectious disease physician and clinical assistant professor of medicine at Michigan Medicine. Today, we will be discussing an insights article that Dr. Linder recently co-authored with Dr. Scruggs-Wodkowski and Dr. Preeti Malani, titled, Therapies to Decrease Severe Respiratory Sensitial Virus, RSV, Illness. Welcome, Dr. Linder. Thank you for having me, Dr. Walter. So, RSV is a common cause of acute lower respiratory infections, especially in children who are younger than age two. Can you describe the typical course of RSV infection for healthy children and healthy adults under age 65? Absolutely. In most children, RSV presents similarly to a common cold. Children may have fevers or other respiratory symptoms, they may have a cough or stuffy nose, and they may just not feel like themselves. The same applies to adults who may catch that virus from their children. And which children and adults are at highest risk of developing severe RSV infections? People who are at the highest risk of developing RSV infections are children under the age of two, primarily those who are born prematurely, or older adults above the age of 60, who also have other chronic medical conditions, like heart disease, lung disease, or immunocompromised for whatever reason. Approximately how many children and adults in the US are hospitalized annually due to RSV infection and how many die? So every year, RSV leads to between 58,000 and 80,000 hospitalizations in children and unfortunately between 100 to 300 deaths per year. In adults who are greater than the age of 65, RSV causes 60 to 160,000 hospitalizations and 6 to 10,000 deaths per year. Currently, there are two therapies to decrease the risk of RSV infection in infants and children. One is monoclonal antibodies and the other is maternal RSV vaccination during pregnancy. Let's start by discussing the monoclonal antibody, Valumizumab. Can you explain how long this treatment has been available and how it is administered? Absolutely. Valumizumab is an antibody that binds to the RSV fusion protein and makes the virus unable to infect further cells. It's been available in the United States since 1998 when it was approved by the FDA. And how is it given? Valumizumab is given as an intramuscular injection and it's given monthly for a total of five months. And which infants and children are currently recommended to receive Valumizumab? Right now, Valumizumab is recommended for children and infants born earlier than 29 weeks, who are at the beginning of an RSV season, that is in September in the Northern Hemisphere and March in the Southern Hemisphere, or to children who are born before 29 weeks, who have chronic lung disease or congenital heart disease, or it can be considered in children who have other anatomic issues or are immunocompromised for whatever reason. And when you're talking about anatomic, are you referring to cardiac? Often this is things like tracheobronchomalacia and other pulmonary issues. And how effective is Valumizumab in decreasing rates of severe RSV infection in these children? Valumizumab is quite effective, and it reduces risk of severe RSV by 55% in the 150 days following the first dose. Let's move on to the other currently available RSV monoclonal antibody, Nercevimab, which received US FDA approval in July 2023. Which children are recommended to receive it, and how often is this therapy administered? So Nercevimab is also an intramuscular injection, but because of its long half-life, it can be given once per RSV season. This actually was recommended for all infants who are below the age of eight months at the beginning of the RSV season, as long as their birthing parent had not been vaccinated against RSV. This led to a lot of children being candidates for Nercevimab injections in the last year. And how effective is this drug in decreasing rates of severe RSV infection? The Nercevimab is a little bit more effective than Pallivizumab, with an effectiveness of 79.5% in preventing severe RSV in the 150 days following the dose. And in October 2023, the CDC announced that there was limited availability of Nercevimab. What are the updated recommendations about who should get this treatment during this shortage? As of right now, the CDC continues to recommend Nercevimab for children who are below the age of eight months at the beginning of the season. However, this can be avoided if the child's birthing parent is vaccinated against RSV during pregnancy. And the CDC specifies that children who are able to receive Pallivizumab should receive that instead of Nercevimab. Additionally, the CDC does not recommend additional doses of Nercevimab, except in a few cases. At this time, the CDC only recommends a second dose or a dose after the age of eight months in children with chronic lung disease, severe immunocompromised or severe cystic fibrosis. Additionally, it recommends an extra dose in children who are of American Indian or Alaska Native background due to systemic inequalities in health care in those communities. And how far apart if people are getting two doses, if children are getting two doses, how far apart would that be administered? So they would get their first dose at the beginning of their RSV season and then a second dose at the beginning of a second season. Okay, so a total of two doses at maximum. That's correct. And again, children should only get the second dose in certain circumstances. The other way to protect infants from RSV is through vaccination during pregnancy, as you mentioned. Can you discuss the RSV vaccine that has been approved by the FDA for pregnant individuals? So the RSV vaccine, Abrisvo, which is a Pfizer vaccine, has been approved for pregnant people in the United States after 32 weeks of gestation and in Europe after 24 weeks of gestation. This vaccine was 82% effective in preventing severe RSV disease in the subsequent infant in the first 90 days of life and 70% effective in the first six months of life. This is the only RSV vaccine that's approved in pregnancy. Is that correct? That's correct. At this time, while there are two vaccines available for older adults, only the Abrisvo vaccine is approved for use in pregnancy. Shifting to older adults, which for this discussion is defined as age 60 or older, there are two vaccines that are currently available. Can you discuss these vaccines? Both vaccines work in a similar way to block the pre-F fusion protein and make it so that RSV is unable to enter the cell for further infection. These vaccines are both protein-based and are called Abrisvo and OREXV. What is the evidence about their efficacy in preventing RSV lower respiratory illness? Let me go one vaccine at a time. Abrisvo, which is a Pfizer product, was shown to be 67% effective in preventing RSV with two symptoms and 86% in preventing RSV with three or more symptoms. It was 62% effective in preventing any RSV infection. However, the population in the study was primarily a healthy population. Most patients were not immunosuppressed. Similarly, a RexV, which is a GSK vaccine, was 83% effective in preventing lower respiratory tract infection from RSV and 94% effective in preventing severe lower respiratory infection from RSV. It was 72% effective in preventing any RSV infection in the adults studied. Immunocompromised people were not included in this study. So what are the current CDC recommendations about RSV vaccination for adults to age 60 years and older? At this time, the CDC recommends shared decision making between a primary care provider and the patient to determine whether or not the patient is a candidate for any RSV vaccination. Shared decision making should include a discussion of the best available evidence of whether or not the patient would benefit from vaccine and should take into account the individual patient's characteristics, values and preferences. And can you discuss any adverse events associated with these RSV vaccines? A Breezeville was relatively well tolerated, although there were two cases of Guillain-Barre syndrome reported in the cohort of vaccinated people. While those two cases are concerning, it should be noted that the cohort included over 30,000 patients, and so the overall risk of Guillain-Barre syndrome remains low. A RxV is also well tolerated, but does have a higher rate of injection site reactions. This is probably because this is an adjuvanted vaccine, and so almost 60% of patients who received this vaccine in the clinical trial did note some degree of injection site reaction. Which would be what, swelling and erythema? Yep, typically that presents as swelling, erythema, and pain at the site of the injection. Most patients had a mild or mild to moderate reaction, and this improved without any medical attention. Additionally, while there weren't any cases of Guillain-Barre syndrome reported in the large Phase III clinical trial, there have been a few cases of Guillain-Barre syndrome reported in some other smaller studies, and so this is being further investigated. Before closing, is there anything else you'd like to mention that we haven't previously discussed? I think it's really important to note that these vaccines are not only preventing severe RSV, but also the complications that come with RSV infections and RSV infection. There's been a lot of really great work that's come out over the past few months to really suggest that the severity of RSV, particularly in older adults, may be higher than what had previously been noted. One recent study showed that about 20% of adults who were hospitalized with RSV had a subsequent cardiac event. There's also been research that suggests that RSV complications may be more numerous than complications from influenza, which are well recognized. I think it's important that providers have a discussion with their patient population to decide whether or not getting this vaccine is right for them. Thank you so much for sharing your thoughts with us about this interesting and important topic. That was Dr. Kathleen Linder from Michigan Medicine, and I'm Dr. Kristin Walter. To follow this and other JAMA Network podcasts, please visit us online at jamanetworkaudio.com. Thanks for listening. This episode was produced by Shelley Steffens at the JAMA Network. Thank you for watching.