Emerging H5N1 mutations raise risk of human infections

Avian influenza, commonly known as bird flu, is a viral infection primarily affecting birds. A global outbreak of H5N1, a highly pathogenic avian influenza virus, has been spreading across the world since late 2020, driven by a new emerging lineage of the virus — 2.3.4.4b. H5N1 has been a significant concern in global public health due to its potential to cause severe disease in humans and its ability to infect a wide range of hosts, including poultry, wild birds, and mammals. Since its emergence in the late 1990s, the virus has predominantly been an issue for the poultry industry, but sporadic human cases have raised alarms about its pandemic potential. However, recent human cases of H5N1 in British Columbia in Canada and California have increased concerns about the adaptability of the virus and possible mutations that could facilitate human-to-human transmission.

In November 2024, a teenager from Fraser Health, British Columbia was diagnosed with H5N1. This is the first domestically acquired case of human H5N1 infection in Canada. The teenager initially experienced conjunctivitis, fever, and cough, which rapidly progressed to acute respiratory distress syndrome, requiring intensive care. Genomic sequencing revealed that the virus belonged to the 2.3.4.4b clade, genotype D1.1, consistent with strains found in wild birds in the Fraser Valley area and not directly related to outbreaks at poultry farms in British Columbia. The D1.1 is a different genotype than the one that has infected dairy workers in the U.S. and the child in California. Testing of household contacts of the patient, pets, nearby animals, and environmental samples returned negative results for influenza H5 and despite several efforts, health officials were not able to identify the definitive source of the teenager’s infection.

In a media briefing, Bonnie Henry, British Columbia’s health officer said that the “virus may have evolved after infecting the patient”. The reason for suspecting this is because the teenager’s symptoms began with conjunctivitis and then rapidly progressed to acute respiratory distress syndrome. Serial samples from the patient have been collected to identify any mutations that may have occurred over the course of the infection.

While no further cases were detected, genomic analysis of the viral isolate identified mutations in the virus that are potentially linked to increased adaptation to human hosts, including enhanced cell-receptor binding and deeper lung penetration. Genome sequencing identified the PB2-E627K mutation in the sample, which is linked to faster replication in human cells and greater severity of illness, and likely emerged during the infection. These findings raise concerns about the potential of the virus to cause more severe respiratory illness in humans. However, there is currently no evidence that the H5N1 virus infecting the teenager in Canada has been transmitted to other people.

Concurrently, the U.S. CDC confirmed the first human case of H5N1 avian influenza in a child from Alameda County, California. The child experienced mild respiratory symptoms and is recovering after antiviral treatment. Health officials have found no evidence of human-to-human transmission, as family members tested negative for the virus. Although over 50 cases of human H5N1 infections have been reported from the U.S. in 2024, this patient is the second child in North America to be infected with H5N1. 

The two cases are particularly concerning because their transmission routes differ significantly from the other cases of H5N1 that have been reported from North America in 2024. Previous infections primarily involved people who were in close contact with infected birds, including dairy or poultry farm workers. According to the CDC, human H5N1 infections without a clear link to exposure to affected animals are rare and have predominantly been reported in other countries. These recent cases, therefore, underscore the importance of understanding the virus’s evolving genomic characteristics, which may allow it to bypass traditional transmission barriers. Researchers are particularly vigilant for mutations that could enable the virus to spread more easily among humans, as such changes could pose a significant public health risk.

While these findings underscore the urgent need for understanding and addressing the evolving epidemiology of the H5N1 virus, they also highlight the need for increased surveillance and targeted public health interventions to control the virus’s spread. Continued genomic surveillance of the virus will be critical to tracking its evolution, understanding mutation patterns, and assessing its potential to adapt and spread more effectively among human populations. Such efforts are essential to guide prevention strategies and mitigate the risk of a potential H5N1 pandemic.

(Bani Jolly is a senior scientist and Vinod Scaria is a senior consultant at Karkinos Healthcare)