Is There Another Pandemic Coming? Experts Weigh In

Another pandemic is not just possible but, statistically speaking, probable within most people’s lifetimes. An analysis of global epidemic data spanning four centuries found that an event on the scale of the 1918 influenza pandemic has a recurrence time of roughly 400 years at current rates, but that the yearly probability of such a catastrophe could triple in the coming decades due to accelerating environmental change and more frequent animal-to-human disease spillover. The question infectious disease researchers wrestle with is less “if” than “what, when, and how bad,” and the answers depend on a tangle of biology, ecology, economics, and politics that resists simple prediction.

What Four Centuries of Data Actually Show

Researchers compiled a global dataset of epidemics from 1600 to the present and found that the yearly number of epidemics has varied ninefold over that period, with clear upward trends. The probability of extreme pandemics follows a pattern where very large events are rarer but not as rare as you might hope. A 1918-scale catastrophe had a yearly probability ranging from about 0.27% to 1.9% depending on the era examined, and its average recurrence time today sits around 400 years. That might sound reassuringly distant, but the math works differently than most people assume: a roughly 2% annual probability means there is a meaningful chance of experiencing such an event within any given century.

More troubling is the trajectory. Using estimates of how quickly new diseases are jumping from animals to humans, the same analysis projected that the yearly probability of an extreme pandemic could increase up to threefold in the coming decades. That would compress the expected wait time considerably. The researchers emphasized that previous analyses had underestimated the likelihood of catastrophic outbreaks because they relied on short observation windows and treated epidemic risk as static rather than changing over time.

1PubMed Central. Intensity and frequency of extreme novel epidemics

Avian Influenza Is the Threat Experts Watch Most Closely

If you ask virologists which known pathogen keeps them up at night, many will point to highly pathogenic avian influenza A(H5N1), specifically the clade 2.3.4.4b lineage that has been tearing through bird and mammal populations worldwide. The virus has infected a staggering range of species, from poultry and wild birds to sea lions, elephant seals, polar bears, and dairy cattle. The cattle infections are especially alarming because the virus has shown an unprecedented ability to colonize mammary gland tissue, leading to viral shedding through milk and a growing series of infections among dairy farm workers in the United States.

2PubMed Central. Highly Pathogenic Avian Influenza A(H5N1) Virus: How Far Are We from a New Pandemic?

The critical question is whether H5N1 can acquire the ability to spread efficiently between people. So far, no sustained human-to-human transmission has been documented, and that single missing piece is the barrier between a worrying zoonotic outbreak and a full-blown pandemic. But researchers are actively tracking the molecular changes that could close that gap. A set of mutations in a key viral protein called PB2 have been identified in virus samples taken from cattle and other mammals between 2021 and 2024. In laboratory experiments, these mutations dramatically boosted the virus’s ability to replicate in mammalian cells and caused more severe lung damage in mice.

3PubMed Central. Identification and characterization of PB2 mutations associated with mammalian adaptation of highly pathogenic H5N1 avian influenza viruses

The fact that these mammalian-adaptation mutations are already circulating in animal populations, rather than being hypothetical laboratory constructs, is what gives the threat its urgency. Each new mammalian host the virus enters is another chance for it to accumulate the changes needed for human-to-human spread. Research into other amino acid mutations that could expand the virus’s host range is ongoing, with scientists emphasizing that deeper characterization of these changes is essential for understanding which evolutionary paths the virus might take.

4PubMed. Viral protein mutations enabling mammalian adaptation in Avian Influenza A viruses: Strategies for zoonotic risk mitigation and future perspectives

Why New Diseases Keep Jumping from Animals to Humans

The accelerating pace of new infectious diseases is not random bad luck. It is driven by specific, measurable changes in how humans interact with the natural world. Several interconnected factors are pushing more pathogens from animal reservoirs into human populations.

Deforestation and land-use change are among the most powerful drivers. When forests are cleared for agriculture or development, the animals that live in them do not simply vanish. Many species, including rodents and certain birds that carry viruses, adapt to the edges of fragmented habitat and come into closer contact with people and livestock. The relationship is not straightforward, though. Research suggests that even forest recovery can increase risk: as tree cover returns to previously cleared areas, reservoir species rebound and move back in, potentially bringing pathogens with them into zones where human settlements already exist.

5PubMed Central. Outbreaks of Vector-Borne and Zoonotic Diseases Are Associated With Changes in Forest Cover and Oil Palm Expansion at Global Scale
6BioScience. The land-use land-cover change–emerging infectious disease nexus reconsidered

Wildlife trade amplifies the problem enormously. Billions of organisms move through legal and illegal markets every year, creating conditions that are almost tailor-made for viral spillover. Wildlife markets, where live wild-caught and captive-exotic animals are kept in close proximity to each other and to people, provide ideal environments for pathogens to jump species. Major outbreaks including HIV/AIDS, SARS, MERS, Ebola, COVID-19, and avian influenza have all been linked to wildlife trade and spillover at the human-animal interface.

7PubMed Central. Potential zoonotic spillover at the human-animal interface: A mini-review
8Advances in Animal and Life Sciences. Wildlife Trade and Zoonotic Spillover

Southeast Asia faces particularly elevated risks due to the convergence of rapid environmental change, biodiversity loss, and extensive wildlife trade networks. Qualitative research into market practices in the region has found that wildlife markets are locations where the conditions for zoonotic spillover are actively amplified by the way animals are transported, stored, and sold.

9SSM – Qualitative Research in Health. Selling spillover: a qualitative study of wildlife trade and market practices in Southeast Asia

Industrial livestock production adds another layer of risk. Keeping large numbers of farm animals in crowded, stressful conditions increases the chances of pathogen emergence, transmission, and amplification, including zoonotic diseases with pandemic potential.

10Animal Research and One Health. Links between industrial livestock production, disease including zoonoses and antimicrobial resistance

The Enormous Pool of Viruses We Have Not Met Yet

H5N1 is a known threat, but pandemic preparedness experts are equally concerned about pathogens that have not yet been identified. An estimated 1.7 million undiscovered viruses exist in the natural environment across diverse host species, and many of these are predicted to be capable of infecting humans. The concept of “Disease X,” a placeholder term used by the World Health Organization to represent a future pandemic caused by an as-yet-unknown pathogen, captures this uncertainty.

11PubMed. The natural virome and pandemic potential: Disease X

Bats alone harbor an extraordinary diversity of viruses with known spillover potential, including coronaviruses, filoviruses (the family that includes Ebola), and paramyxoviruses. In Southeast Asia, researchers estimated that a median of roughly 66,000 people are infected with SARS-related coronaviruses from bat populations every year, most of whom likely experience mild or no symptoms and never come to medical attention. These silent infections represent a constant churn of opportunities for a virus to adapt to human hosts and gain the ability to spread between people.

12PubMed Central. A strategy to assess spillover risk of bat SARS-related coronaviruses in Southeast Asia
13Current Opinion in Virology. Viruses in bats and potential spillover to animals and humans

The sheer scale of uncharacterized viral diversity means that cataloguing what exists in animal reservoirs and understanding the conditions that lead to spillover is one of the central challenges in pandemic prevention. The more host-virus association data scientists collect, the better they can estimate which viral families pose the greatest threat and focus surveillance resources accordingly.

14PubMed. Global estimates of mammalian viral diversity accounting for host sharing

Climate Change Is Reshaping Where Diseases Can Spread

Rising temperatures are redrawing the geographic boundaries of infectious disease in ways that will expose hundreds of millions of people to threats they have never faced. Mosquitoes that carry dengue, Zika, chikungunya, and yellow fever are expanding their ranges toward the poles as temperatures warm. Modeling work projects that under severe climate change scenarios, nearly a billion people could face new exposure to these mosquito-borne viruses within the next century. Europe is expected to see substantial increases in transmission risk in the near term, while parts of Southeast Asia and West Africa may see shifts toward more seasonal rather than year-round risk from certain mosquito species.

15PubMed Central. Global expansion and redistribution of Aedes-borne virus transmission risk with climate change

Permafrost thaw adds a more exotic but scientifically real concern. As the Arctic and subarctic warm, long-frozen ground is releasing organic material that has been locked away for thousands of years, raising the question of whether dormant pathogens could reemerge and cause outbreaks. The actual risk from ancient permafrost viruses remains debated and is likely low compared to the more immediate threats from living animal reservoirs, but it has attracted serious scientific attention.

16PubMed Central. Cooling perspectives on the risk of pathogenic viruses from thawing permafrost

Detection Tools That Did Not Exist Before COVID-19

One genuinely encouraging development is the expansion of wastewater surveillance from a niche research tool into a mainstream public health system. During the COVID-19 pandemic, cities around the world began routinely testing sewage for viral genetic material, and the approach has proven to be a powerful early warning system. Wastewater monitoring can detect rising pathogen levels in a community days or weeks before clinical cases show up in hospitals, giving health authorities a critical head start.

17PubMed Central. Wastewater Surveillance for Early Warning of Infectious Disease Outbreaks: A Systematic Review of Evidence and Implications for One Health Surveillance

The technology has advanced rapidly. Beyond simply detecting a single virus, newer sequencing methods applied to wastewater can identify circulating strains, track mutations, and even spot entirely different pathogens that were not the original target of testing. Untargeted RNA sequencing of sewage samples has identified several pathogens beyond SARS-CoV-2, raising the possibility that wastewater networks could serve as a broad-spectrum sentinel system for emerging threats.

18PubMed Central. Feasibility of neighborhood and building scale wastewater-based genomic epidemiology for pathogen surveillance

This matters because speed of detection is one of the few variables in pandemic response where improvement translates almost directly into lives saved. The earlier you know a new pathogen is spreading, the sooner you can deploy containment measures. And that speed matters more than ever in a world where air travel networks can carry a virus across continents within hours. Research has confirmed that air network connectivity is a major contributor to how fast viral transmission spreads globally.

19Transport Policy. The effects of air transport mobility and global connectivity on viral transmission: Lessons learned from Covid-19 and its variants

The Prototype Pathogen Strategy for Faster Vaccines

The COVID-19 vaccines were developed in record time, but “record time” still meant nearly a year before the first doses reached arms. For the next pandemic, researchers are trying to compress that timeline further through what is called a prototype pathogen approach. The idea, formalized by the National Institute of Allergy and Infectious Diseases in a 2021 preparedness plan, is to do as much vaccine and therapeutic groundwork as possible before a pandemic starts by selecting representative viruses from each major viral family and developing candidate vaccines against them in advance.

20PubMed Central. Prototype Pathogen Approach for Vaccine and Monoclonal Antibody Development: A Critical Component of the NIAID Plan for Pandemic Preparedness

If, for example, a novel paramyxovirus emerged tomorrow, scientists would not be starting from scratch. They would already have a vaccine platform tested against a related paramyxovirus prototype, along with manufacturing processes and preliminary safety data. The platform could then be adapted to the specific new virus far more quickly than building everything from the ground up. This strategy treats pandemics the way fire departments treat fires: you do not wait for the alarm to start building the truck.

Gain-of-function research, where scientists deliberately enhance a pathogen’s transmissibility or virulence to study it, remains a contentious part of this preparedness landscape. Such work can yield important insights into how viruses evolve to become more dangerous, but it also carries biosecurity and biosafety risks that prompted the Obama administration to pause federal funding for certain experiments involving influenza, SARS, and MERS viruses in 2014. The debate over where the line should be drawn continues in the scientific community.

21PubMed Central. Gain-of-Function Research: Ethical Analysis

The WHO Pandemic Treaty and Who Gets the Vaccines

Scientific preparedness only works if the tools it produces reach the people who need them. One of the starkest lessons of COVID-19 was the grotesque inequality in vaccine access: wealthy countries secured doses months or years before many low-income nations could vaccinate their most vulnerable populations. WHO member states have been negotiating a Pandemic Treaty intended to prevent a repeat of that failure, with equity as a stated foundational principle.

22PubMed Central. Equity in the Pandemic Treaty: Access and Benefit-Sharing as a Policy Device or a Rhetorical Device?

The treaty establishes a system designed to link the sharing of pathogen samples and genetic sequence data with equitable access to the vaccines, diagnostics, and treatments derived from them. It also creates a global supply and allocation mechanism and includes financing provisions to help lower-income countries build manufacturing and distribution capacity. Whether these mechanisms will function in practice during the pressure of an actual crisis remains an open and deeply political question. Intellectual property barriers, national self-interest, and manufacturing bottlenecks all worked against equity during COVID-19, and the treaty’s provisions will need to overcome those same forces.

23PubMed Central. Global Health Governance and the WHO Pandemic Agreement: A Scoping Review of Challenges and Analysis of Reforms

Antimicrobial Resistance as a Parallel Slow-Burn Crisis

While viral pandemics capture public attention, antimicrobial resistance is sometimes described as a “silent pandemic” already underway. Bacteria, fungi, and parasites that no longer respond to the drugs designed to kill them are a growing cause of death worldwide, and the COVID-19 pandemic made the problem worse. Widespread antibiotic use during COVID-19, much of it unnecessary, accelerated resistance patterns that had already been worsening for years.

24PubMed Central. Flare of the silent pandemic in the era of the COVID-19 pandemic: Obstacles and opportunities

Antimicrobial resistance does not look like a traditional pandemic. There is no single outbreak, no dramatic surge in cases. Instead, routine infections and surgeries gradually become more dangerous as the drugs that once treated them lose effectiveness. Industrial livestock production contributes to the problem by using antibiotics at scale, creating reservoirs of resistant organisms that can pass to humans. A future where a novel virus triggers a pandemic while healthcare systems are simultaneously struggling with untreatable bacterial infections is not a hypothetical doomsday scenario; it is a plausible compound crisis that preparedness planning needs to account for.

10Animal Research and One Health. Links between industrial livestock production, disease including zoonoses and antimicrobial resistance

Misinformation and the Human Side of Pandemic Response

Even with perfect surveillance, fast vaccines, and equitable distribution, a pandemic response can fail if people do not trust the institutions running it. COVID-19 demonstrated this vividly. Misinformation spread through social media lowered people’s willingness to get vaccinated, reduced adherence to public health guidelines, and undercut compliance with basic preventive measures. The result was decreased public trust in science that made health messaging less effective at precisely the moment it mattered most.

25PubMed Central. A Comprehensive Analysis of COVID-19 Misinformation, Public Health Impacts, and Communication Strategies: Scoping Review

Research has confirmed that this is not just a perception problem: misinformation measurably erodes trust in health institutions, which in turn undermines the performance of health governance systems. On the other side, studies of compliance during COVID-19 found that higher trust in government was associated with greater adherence to precautionary measures, and that this relationship worked partly through people’s awareness of the problem itself. When people trusted the messenger, they took the threat more seriously and acted accordingly.

26Telematics and Informatics Reports. Examining the impact of misinformation on governance efficacy in the health sector: The mediating role of public trust and the moderating effect of social media regulations
27PubMed Central. When and How Trust in Government Leads to Compliance with COVID-19 Precautionary Measures

For the next pandemic, this means that the information environment is as important as the scientific one. Countries that have invested in clear, honest communication channels and maintained some baseline of institutional credibility will respond more effectively than those where trust has been hollowed out, regardless of how good their vaccines or surveillance systems are.

What Prevention Actually Costs Compared to the Alternative

One of the more striking findings in pandemic preparedness research is how cheap prevention is relative to the cost of doing nothing. A comprehensive analysis of primary prevention strategies, including wildlife trade regulation, livestock biosecurity improvements, and reduced deforestation, found that these measures cost less than one-twentieth the value of lives lost each year to emerging viral diseases that jump from animals to humans. The interventions also carry substantial co-benefits, from biodiversity conservation to reduced carbon emissions.

28PubMed Central. The costs and benefits of primary prevention of zoonotic pandemics

Engineering controls in the built environment represent another underfunded layer of protection. Research during COVID-19 made a strong case that improving ventilation, air filtration, and air disinfection in public buildings, from schools and offices to hospitals and public transit, would significantly reduce indoor transmission of airborne pathogens. These are not exotic technologies. They are upgrades to existing building systems that would pay dividends against seasonal influenza, tuberculosis, and any future airborne pandemic pathogen, not just the one that prompted the research.

29PubMed Central. How can airborne transmission of COVID-19 indoors be minimised?

The political challenge is that prevention spending competes with immediate needs and lacks a visible constituency. Nobody throws a parade for the pandemic that did not happen. But the math is unambiguous: investing a fraction of what a pandemic costs into reducing the likelihood and severity of the next one is among the highest-return public expenditures available to any government.