Keeping the Focus on Influenza Viruses: A Challenge, to Say the Least

“The current circulating influenza A (H3N2) virus acquired seven new mutations over the summer, which means the virus is quite different to the A (H3N2) strain included in this year’s vaccine.”

Antonio Ho, MD, University of Glasgow, Glasgow, Scotland

“The United States may be headed for a rough flu season, with a virus that causes more severe symptoms than the one last year and seems to be spreading more rapidly and earlier than usual.”

Apoorva Mandavilli, American investigative journalist, New York Times

As we celebrate Thanksgiving tomorrow, there’s an unwanted “guest” we all hope won’t show up at our gatherings—the influenza virus, the cause of the highly contagious respiratory infection commonly referred to as “the flu.” In this week’s Germ Gems post, I provide a brief overview of the three types of flu viruses we need to keep our eyes on: seasonal influenza viruses, avian influenza viruses, and pandemic influenza viruses.

Influenza virus classification. Influenza viruses are mRNA viruses. There are four major types of influenza viruses: A, B, C, and D. The virus is classified by its surface proteins: hemagglutinin (HA) and neuraminidase (NA). There are 18 known HA and 11 known NA subtypes in total, most of which are found in flu viruses that infect birds.

The influenza A group of viruses are by far the most important in human infections. They have a high morbidity and mortality causing millions of illnesses and up to 650,000 deaths globally each year. They are highly contagious spreading easily from person to person through respiratory droplets from coughing, sneezing, and talking. They have the ability to constantly evolve (genetic malleability) allowing them to evade existing immunity and requiring annual vaccine updates. And, they can infect a wide range of animal species (including birds, pigs, and humans).

Seasonal flu. Nationally, the 2024-2025 influenza season was considered the nastiest flu season (hospitalizations and deaths) in more than a decade. (Morbidity and Mortality Reports, September 25, 2025). It was characterized by the co-circulation of influenza A(H1N1) and A(H3N2) viruses. Influenza A (H3N2) is circulating in the current 2025-2026 flu season, and many experts are concerned that this flu season will be worse than the last.

Influenza A (H3N2) causes more severe symptoms than the viruses circulating last year. It also seems to be spreading more rapidly and earlier. And the emergence of at least seven seasonal influenza A (H3N2) variants allow this virus to sidestep immunity against infection. (Sabaiduc, S., et al., “Emergence of seasonal influenza A(H3N2) variants with immune escape potential warrants enhanced molecular and epidemiological surveillance for 2025-2026 season,” Journal of the Association of Medical Microbiology and Infectious Disease Canada, October 31, 2025; Spiete, H., “New Flu Strain Poised for Possible Takeover,” Medscape Medical News, November 14, 2025; Mandavilli, A, “Early Signs Point to a Harsh Flu Season in the U.S.,” New York Times, November 19, 2025).

Even though the influenza virus now circulating is quite different from the A(H3N2) strain included in this year’s vaccine, getting vaccinated for the flu this season is still recommended as it will help prevent the most severe sequelae of the flu, including hospitalization and death.

The American College of Physicians recommends that everyone aged 18 to 64 years who is not pregnant or immunocompromised should receive the influenza vaccine for the 2025-2026 season. The American College of Pediatrics recommends annual influenza vaccination of all children without medical complications starting at 6 months of age. (Last year, 279 children in the U.S. died from influenza or influenza-associated complications about 80% of whom were unvaccinated.) To make your final decision, consult with your physician or healthcare provider.

Bird flu.  Bird flu is caused by avian influenza A usually spread between birds, not people. One subtype of bird flu caused by influenza A (H5N1) has been spreading worldwide in wild birds, U.S. poultry, and cows as well as a growing number of mammal species. The consequences for these animals is devastating. (See, e.g., “Should H5N1 Influenza [“Bird Flu”] Be Treated Like a Pandemic?,” Germ Gems,  March 26, 2025).

We need to keep a close eye on this influenza virus as it is having a resounding impact on many animals we love. Equally important is the constant worry it could develop a genetic change allowing it to jump from human to human. ( O’Mary, L., “Bird Flu Is On the Rise Again. What Physicians Need to Know,” Medscape Medical News, November 11, 2025).

Pandemic Influenza. Gene-swaps between species have played a role in at least three of the last four flu pandemics. They are very important in the infection of mammals by bird (avian) flu. Three of the four influenza A viruses that caused pandemics in humans (H1N1, H2N2, and H3N3) started as avian flu in birds: 1918 (“Spanish Flu” ), 1957 (“Asian Flu”), and 1968 (“Hong Kong Flu”). (The 2009 pandemic was also caused by an H1N1 subtype, but it was linked to swine.)

As of this writing, 71 cases of influenza A (H5N1) had jumped from birds or cattle into humans. Fortunately in most cases, they caused only mild illness in the humans. (Only one death has been reported as of November 14, 2025.)

On October 29, 2025, a new case of avian flu in a human caused by influenza A (H5N5), a rare strain of the bird flu never seen in humans before, was reported from Gray Harbor County, Washington.  On November 22, 2025, this patient died. 

To date, there have been no cases of human to human transmission of the avian flu. Numerous influenza virus scientists are, however, working on trying to understand what allows the virus to be spread from human to human. This is a key step in understanding what could trigger the next pandemic. (Pappas, S. “What Would It Take for Bird Flu to Spread among Humans?,” Scientific American, July 15, 2025).

Whether we want to believe it or not, there will be another pandemic. Therefore, funding research on the flu virus and, for that matter, on all aspects of influenza biology, prevention, and treatment should be a high priority for the U.S. government. Unfortunately for all of us,  it appears that government funding for scientific and medical research that could prevent the next pandemic is not even on this administration’s radar screen.