What Will the Next Disease X Be?

The term Disease X is used by the WHO to describe an unknown pathogen that could cause a serious epidemic or pandemic. In this article, Adelaida Sarukhan gives more details.

If the COVID-19 pandemic brought anything good, it was to raise collective awareness of the persistent threat posed by emerging pathogens (i.e. pathogens that appear for the first time in the human population or that were already circulating but behave differently). We have learned that the question is not if there will be another pandemic. The question is when, where and, most importantly, by who.

What is Disease X?

The term Disease X was first used by the WHO in 2018 when it was added to its list of nine priority pathogens - a series of little-known viruses, all of them with an animal reservoir, for which at the time we did not have adequate diagnostics, treatments and/or vaccines. It was called Disease X to emphasise the possibility that the next major epidemic or pandemic could be caused by a previously unknown pathogen.

And so it was. Just two years later, the world was faced with what could be considered the first example of Disease X: COVID-19, caused by a virus (SARS-CoV-2) that we had never seen before but closely related to another that had already entered the human population in 2003 (SARS), and whose reservoir was most likely also the bat.

Since then, Disease X has been the subject of many headlines; even the latest World Economic Forum in Davos dedicated a session to it.

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Candidates and requisites for the next Disease X

When we talk about Disease X, we think primarily - but not exclusively - of a virus. Why is that? For one thing, viruses, especially those that use RNA as their genetic material, have a very high mutation rate, which increases their ability to adapt to new hosts and environments.

Zoonotic viruses

Currently, we know of around 1,400 human pathogens (including viruses, bacteria and fungi), which is a tiny fraction of all potential pathogens that exist in nature, many of them in animal reservoirs (hence the term 'zoonotic'). There are an estimated 320,000 viruses circulating in wild mammals (which have the highest potential to jump to humans). Small rodents and bats alone harbour an enormous diversity of viruses, including coronaviruses, without displaying any apparent disease.

For a zoonotic virus "X" to cause an epidemic in the human population, it has to overcome two hurdles: the first is to jump into our species. This means acquiring the ability to attach itself to a human cell, infect it and cause disease. The second is to achieve human to human transmission. The efficiency of this transmission will largely determine whether the result is a local outbreak, a regional epidemic or a full-blown pandemic.

A well-known but worrying zoonotic virus is avian influenza. With some regularity, it takes the first step - jumping from birds to humans or other mammals

The ideal candidates for causing pandemics are those transmitted through the air, such as SARS-CoV-2. In this category, a well-known but worrying zoonotic virus is avian influenza. With some regularity, it takes the first step - jumping from birds to humans or other mammals. What is new (and alarming) about the H5N1 clade currently affecting domestic and wild birds in virtually all regions of the world is that sustained transmission has been documented in some mammals (farmed ferrets and most likely wild sea lions). Human-to-human transmission has not been reported, but the risk is real.

Latent viruses

With global warming, there is a (remote) possibility that the next disease X will come not from an animal reservoir, but from the past. Specifically, from thawing permafrost, which harbours viruses up to a million years old (older than the human species). Some viruses recovered from Siberian soils have been able to infect unicellular organisms. The risk that any of these could pose a threat to us is low, but it does exist. 

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The Most Feared Pathogens: 9 Diseases that Could Cause a Major epidemic:

Avian Influenza: Should We Be Concerned?

Synthetic viruses

The possibility of creating a synthetic virus with pandemic potential cannot be ruled out either, especially with the help of artificial intelligence. It is therefore important to strengthen global surveillance mechanisms and binding treaties such as the Biological Weapons Convention.

Disease X on the updated list of priority pathogens

Since last year, the WHO has been working with more than 200 experts to update its list of priority pathogens, which is expected to be ready by mid-2024. Thirty viral families and one bacterial group have been assessed for their pandemic potential. Unlike the 2016 list, which focused on specific pathogens, this new list will prioritise entire families of viruses (or bacteria), each with a known prototype pathogen.

The idea is that this document will guide the type of research and tools (diagnostic tests, treatments, vaccines) that should be developed for a prototype pathogen, but that can be rapidly adapted to other members of the same family.

The CEPI global alliance has set as target 100 days to develop, test and produce a new vaccine against pathogen X (COVID-19 took 326 days)

Naturally, disease X will remain on the list of priority candidates. This is important because it allows us to define the type of research and response needed to respond to an unknown pathogen. The CEPI global alliance has set as target 100 days to develop, test and produce a new vaccine against pathogen X (COVID-19 took 326 days). The other goal is to achieve its equitable distribution to avoid what happened with the COVID-19 vaccines.

Preventing and mitigating disease X

We can't stop viruses from mutating, recombining or jumping between species. What we can do is reduce the likelihood of this happening and mitigate the consequences when it does. How do we do this?

Reducing the likelihood starts with banning the trade and sale of wild animals, regulating intensive animal farming, and curbing deforestation and land-use changes (including in the Arctic).

Mitigating the consequences requires not only supporting R&D on priority pathogens, but also strengthening public health, with good genomic and epidemiological surveillance systems to detect outbreaks quickly, and prepared and resilient health systems.

You can also read Después de 29 millones de muertos, el mundo parece no haber aprendido nada, an article by Gonzalo Fanjul, Policy Director at ISGlobal, published in El País - Planeta Futuro.

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