Reference:  Drysdale SB et al. Nirsevimab for Prevention of Hospitalizations due to RSV in Infants. N Engl J Med. 2023 Date: March 29, 2024 Guest Skeptic: Dr. Michael Cosimini is a pediatrician in Portland Oregon. He is the designer of Empiric Game, a medical editor and contributor to Pediatrics Reviews and Perspectives (PedsRAP) and the digital media editor at Academic Pediatrics. He is passionate about podcasting and serious games for medical education. Dr. Michael Cosimini Case: A 4-month-old twin girl is brought by her parents to the emergency department (ED) for respiratory distress. She has had congestion, a runny nose, and a cough for the past three days. Her parents think her breathing has been getting worse, and she is breathing faster. On your examination, you see that she is tachypneic with a respiratory rate of 66 breaths per minute. You also note subcostal retractions. Her oxygen saturation on room air is 86%. After nasal suctioning, she remains tachypneic, but her oxygen saturation remains under 90%. A viral swab comes back positive for respiratory syncytial virus (RSV). The decision is made to put her on supplemental oxygen via nasal cannula and admit her to the hospital for close observation. Her parents tell you, “She has a twin brother at home. We heard about this new vaccine for RSV. Does it work?” Background: RSV is a major cause of respiratory illness in young children. It is common in bronchiolitis which leads to symptoms like coughing, wheezing, and difficulty breathing. RSV is a major reason why infants are hospitalized for respiratory issues, especially during the fall and winter months when RSV infections are more prevalent.  It's hard to think about RSV without recalling the quote “Don’t just do something, stand there!” Because there have been so many things that we’ve tried for bronchiolitis that really don’t seem to have had much effect including hypertonic saline (SGEM#157), high-flow nasal oxygen (SGEM#228), corticosteroids, bronchodilators, etc  (SGEM#167).  One thing that has also been tried but not covered on the SGEM is a "vaccine" for RSV.  Attempts at developing a vaccine against RSV go back decades. The first significant effort to develop an RSV vaccine occurred in the 1960s. A formalin-inactivated RSV vaccine (FI-RSV) was developed and tested in infants and young children. However, instead of protecting against RSV, the vaccine led to worsened infection in many children resulting in some being hospitalized and two deaths. This tragic outcome slowed the development of an RSV vaccine for years. Over the next three decades, researchers sought to understand the immune response to RSV infections and explore potential vaccine targets other than the inactivated virus. During the 2000s, advances in molecular biology, immunology, and vaccine technology rekindled scientists’ efforts in RSV vaccine development. Researchers began exploring various approaches, including protein subunit vaccines, vectored vaccines, live-attenuated vaccines, and mRNA vaccines. Over the last decade, several RSV vaccine candidates have entered clinical trials. These trials have included vaccines for infants, older children, and at-risk adults, such as the elderly and pregnant women (intending to provide passive immunity to newborns). While some RSV vaccine candidates have shown promise, the challenge has been to find a vaccine that is safe, effective, and can provide long-lasting immunity. In 2022 in the European Union and UK and 2023 in the US and Canada approved Nirsevimab to prevent RSV. This is a monoclonal antibody that is supposed to neutralize RSV. Nirsevimab specifically targets a protein that is critical for the virus’s ability to enter and infect human cells, thereby stopping the disease process in its tracks. This action does not rely on the recipient's immune system to activate or produce antibodies, providing immediate protection. This new vaccine technology represents a shift to...