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Could the Next Pandemic Come from an Unknown Disease? Are We Ready to Face It?

The COVID-19 pandemic continues to impact the world, but scientists remain vigilant, closely monitoring potential pathogens that could trigger another Next Pandemic global health crisis.

Next Pandemic

Next Pandemic Before the COVID-19 pandemic, the World Health Organization (WHO) identified a list of priority infectious diseases deemed significant threats to global public health. These diseases required further research to enhance their surveillance and diagnosis. In 2018, the list introduced the concept of “disease X  ,” representing an unknown pathogen with the potential to spark a pandemic.

This acknowledgment highlighted the limits of our understanding of the microbial world we inhabit. However, recent efforts have shifted towards developing systematic approaches to mitigate future pandemic risks.

Former U.S. Secretary of Defense Donald Rumsfeld once described “known knowns” (things we are certain of), “known unknowns” (things we recognize as uncertainties), and “unknown unknowns” (things we are unaware of entirely). While originally controversial in the context of weapons of mass destruction, this framework offers valuable insights into how we can prepare for future pandemics.

Influenza: A ‘Known Known’

Influenza serves as a prime example of a “known known.” Each year, we experience a mini-pandemic as the virus undergoes minor changes. However, significant mutations occasionally arise, leading to widespread infection among populations with little or no pre-existing immunity. This occurred during the 2009 swine flu pandemic.

Despite being familiar with influenza, many aspects remain uncertain, such as what drives its mutations, how these changes interact with population-level immunity, and how to accurately predict transmission patterns, severity, and yearly impacts.

The H5N1 Avian Influenza: A Growing Concern

Currently, the H5N1 subtype of avian influenza, commonly known as “bird flu,” has spread extensively worldwide. This outbreak has caused the deaths of millions of birds and has crossed species barriers, infecting mammals such as cows in the U.S. and marine mammals in South America.

Human cases have been reported among individuals in close contact with infected animals. Fortunately, no sustained human-to-human transmission has been observed so far. However, the situation underscores the ever-present risk of influenza evolving into a larger threat.

The current H5N1 subtype of avian influenza (“bird flu”) has spread widely around the world. It has led to the deaths of many millions of birds and spread to several mammalian species including cows in the United States and marine mammals in South America.

Human cases have been reported in people who have had close contact with infected animals, but fortunately there’s currently no sustained spread between people.

As we navigate these challenges, the pressing question remains: How can we better prepare for the next “disease X”? Understanding and addressing these risks will be essential to safeguarding global health.

Next Pandemic

(Image credit: DIGICOMPHOTO/SCIENCE PHOTO LIBRARY via Getty Images)

Detecting influenza in animals is a monumental challenge, particularly in large countries like Australia. However, systems are in place to monitor and respond to bird flu in both wildlife and livestock.

Given the nature of influenza, it’s inevitable that future pandemics will arise. Yet, the ones we worry most about may not always be the ones that come to pass. For instance, attention focused on avian influenza intensified in 1997 after an outbreak in birds in Hong Kong caused severe human illness. However, the pandemic that followed in 2009 originated from pigs in central Mexico, proving that the next pandemic could come from unexpected sources.

Coronaviruses: An ‘Unknown Known’

While Donald Rumsfeld didn’t specifically mention “unknown knowns,” coronaviruses certainly fit into this category. Before the COVID pandemic, we already knew more about coronaviruses than most people realized. The world had already experienced significant outbreaks, such as the Severe Acute Respiratory Syndrome (SARS) and the Middle Eastern Respiratory Syndrome (MERS). Both were caused by coronaviruses closely related to SARS-CoV-2, the virus responsible for COVID. Although these earlier outbreaks faded from the public’s focus, coronaviruses were still recognized as potential pandemic threats and were included in the World Health Organization’s 2015 list of diseases with pandemic potential.

Previous research into SARS and MERS proved essential in responding to COVID-19. The work done by the Oxford team on developing a MERS vaccine laid the foundation for the rapid creation of AstraZeneca’s COVID vaccine. Similarly, prior research into the structure of the coronavirus spike protein — which enables the virus to bind to human cells — was crucial for the development of mRNA vaccines, such as those produced by Pfizer and Moderna.

It’s clear that coronaviruses are likely to remain a significant threat in the future. While future coronavirus outbreaks may not match the scale of COVID-19, their impacts can still be devastating. Take MERS, for instance: when it spread to South Korea in 2015, it only resulted in 186 cases over two months, but the cost of controlling the outbreak was estimated at a staggering US$8 billion (A$11.6 billion).

As the world grapples with the ongoing challenges of managing COVID-19, the broader question of preparing for future pandemics looms larger. Understanding and learning from past outbreaks, whether from avian influenza or coronaviruses, will be critical in shaping our response to the next health crisis.

Next Pandemic

An illustration of the coronavirus. (Image credit: Shutterstock)

The 25 Viral Families: Addressing ‘Known Unknowns’

The focus is now shifting toward the known unknowns. There are approximately 120 viruses across 25 families that are known to cause human diseases. These viral families share common characteristics, and our immune systems typically respond to them in similar ways.

One example is the flavivirus family, which includes well-known viruses like yellow fever and dengue fever. Other members of this family include Zika virus, which can lead to birth defects when pregnant women are infected, and West Nile virus, which can cause encephalitis (brain inflammation).

The World Health Organization’s (WHO) blueprint for epidemics emphasizes the need to evaluate threats from various classes of viruses and bacteria. By examining pathogens from each viral category, the goal is to expand our knowledge systematically.

The U.S. National Institute of Allergy and Infectious Diseases (NIAID) has taken this a step further by developing vaccines and therapies targeting prototype pathogens from major viral families. This proactive approach allows for the adaptation of knowledge to create new vaccines and treatments should a pandemic emerge from a closely related virus.

Pathogen X: The ‘Unknown Unknown’

Then, there are the unknown unknowns—pathogens that are completely unknown to us but have the potential to cause severe global epidemics. This concept is encapsulated by the term disease X. To prepare for such unpredictable threats, we need to adopt new surveillance methods that specifically target areas where new pathogens could emerge.

In recent years, there’s been a growing understanding that we must broaden our view of health. Rather than focusing solely on human health, we need to consider the health of animals and the environment as well. This holistic perspective is captured in the concept of One Health, which considers how factors like climate change, intensive agricultural practices, trade in exotic animals, encroachment into wildlife habitats, international travel, and urbanization contribute to the emergence of new diseases.

A Global Approach to Reducing Risk

This approach has critical implications not only for identifying potential sources of new infectious diseases but also for minimizing the risk of “spillover”—the transmission of diseases from animals to humans. To combat this, scientists are recommending targeted testing of animals and individuals working closely with them. Currently, most testing is focused on known viruses. However, emerging technologies offer the possibility of identifying previously unknown viruses in patients exhibiting symptoms that might indicate a new infection.

We live in a vast, interconnected world filled with potential microbiological threats. While influenza and coronaviruses have a history of causing pandemics, a growing list of unknown pathogens could still lead to outbreaks with significant consequences.

To reduce the risk of future pandemics, continued surveillance of new pathogens is essential. Additionally, improving our understanding of key viral families and implementing policies to reduce the risk of animal-to-human transmission will play crucial roles in safeguarding global health.