The World Health Organization maintains a formal list of pathogens most likely to cause the next pandemic, and the list includes a placeholder called “Disease X,” representing a threat that doesn’t yet exist in humans. That concept isn’t hypothetical hand-wringing. COVID-19 was essentially Disease X when it emerged in late 2019, caused by a coronavirus no one had previously identified in people. The next pandemic could come from a known threat like avian influenza or from something entirely unexpected.
WHO’s Priority Pathogen List
WHO’s Blueprint for Research and Development in Emergency Contexts identifies the diseases with the greatest epidemic and pandemic potential. The current priority list includes COVID-19, Crimean-Congo hemorrhagic fever, Ebola and Marburg virus diseases, Lassa fever, MERS and SARS coronaviruses, Nipah and related viruses, Rift Valley fever, Zika, and Disease X. These were selected because they pose significant public health risk and lack adequate treatments or vaccines.
Disease X sits on this list as a deliberate warning. It represents the near-certainty that a pathogen currently circulating in animals, or one that mutates in an unexpected way, will eventually jump to humans and spread efficiently. The leading prediction is that Pathogen X will be an RNA virus (the same category as influenza, coronaviruses, and Ebola) originating in animals, emerging from an environment where deforestation, farming practices, and human-wildlife contact create the right conditions for sustained transmission.
Avian Influenza: The Threat Getting the Most Attention
H5N1 bird flu is the pathogen many experts consider the most plausible candidate for a near-term pandemic. The virus has been circulating in poultry and wild birds for decades, but recent years have seen it spread to mammals including dairy cattle in the United States, an unusual and concerning jump. As of mid-2025, the U.S. has reported 71 human cases of H5 bird flu and 2 deaths since February 2024. Between January and early August 2025 alone, 26 human infections with H5N1 were recorded.
Most of these cases were detected through monitoring of people exposed to infected animals rather than through routine flu surveillance, which means they involved direct animal contact rather than person-to-person spread. That distinction is critical. H5N1 becomes a pandemic threat only if it acquires the ability to transmit easily between people. So far, it hasn’t. But influenza viruses mutate rapidly, and each human infection is an opportunity for the virus to adapt. The combination of widespread animal infections and sporadic human cases makes this a situation global health agencies watch daily.
Active Outbreaks Right Now
Mpox, caused by a newer and more transmissible strain called clade Ib, remains an active global concern. WHO declared it a Public Health Emergency of International Concern twice, most recently lifting that designation in September 2025. But the virus hasn’t gone away. Community transmission of clade Ib persists in at least 11 African countries including the Democratic Republic of the Congo, Kenya, Uganda, and South Africa.
More significantly, the strain is now spreading locally in countries far from the original outbreak zone. Italy, Malaysia, the Netherlands, Portugal, Spain, and the United States are all experiencing community transmission, meaning infections not linked to international travel. In the U.S., public health investigations point to ongoing community spread among men who have sex with men and their social networks in southern California. WHO has extended its standing recommendations on mpox surveillance and vaccine access through August 2026.
Drug-Resistant Bacteria as a Slow Pandemic
Not every pandemic looks like a fast-moving respiratory virus. WHO also tracks antibiotic-resistant bacteria that are steadily becoming untreatable, a crisis sometimes called the “silent pandemic.” In 2024, WHO updated its bacterial priority pathogens list, categorizing drug-resistant organisms into critical, high, and medium priority groups. The most alarming are bacteria resistant to last-resort antibiotics, along with drug-resistant tuberculosis, antibiotic-resistant salmonella, and resistant staph infections. These don’t spread in dramatic waves, but they kill steadily and in growing numbers as treatment options shrink.
What Makes a Spillover Happen
The majority of new infectious diseases in humans originate in animals, a process called zoonotic spillover. Whether a virus makes that jump depends on several converging factors: how common the infection is in animal populations, how densely those animals live near humans, and how genetically similar the animal host is to people. A bat virus, for instance, may need to pass through an intermediate animal (like a pig or a civet) before it can infect human cells efficiently.
Environmental disruption accelerates this process. When forests are cleared for farming, wildlife is pushed into closer contact with livestock and people. Intensive animal farming concentrates thousands of animals in conditions where viruses spread and mutate quickly. Climate change shifts the ranges of mosquitoes and other disease-carrying insects into new territories. None of these drivers are slowing down, which is why the probability of another spillover event leading to a pandemic remains high.
How the World Is Preparing
Global preparedness has shifted substantially since COVID-19. WHO opened a Pandemic and Epidemic Intelligence Hub in Berlin that uses artificial intelligence to scan more than 35,000 data feeds for early signals of outbreaks. The platform, called Epidemic Intelligence from Open Sources, is already used by 43 countries. The Hub also hosts an International Pathogen Surveillance Network focused on genomic sequencing, which allows scientists to identify new variants or mutations within days of their emergence rather than weeks.
The coalition behind the “100 Days Mission” has set an ambitious target: from the moment a new pathogen with pandemic potential is identified, diagnostics, therapeutics, and vaccines should be ready for initial authorization and large-scale manufacturing within 100 days. COVID-19 vaccines took roughly 326 days from viral sequencing to emergency authorization, so hitting 100 days would require major advances in platform technologies, pre-positioned manufacturing, and regulatory speed.
Funding is flowing, though unevenly. The Pandemic Fund, housed at the World Bank, has awarded $885 million in grants across 75 countries to strengthen disease surveillance, laboratory testing capacity, and health emergency workforces in low- and middle-income nations. These are the places where outbreaks are most likely to start and least likely to be caught early.
The New Pandemic Agreement
In May 2025, the World Health Assembly adopted the WHO Pandemic Agreement, the first international treaty specifically designed to govern pandemic preparedness and response. The agreement covers disease surveillance, health system strengthening, research coordination, local manufacturing capacity for vaccines and treatments, and sustainable financing. A central feature is the Pathogen Access and Benefit-Sharing System, which aims to ensure that when a country shares a dangerous pathogen’s genetic information with the world, it also receives fair access to the vaccines and treatments developed from that data. This was a major sticking point during COVID-19, when wealthy nations secured vaccine supplies months before lower-income countries.
The agreement will officially take effect 30 days after 60 countries ratify it through their own domestic processes. Negotiations on the details of the benefit-sharing system are still underway. Notably, the treaty explicitly states that WHO cannot impose lockdowns or vaccine mandates on any country. Implementation depends entirely on each nation integrating the agreement’s goals into its own plans and policies. A Global Supply Chain and Logistics Network, coordinated by WHO, will be established to distribute pandemic-related health products more equitably than the scramble that characterized the early COVID-19 response.
Whether this framework holds under the pressure of an actual emergency remains untested. The infrastructure is more robust than it was in 2019, the surveillance is faster, and the legal commitments are broader. The open question is whether political will and funding hold steady during the years between pandemics, when the urgency feels abstract.