Influenza is an acute respiratory illness caused by a virus that can lead to complications in the respiratory system, including pneumonia, and major organ systems, including neurological complications, and in severe cases, death. It causes increased morbidity and mortality, especially in high-risk groups, including infants and young children, resulting in social and economic losses.

Among infants and young children, the risk of complications is high in children under five, and children over five are at high risk of spreading the disease to family members, making treatment and management of influenza essential.

Since introducing Tamiflu (oseltamivir phosphate), Roche Korea has provided effective treatment options for influenza patients in Korea and it introduced Xofluza (baloxavir marboxyl) lately. This novel antiviral stops the influenza virus from multiplying in just one oral dose.

Recently, the company also became the first in the world to launch a Xofluza suspension formulation for children over one year of age. This formulation is more convenient to take, providing effective treatment options for pediatric patients in the country.

Korea Biomedical Review met with Professor Kim Yoon-kyung of the Department of Pediatrics at Korea University Ansan Hospital to learn more about the changing patterns of influenza outbreaks since the Covid-19 pandemic, the risks of pediatric infections, and the benefits of Xofluza as an effective treatment management option.

Question: How has the Covid-19 pandemic changed influenza outbreaks?

Answer: First, let's take a look at influenza. Influenza is an infectious disease that occurs annually worldwide and is the only viral disease for which the World Health Organization (WHO) has consistently monitored infection trends since the 1940s. In Korea, the typical epidemic pattern starts in late November, usually during the winter months, peaks and declines until the following February, followed by another small peak around March or April.

While there is some regularity to the annual influenza epidemic, it is characterized by unpredictable variability in its scale, duration, strain, and magnitude. This is why it's important to get vaccinated every year.

During the pandemic, we have seen very few outbreaks of RSV and influenza, two respiratory viruses known to be highly contagious, due to increased social distancing and knowledge of personal hygiene. In the annual pandemics before Covid-19, there was a wide variation in the severity of symptoms from person to person -- some people were mildly ill and passed through, some people had the actual virus but didn't feel any symptoms and only increased immunogenicity, and some people were sick -- and there was an overall buildup of herd immunity.

However, with the lack of influenza during Covid-19, the opportunity to experience herd immunity has been lost. While influenza vaccination can provide some immunogenicity, it is not the same as that provided by natural infection. The vaccine also induces incomplete immunity, allowing people to acquire some natural infection but not get very sick. However, the absence of influenza in the past two years has led to a decline in overall immunity and the introduction of new viruses, especially in certain age groups of children (up to about two years old) who have never experienced influenza viruses.

With such low immunity, it's naturally more contagious when influenza returns. Each year, the Korea Disease Control and Prevention Agency (KDCA) and the Influenza Advisory Committee meet to set criteria and evaluate pandemic alerts. Last year and the year before, there was no pandemic alert termination due to the persistence of influenza throughout the year. We've been living with influenza for more than a year since the pandemic, as we've seen the alerts go off repeatedly. This year, we expect to see more of a pattern, but it takes time to reestablish itself once a pattern is disrupted. It took about two years to return to the normal cycle, even during the pandemic.

Q: Children up to age two have never been exposed to the influenza virus, so it will likely be difficult to predict their symptoms if they are infected.

A: At some point in their lives, everyone will encounter the influenza virus for the first time. However, the younger or older a person is at that time, the more severe the effects of the virus. Children are vaccinated against influenza, which directly or indirectly affects their immunogenicity, but in general, the younger they are, the less immunogenicity they get from the vaccine. Children are also at a higher risk of developing influenza complications, and these complications are more dangerous because they involve the heart and brain.

Korea is characterized by communal childcare for very young children. In general, when children under the age of three stay together for more than three to four hours, the risk of the common cold and its complications, such as purulent otitis media, increases sixfold. While this is not good from an infectious disease perspective, it's socially unavoidable as society needs co-parenting, which exposes children to pathogens at an early age.

Immunogenicity is not so bad if there are no complications (because they start learning about the disease early). However, suppose you're exposed to influenza when you're young. In that case, you're more susceptible to it because of your growing organs, so it's better (in terms of complications and other aspects) to get the same influenza when you're older and more immunogenic and able to fight it off than when you're too young. The good news is that there is a cure for influenza. Very few viruses that affect infants have a direct treatment, but we are fortunate to have a vaccine and a treatment for influenza.

Q: So, how is influenza treated in children?

A: Treatment is prescribed if a child tests positive for influenza using PCR or a simple antigen test. A diagnosis of influenza does not mean a prescription for treatment, but because children are at high risk, treatment can help bring down a fever faster and reduce the risk of complications.

Q: Tamiflu and its generics are already widely used to treat influenza in Koea. What makes Xofluza different from them?

A: The main difference is the duration of treatment. Tamiflu had to be taken over five days, whereas Xofluza only needs to be taken once, which is much better regarding availability. No matter how good a medicine is, it's useless if it's not taken.

Giving medication to children can be challenging, so flavor is important for any pediatric medication. In addition, pills are not always easy to give, even in the lower elementary school grades, and powdered medicines (depending on the medicine) can become soggy and clumpy in humidity, reducing their effectiveness.

It's great to be able to give kids syrup like Xofluza. From a medical point of view, I really appreciate that although the pediatric market is small, the drugmaker has considered how to make it easier for children to take.

Q: The safety profile of Xofluza must be very important as it is used in pediatrics.

A: Xofluza does not have major safety concerns. Still, it is difficult to define its safety profile because it is classified as a new drug, whereas Tamiflu, which has been used to treat influenza, has accumulated data for nearly 20 years. However, based on the data, the safety profile does not appear to be inferior to the alternative (Tamiflu).

Q: Is there caution when prescribing Xofluza at neighborhood clinics?

A: Xofluza is a new drug, so it's not cheap compared to other treatments. However, this is not a major concern since it is a single dose. There is also a single dose intravenous (IV) treatment for influenza, but it is covered by insurance and is already prescribed to many patients without difficulty. However, from a researcher's point of view, there is a problem because it is taken only once. Its long half-life means there is a risk of additional exposure to the virus in the interim, and the issue of resistance remains to be seen so that I would caution against overprescribing.

An effective treatment option like Xofluza should be kept around for a long time and used at the right time. To maximize its effectiveness, Xofluza should be administered within 48 hours of the onset of symptoms. Acting at a relatively early stage reduces the overall amount of virus and shortens the shedding period.

However, in healthy adults, it may take some time to get a diagnosis of influenza because they may not come to the doctor right away. I think it desirable to maximize the effectiveness of early diagnosis and early administration of Xofluza in high-risk children and older adults, as the earlier, the better.