Tackling an avian influenza virus strain with pandemic potential should be straightforward — if lessons from the COVID-19 pandemic are heeded.

In January 2020, when the World Health Organization declared the outbreak of SARS-CoV-2 a public health emergency of international concern, there was no vaccine, no antiviral therapeutic, and a general lack of clarity of the natural viral reservoir, how it spread, who was most at risk of severe disease, and the case-fatality rate.

Fast-forwarding to today, the world may again be on the cusp of a fresh pandemic, as the avian influenza virus H5N1 strain (clade 2.3.4.4b) that has been decimating US poultry flocks has now jumped to dairy cattle and, of greatest concern, to humans.

But the collective understanding of the threat is very different this time around, and that knowledge, coupled with effective communication of accessible public health interventions, can compensate for a near-term shortage of vaccines and targeted therapeutics.

Avian influenza virus has been known to circulate in birds since the late 1800s. The virus belongs to the influenza A virus (IAV) group, with highly pathogenic forms capable of causing mass death in bird populations. It was not until 1997 that the first human case of H5N1 avian influenza was reported in Hong Kong, in an outbreak that led to 18 human infections, 6 deaths, and the culling of millions of domestic birds to stem further virus spread1.

The high death rate in humans was a global wake-up call. National influenza pandemic plans were created, vaccines were developed, approved and stockpiled, surveillance was ramped up, and poultry were vaccinated. But a vaccine against avian influenza for humans was never rolled out to the public.

With 144 possible avian influenza virus subtypes, and no effective universal influenza vaccine design thus far, a vaccine against avian influenza for use in humans might seem unattainable. But according to the US Centers for Disease Control, only six avian hemagglutinin subtypes have infected humans and resulted in respiratory illness, and of those, H5N1 and H7N9 viruses have caused the most human cases, which narrows the list of potential vaccine candidates. Despite sporadic human cases of infection, human-to-human spread of avian influenza has thus far been infrequent and not sustained. However, influenza virus is highly mutable and could give rise to a highly human-transmissible and virulent avian influenza virus variant, which would require a pandemic response.

Whether the H5N1 virus currently infecting both poultry and dairy cattle in the United States poses a greater risk of triggering a human pandemic than previous strains capable of zoonotic infection is unknown. The virus has been circulating in the United States since at least January 2022, when it was first detected in wild birds and subsequently in poultry facilities. H5N1 infections in humans and other mammals have been reported worldwide, associated with exposure to birds, which highlights the potential for broader zoonotic transmission of this virus. But the detection of H5N1 in cows, a species not previously thought to be susceptible to IAV, in the United States in March 2024, and the subsequent reports of — at the time of this writing — three cases of cow-to-human transmission in dairy farm employees have raised concerns about the threat potential of this IAV if it adapts to become both endemic and highly pathogenic in mammals.

The US Department of Agriculture has taken steps to aid affected dairy producers navigate the outbreak, including the release of funds to producers who supply personal protective equipment to their employees, for the development of biosecurity plans, and for veterinarian and testing costs. Other countries, such as Mexico and France, have been vaccinating their poultry flocks against H5N1. Millions of domestic fowl worldwide have been culled in the current outbreak.

Vaccination of poultry may help quell localized outbreaks, but the rapid evolution of IAV and its continual reintroduction by wild birds makes this approach a short-term fix in the absence of a universal vaccine. And although culling of poultry has been economically viable, thanks to government subsidies and the rapid growth of birds, it is an infeasible solution for cattle. Instead, infrastructural changes need to be adopted to detect and limit spread of avian influenza virus, particularly in the event that the virus becomes more highly transmissible or virulent.

The lessons from the COVID-19 pandemic are abundant. (1) Surveillance is essential. However, the financial considerations of dairy producers complicate the picture, as they are not incentivized to report a sick animal. Eliminating that barrier is critical to reducing further animal-to-animal spread and reducing the potential for animal-to-human transmission. (2) Protecting agricultural and food industry workers is essential. Just as these employee groups suffered disproportionately severe outcomes from COVID-19 due to a lack of sufficient personal protective equipment, testing, job retention and compensation for quarantining, and affordable medical care, so too must they be at the forefront of addressing the avian influenza outbreak, as populations at high risk of exposure and vulnerable to mistreatment. (3) Inexpensive, noninvasive, rapid tests are essential, both for animals and humans, to facilitate the immediate enactment of precautionary measures. (4) Masks are a critical resource that must be depoliticized. In the absence of a widely available vaccine, masking will mitigate spread of a pandemic influenza virus strain. (5) Communication is essential. Data sharing with local, national and international stakeholders will facilitate an effective response. Engaging, rather than alienating, the public on the development of the outbreak, on both the knowns and unknowns, and of ongoing efforts to mitigate virus spread, is necessary to restore confidence in the public agencies tasked with responding to potential pandemics.

Although the evolution of circulating H5N1 may be unpredictable, the response should not be.