Decoding Disease X: What is the unknown pathogen threatening the world?

By Rabia Ali

ISTANBUL (AA) - It was in 2018 when Dr. Amesh Adalja, an infectious disease specialist in the US, started thinking about and working on Disease X, realizing that pandemic preparedness was “stultified” and that people were mostly focusing on influenza.

“Disease X has been something that for the last six or seven years people in my field have been really trying to develop a framework around to make the world more resilient to pandemic threats, even if they come from something that we haven’t characterized yet,” Adalja told Anadolu in a video interview.

A senior scholar at the Johns Hopkins Center for Health Security, Adalja’s concerns were not without ground.

The World Health Organization (WHO) has recently ramped up its efforts and discussions about this unknown infectious pathogen that experts warn may trigger the next pandemic.

In January, WHO chief Tedros Adhanom Ghebreyesus expressed hope that countries will reach a pandemic agreement by this May to address this “common enemy,” warning that a global health emergency was now “a matter of when, not if.”

In an email to Anadolu, the WHO said a global agreement to protect against future pandemics is under discussion by its member states, and it stands ready to support the accord once agreed by all.

The WHO said it aims to strengthen cooperation, coordination, governance and investment “needed to prevent a repeat of the devastating health and socioeconomic impact caused by COVID-19, (and) make the world better prepared for (a) future pandemic.”

According to the WHO, Disease X is a “placeholder term often used to refer to a potential unknown pathogen that could cause a future pandemic or health crisis, and to remind the world that we need to prepare for unknown diseases along with known threats.”

In 2017, the WHO published its first list about diseases that had the potential to cause a severe epidemic, for which it says “we don’t have enough or no known medical countermeasures.”

The list, which urges donors, researchers and scientists to focus on specific diseases with epidemic potential, mentioned Disease X in 2018.

According to WHO’s Tedros, COVID-19, which claimed more almost 7 million lives worldwide, was the first Disease X.

- Likely to be a respiratory virus

Adalja also explained that Disease X is a placeholder concept that does not have any real definition or real reference.

However, he said it is most likely to be a respiratory virus caused by a zoonotic pathogen, meaning that it could be spread from animals to humans.

It is most likely that “a pandemic pathogen is going to be a virus because of their ability to mutate,” he said.

“It’s also most likely to be something that spreads through the respiratory route,” said Adalja.

An infection that spreads through the respiratory route can really do so prolifically and it is very difficult for interventions to stop it the way an intervention could stop something that might be spread through blood and body fluids, he explained.

Adalja pointed out that there are many respiratory viruses that circulate in animals, particularly mammals, that could develop the ability to spread efficiently in humans.

However, it might not necessarily be from an animal, he stressed.

“It could be one of the other viruses that infect humans or evolves new characteristics or qualities to be able to spread. Or a human virus could be combined with an animal virus,” he added.

- Origins and emergence

The infectious disease expert pointed out that zoonotic risks are very high when it comes to the Disease X pathogen.

“We think that they would emerge in places that there’s a lot of human-animal interface,” he said.

However, he said there is no way of being sure, pointing to the emergence of the H1N1 virus from Mexico, a country that “was not on anybody’s list of a place where a pandemic pathogen might emerge.”

“It’s not always going to be in hotspots in Africa and Asia where there’s high levels of biodiversity,” he said.

“We shouldn’t be completely blinded to the fact that we could get a pandemic from North America.”

- What to look out for

A likely scenario with any Disease X outbreak would be a surge in cases of pneumonias and upper respiratory infections, according to Adalja.

“When a Disease X emerges, it’s likely to present in some country with a cluster of unexplained pneumonia cases, just like COVID did,” he said.

That makes it important for countries to have the diagnostic capability “to understand what’s causing people to be sick with pneumonia and respiratory illnesses,” he said.

“Part of Disease X is going to be really being much more aggressive with diagnostic testing of things that are making people sick all over the world,” said Adalja.

That is particularly important because there “could be cases of unknown pathogens that are spreading in humans that are not causing much disruption and are going unnoticed because our diagnostic paradigm is not very robust when it comes to infectious disease,” he warned.

For example, prior to COVID, most people did not test to see what was making people come into hospitals with pneumonia, he explained.

- Preemptive possibilities

While Disease X may yet be a placeholder concept, the expert emphasized that there are still steps that can be taken to counter it.

“The principle with Disease X is that you can work in those viral families ahead of time, because Disease X is likely to come from maybe a half dozen or so viral families that have very prolific respiratory viruses,” he explained.

Categorization of viruses and understanding how they make people sick can be done, along with understanding their transmission characteristics and what parts of that virus might be important for an immune response, he continued.

He said vaccines can be developed ahead of time and might need to be tailored to the specific pathogen that ends up emanating as a pandemic pathogen or as an infectious disease emergency.

For example, he pointed out that SARS-CoV-2, the cause of COVID-19, was a Disease X.

“It wasn’t on anybody’s list, it was not known to humans before 2019, and yet we were able to make a vaccine within less than a year,” said Adalja.

“That vaccine was developed because people had been working on other viruses in the coronavirus family, for example … the work done on MERS (Middle East Respiratory Syndrome) allowed people to move very quickly when SARS-CoV-2 was discovered and categorized.”