By Ethan Covey
During what the CDC is calling the worst flu season since 2017-2018, 13% of children who have died of influenza had influenza-associated encephalopathy or encephalitis (IAE), a severe neurologic complication.
As of Feb. 8, 2025, IAE was identified in nine of 68 children who died from influenza. This includes four children who were diagnosed with acute necrotizing encephalopathy (ANE) (MMWR Morb Mortal Wkly Rep 2025;74[6]:91-95). All of the ANE deaths were in children younger than 5 years of age with laboratory-confirmed influenza A(H1N1)pdm09, only one of whom had underlying medical conditions.
While the authors of the report wrote that it is not known whether cases observed in the 2024-2025 season vary from expected numbers, data from the Influenza-Associated Pediatric Mortality Surveillance System provide indications of higher numbers; the median proportion of pediatric influenza deaths with IAE was 9% from the 2010-2011 to 2024-2025 flu seasons. Currently, no national surveillance for IAE exists in the United States.
“We know that flu can cause encephalopathy, but this appears to be more prominent than we’ve been aware of in the past,” William Schaffner, MD, a professor of preventive medicine, Department of Health Policy, and professor of medicine, Division of Infectious Diseases, at Vanderbilt University, in Nashville, Tenn., told Infectious Disease Special Edition.
“These findings are provocative, and sad,” Dr. Schaffner added. He noted that, while these preliminary data could end up being a statistical aberration, research is needed to better understand why IAE can occur in normally healthy children.
The deaths have come during a particularly brutal influenza season, according to the CDC. While levels of flu appear to have peaked during the week of Feb. 8, seasonal influenza activity remains elevated across the country. The CDC has now classified the 2024-2025 flu season as a “high-severity” season for all age groups, the first high-severity season since 2017-2018.
Overall, U.S. influenza infections during the 2024-2025 season are at or near the highest levels seen in 15 years. To date, there have been an estimated 33 million illnesses, 430,000 hospitalizations and 19,000 deaths from flu.
“We have had a very serious influenza season,” Dr. Schaffner said. “It’s starting to nose down, but it has been the worst season in many years.”
Most cases have been caused by influenza A virus. Among the 1,788 influenza A viruses that were subtyped during the week ending Feb. 15, 62.4% were influenza A(H1N1)pdm09—the one that caused the IAE deaths—and 37.6% were A(H3N2).
Thankfully, interim vaccine effectiveness (VE) data released by the CDC show the current influenza vaccine has been effective at significantly reducing doctor visits and hospitalizations during the 2024-2025 flu season among those who are vaccinated (MMWR Morb Mortal Wkly Rep 2025;74[6]:83-90).
Data from the report show that children who received the influenza vaccine were 32% to 60% less likely to visit a doctor with flu-related symptoms, and 63% to 78% less likely to be hospitalized. Adults who received a flu shot were 36% to 54% less likely to visit a doctor because of influenza, and 41% to 55% less likely to be hospitalized.
However, vaccination is down among many groups, including children, according to the CDC. As of Feb. 15, an estimated 45.8% of children received a flu vaccination, lower than last season at this same time (50.9%). As of Feb. 15, 45.3% of adults received a flu vaccination, similar to last season at this same time (45.3%). However, vaccination was higher among adults who were 65 and older. Vaccination was lower among Hispanic and Black adults of all ages, according to the CDC.
As of Feb. 1, an estimated 36.5 million doses of flu vaccine were administered in retail pharmacies. This was about 702,000 fewer doses than were administered by this same time during the 2023-2024 flu season, and an estimated 20.6 million doses were administered in physicians’ medical offices. This was about 4.2 million fewer doses than were administered by this same time point in the 2023-2024 flu season. The CDC said there could a lag in claims processing, which is why these numbers are not final.
In contrast to influenza, both COVID-19 and respiratory syncytial virus (RSV) have yet to cause significant outbreaks during the 2024-2025 season, according to the CDC.
While COVID-19 activity is elevated in many areas of the country, a large winter COVID-19 surge has not materialized. During the fall and winter respiratory virus season, peak hospital demand due to COVID-19 was lower than in all previous seasons, and nearly 50% lower than during last season’s peak. RSV activity remains elevated but is declining in most areas of the country.
“While we had an increase in COVID-19 this winter, it was fortunately less than expected and less than we saw last summer,” Dr. Schaffner said. “RSV came in a bit late, and appears now to be topping out.”
CDC data on the VE of the existing COVID-19 vaccine show that, much like the flu vaccine, it has been helpful in averting hospital visits and related hospitalizations (MMWR Morb Mortal Wkly Rep 2025;74[6]:73-82).
Among adults 18 and older, the VE of the 2024-2025 COVID-19 vaccine was 33% against COVID-19–associated emergency department or urgent care visits, and 45% to 46% against hospitalizations among immunocompetent adults 65 and older, compared with not receiving a COVID-19 vaccine. In addition, the VE against hospitalizations was 40% in immunocompromised adults 65 and older.
“The best modern science can’t yet give us vaccines that can prevent each and every case of these illnesses,” Dr. Schaffner said. “But what they do best is prevent serious disease and deaths. And clearly, these vaccines have performed well in this regard.”
