As Human Cases of H5N1 Rise, Experts Voice Concerns About Mutations

Experts and agency lead continue to voice concerns over H5N1 bird flu as cases rise in animals and humans across the United States and Canada. Cases of severe illness, namely those in Louisiana and British Columbia, have garnered concern over possible mutations in the virus that lead to increased risk of human-to-human transmission. In light of rising cases of norovirus, respiratory syncytial virus, and COVID-19 during the winter season, there is potential for co-infections. These could create conditions that facilitate viral mutations or enhance their resilience in certain environments.¹

Blood test sample with H5N1 influenza | Image Credit: © diy13 - stock.adobe.com

Prevalence of H5N1

As of January 2025, all 50 states have H5N1 outbreaks in poultry, which include both commercial farms and backyard flocks. Cases are also rising in cattle and dairy cows, which have been reported across 16 states, primarily California, Colorado, Michigan, and Texas. H5N1 cases have also been confirmed in pets and other wild animals. There is concern that this may eventually impact pig populations as well.^2-5

“Pigs are on farms with chickens and with cows, and chickens and cows can infect, with their virus, a pig, and then a human virus can go into [a] pig, and then you could get a reassortment of a virus that has some of the dangerous qualities of H5N1 and some of the capability of spreading from human to human of a human virus,” Anthony Fauci, MD, former director of the National Institute of Allergy and Infectious Diseases and professor at Georgetown University's School of Medicine and School of Public Policy, said on a podcast with Scientific American. “So that’s what public health officials are concerned about: that when you have the circulation of this virus in multiple species, including a ‘mixing bowl’ species like a pig, you might get a reassortment and a mutation that could make this something we really have to be concerned about.”⁵

As of January 6, 2025, the CDC has reported 66 confirmed cases in humans in the United States; however, this may be an incorrect count due to lack of public awareness of H5N1 symptoms and testing availability. The majority of these cases can be linked back to exposure to infected animals and the CDC has not disclosed any cases of human transmission in the United States. Although very rare, they have reported cases of probable limited, non-sustained, human-to-human transmission in other countries.^2,6

Mutations and Severe Cases

Although many cases are mild, 2 hospitalizations of severe illness revealed mutations to the virus that may help facilitate an increased likelihood of human-to-human transmission. The first case reported by the CDC took place in Louisiana where an unidentified male patient over the age of 65 was hospitalized in critical condition with respiratory symptoms after exposure to dead birds in a backyard flock. Based on genetic sequencing of the patient’s nasopharyngeal and oropharyngeal samples, they identified unique mutations that were not seen in samples from infected birds.⁷

H5N1 particles illustration | Image Credit: © c_ART_oons - stock.adobe.com

Similar mutations were seen in another hospitalization case of a 13-year-old female patient in British Columbia. According to a paper on her case published in the New England Journal of Medicine, prior to hospitalization she experienced symptoms including conjunctivitis in both eyes, fever, cough, vomiting, and diarrhea. This escalated to severe respiratory distress with hemodynamic instability, which was followed by respiratory failure, pneumonia in the left lower lobe, acute kidney injury, thrombocytopenia, and leukopenia, leading to her eventual hospitalization in the pediatric intensive care unit. Signs of progression to acute respiratory distress prompted tracheal intubation and venovenous extracorporeal membrane oxygenation.⁸

Genomic sequencing of the patient’s tracheal-aspirate specimen showed similar mutations to those seen in the Louisiana case, indicating increased binding to receptors that facilitate viral entry into cells in the human respiratory tract and enable viral replication. These mutations, in both cases, are suspected to have most likely emerged during infection as the virus replicated.^7,8

Increasing Awareness of H5N1

Heightened public awareness of H5N1 bird flu is essential for early detection and effective response. Recognizing symptoms—such as conjunctivitis, fever, respiratory issues, muscle aches, vomiting, and diarrhea—is critical for timely intervention, particularly among individuals with known exposure to infected animals. These efforts can help limit the spread of the virus and reduce the likelihood of severe cases or co-infections with other circulating pathogens.⁹

As the situation surrounding H5N1 evolves, the CDC is tracking cases and closely monitoring the virus's spread and potential mutations. Public health authorities, along with health care professionals, must work together to maintain a high level of awareness, ensuring that the public is informed about the symptoms of H5N1 and the importance of early testing and intervention. The continued collaboration between healthcare providers, public health agencies, and the community will be crucial in minimizing the impact of H5N1 and preventing further mutations that could pose greater risks to public health.

REFERENCES

1. Rust S. ‘Worrisome’ mutations found in H5N1 bird flu virus isolated from Canadian teenager. Los Angeles Times. December 31, 2024. Accessed January 6, 2025. https://www.latimes.com/environment/story/2024-12-31/worrisome-mutations-found-in-h5n1-bird-flu-virus-isolated-from-canadian-teenager

2. H5 bird flu: current situation. CDC. January 3, 2025. Accessed January 6, 2025. https://www.cdc.gov/bird-flu/situation-summary/index.html

3. HPAI confirmed cases in livestock. USDA. December 20, 2024. Accessed January 6, 2025. https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/hpai-confirmed-cases-livestock

4. Avian influenza in pets and backyard flocks. American Veterinary Medical Association. Accessed January 6, 2025. https://www.avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza/avian-influenza-companion-animals

5. Why Anthony Fauci is concerned about bird flu and public division. Scientific American. December 4, 2024. Accessed January 6, 2025. https://www.scientificamerican.com/podcast/episode/anthony-fauci-warns-of-bird-flu-dangers-and-how-public-division-could-make/

6. Past examples of probable limited, non-sustained, person-to-person spread of avian influenza A viruses. CDC. February 27, 2023. Accessed January 6, 2025. https://www.cdc.gov/bird-flu/php/avian-flu-summary/h5n1-human-infections.html

7. Genetic sequences of highly pathogenic avian influenza A(H5N1) viruses identified in a person in Louisiana. CDC. December 26, 2024. Accessed January 6, 2025. https://www.cdc.gov/bird-flu/spotlights/h5n1-response-12232024.html

8. Jassem A, Roberts A, Tyson J, et al. Critical illness in an adolescent with influenza A(H5N1) virus infection. N Engl J Med. December 31, 2024. doi: 10.1056/NEJMc2415890

9. Bird flu (avian influenza). Cleveland Clinic. December 5, 2024. Accessed January 6, 2025. https://my.clevelandclinic.org/health/diseases/22401-bird-flu#management-and-treatment