What is Disease X? Experts say most people will see another pandemic this lifetime

World better-prepared to handle it should another pandemic arrive tomorrow, but there are no fool-proof antidotes to ‘unknown unknowns’

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Most people on the planet will witness another pandemic like COVID-19 in their lifetime, according to leading infectious disease experts, as they warn the world is still ill-equipped to deal with the looming threat of ‘Disease X’ – an unknown pathogen with the potential to spread rapidly around the globe.

The World Health Organization (WHO) coined the term ‘Disease X’ in 2018 to refer to a currently unknown infectious disease capable of causing a serious international epidemic. Global experts say the next pandemic is looming, and Disease X serves as a reminder that the next pandemic could be started by a pathogen currently unknown to science.

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By this definition, COVID-19 – the pandemic that brought global economies to their knees, claimed millions of lives, and exposed global weaknesses in pandemic preparedness – was the first ‘Disease X’ event.

A man wearing a protective face mask walks past an illustration of a virus outside a regional science centre, as the city and surrounding areas face local restrictions in an effort to avoid a local lockdown being forced upon the region, amid the coronavirus disease (COVID-19) outbreak, in Oldham, Britain August 3, 2020. (Reuters)
A man wearing a protective face mask walks past an illustration of a virus outside a regional science centre, as the city and surrounding areas face local restrictions in an effort to avoid a local lockdown being forced upon the region, amid the coronavirus disease (COVID-19) outbreak, in Oldham, Britain August 3, 2020. (Reuters)

Dr. Thomas Rawson, Epidemiology Research Associate at Imperial College London’s Jameel Institute, told Al Arabiya English the severity of ‘Disease X’ is unknown – but could have the ability to be even more fatal than COVID-19 – the death toll of which stands at more than seven million, according to the latest statistics by Worldometer.

‘Pandemics becoming more likely’

“Pandemics are becoming more and more likely,” said Dr. Rawson. “As human populations grow, and with it our interactions with animal disease sources, so too grows the risk of a novel pathogen emerging. It is likely that many of us will be personally affected by another global pandemic in our lifetimes.”

“It’s important, therefore, for the world to be ready – not just with treatments, vaccinations, messaging, stockpiled resources, individuals with the necessary skill sets, and healthy populations to begin with (e.g. those with no obesity, underlying disease, and so on), but also with the ability to scale up responses and act quickly.”

While the specifics remain unknown, experts say ‘Disease X’ will likely share some key traits that enabled previous pandemics to spread globally.

“It is likely to spread through respiration, likely to be a virus, likely to be something that could spill over from an animal species into a human,” said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security.

In a Q&A published by the John Hopkins Bloomberg School of Public Health, Adalja said – like COVID-19 – the next pandemic is likely to be spread through respiration, “because that’s more efficient for a pathogen.”

“People talking, laughing, coughing, sneezing – all of that is very hard for public health to intervene in, as we saw with COVID-19. It’s likely to be a virus, not bacteria or fungus. It could spill over from an animal species, or it could be a human pathogen that develops new characteristics or changes its genetics in such a way that makes it more conducive to causing a pandemic.”

In terms of location, Adalja notes that while areas with high human-animal interaction may seem obvious hotspots, “the last pandemic before COVID-19 – 2009 H1N1 pandemic – originated in Mexico, which wasn’t considered a hotspot.”

Adalja said there are known knowns, known unknowns, and unknown unknowns.

“With ‘Disease X,’ we’re preparing for an unknown unknown,” he said. “ ‘Disease X’ is a placeholder concept that refers to a pandemic pathogen that has not yet been characterized. Its purpose is to encourage proactive thinking about pathogens that could cause a pandemic and push people’s thinking forward, so that they’re not wedded to lists of prior pandemic pathogens, like influenza.”

“There are many pathogens that have the potential to cause a pandemic that might not yet be in humans. They often come from viral families with certain characteristics that lend themselves to becoming pandemic pathogens. The concept of ‘Disease X’ allows people to proactively work in those viral families, to start thinking about how they are transmitted, how they impact the human body, and what types of immune responses are important. All of that can start ahead of time, which increases our resilience because people aren’t waiting for something to first be characterized as a pandemic pathogen and start working on it,” Adalja said.

Test tube with Coronavirus name label is seen in this illustration taken on January 29, 2020. (Reuters)
Test tube with Coronavirus name label is seen in this illustration taken on January 29, 2020. (Reuters)

Preparing for the next pandemic

Speaking at a World Economic Forum (WEF) panel in Saudi Arabia this April, WHO Director-General Tedros Ghebreyesus acknowledged that the world remains vulnerable to another pandemic on the scale of COVID-19.

“We are unprepared, and we’re still vulnerable to the same problem,” he said at the time. However, he expressed optimism about a potential international agreement currently being negotiated, which would establish “a structure for pandemic prevention, preparedness, and response.”

An agreement that will help establish a structure for pandemic prevention has been in the works since 2021. “[It] will help us prepare better and prevent the same thing like COVID from happening,” Ghebreyesus said as he delivered his report to the 76th World Health Assembly in May last year.

“The key is to have a binding pandemic agreement that member-states will respect. So, if anything happens, the best is to prevent it. And that’s why we are building capacity.”

He added: “In the face of overlapping and converging crises, pandemics are far from the only threat we face,” he added, underscoring the need for effective global mechanisms that address and respond to emergencies of all kinds.

“When the next pandemic comes knocking – and it will – we must be ready to answer decisively, collectively, and equitably,” he advised.

The need for ‘data pipelines’

Rawson emphasizes the importance of “efficient data pipelines” to quickly gather and share information during the next pandemic.

He said that COVID-19 was arguably the first global pandemic of the information age. Infodemic management and communication stood out in this pandemic compared with previous pandemics, but the last pandemic of comparable severity to COVID-19 was the so-called ‘Spanish Flu’ influenza in 1918.

While the specifics remain unknown, experts say ‘Disease X’ will likely share some key traits that enabled previous pandemics to spread globally. (File photo)
While the specifics remain unknown, experts say ‘Disease X’ will likely share some key traits that enabled previous pandemics to spread globally. (File photo)

When it comes to COVID-19, Rawson said in 2020, when the disease was declared a global pandemic, “lots of rich and useful data was able to be logged, shared, and used in real-time” to help respond to the outbreak.

“Information on case numbers, hospital outcomes, genetic mutations, and disease severity (such as how lethality varied by age) was rapidly gathered,” he said.

“This meant that we could quickly answer some of the most important epidemiological questions in the early months of 2020 – ‘How quickly is it spreading?’ ‘How lethal is it?’ ‘How much of it is already circulating?’. These questions are critical to informing just how much healthcare capacity you need to start preparing.”

“Given we need a lot of data to be collected quickly to respond to a pandemic well, it’s important to have very efficient ‘data pipelines’ – systems in place to ensure that information is shared as quickly and accurately as possible.”

In 2020, said Rawson, these surveillance systems and data pipelines needed to be built from scratch, and many countries struggled in the first few months of the pandemic.

“When the next pandemic occurs, we want to be in a position to respond faster, reusing much of the technology developed for COVID-19.”

“Good data allows us to optimally allocate limited resources in the early stages of a pandemic.”

Indeed, said Rawson, countries that had experienced outbreaks of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) had a head start during COVID-19. These countries already had infrastructure in place for tracing respiratory illness outbreaks.

Vaccine development

As the World Health Organization continues to work toward finalizing a landmark global agreement on handling future pandemics on prevention, preparedness, and response, Rawson said COVID-19 has taught the world some valuable lessons – and results.

“A huge success in 2020 was the sheer speed of vaccine development,” he said. “The science of vaccine development has made huge strides in the last decade, and now allows us to develop vaccines against new diseases far more rapidly than earlier.”

But a remaining challenge is making the huge quantities of vaccines needed in a pandemic fast enough, he said.

“In 2020, rich countries had faster access to vaccines than poorer ones, and next time we would like to do better in giving more equitable access to vaccines to the entire world’s population.”

“This is an ongoing challenge not just logistically (some vaccines need to be stored at very low temperatures, which makes them tricky to ship), but politically as well, as countries will tend to prioritize securing sufficient vaccinations for their own populations first.”

The biggest challenge according to Rawson is that different diseases need to be tackled in very different ways, making pandemic preparedness a difficult task.

“As such, pandemic preparedness isn’t about being ready to respond to a specific disease, it’s about being able to react quickly to address a wide range of possible diseases.”

He said most diseases are usually characterized by two measures – their transmissibility, and severity.

Diseases that are very severe, such as Ebola, require high-quality critical-care beds and highly targeted case-tracing and quarantining responses, explained Rawson.

Meanwhile, less severe but more transmissible diseases require large stockpiles of PPE (personal protective equipment), and to prepare general hospitals for large numbers of in-patients.

And the biggest problem?

“These stockpiled resources don’t last forever. Vaccines, PPE, and medicines all have best-before dates,” he said. “And having an empty, fully staffed, hospital on standby 24x7 is unfeasible.”

“When national governments have so many immediate priorities that require attention and financing, it can be easy for pandemic preparedness items to slip down the agenda. Nobody wants to spend lots of money on something that doesn’t get used.”

“We also need to sustain the global networks between scientific and health professionals that were formed across disciplines during the [COVID-19] pandemic, despite the growing geopolitical divisions in today’s world. These ensure existing expertise is captured, shared, utilized, and carried over to the next generation of scientists, policymakers, and governments.”

Doses of the Pfizer-BioNTech vaccine against the coronavirus disease (COVID-19) are pictured at a booster clinic. (File photo: Reuters)
Doses of the Pfizer-BioNTech vaccine against the coronavirus disease (COVID-19) are pictured at a booster clinic. (File photo: Reuters)

Learning from COVID-19

Rawson said the huge swathes of COVID-19 data – and vital takeaways from that pandemic – will take decades to fully analyze and learn from.

“Research funded by philanthropic foundations like Community Jameel is crucial to unlocking all the lessons from the last pandemic (and other disease outbreaks) to improve our response to future threats.”

“Within Imperial, we’ve been undertaking retrospective analyses to answer questions like how to best apply and use limited vaccine stockpiles; how to quantify the real-world impact of different intervention methods; how different communities and sub-populations were affected differently during the COVID-19 pandemic, and how we can better protect these communities in future. To name just a few.”

Rawson said what is crucial – and can help a quicker global response in future pandemics – is to ensure that the world has a consistent in-flux of appropriately trained professionals to help respond to mass outbreaks of disease.

“One of the things we prioritize is partner-led research with other international organizations and the development of easy-to-use software tools to help train a brand-new generation of epidemiologists,” he said.

Gaps in pandemic preparedness

As there are gaps in pandemic preparedness, Rawson said “Every scientist you ask will give you a different answer as to what the biggest gap and priority are.”

“Personally, I’d say the biggest area for ongoing international development is surveillance. Due to the exponential ways that pandemics grow (one case becomes two, becomes four, becomes eight, becomes 16 …), you can quickly be overwhelmed with new cases if you don’t catch a new pathogen early enough. And catching it early means having programs in place so that when people go to their doctor with general symptoms, a certain subset of these individuals have samples taken and tested in a lab, just to check that it’s not something completely new.”

The problem, said Rawson, is that this is both expensive to run, and not always politically advantageous.

“During the COVID-19 pandemic, countries that declared cases early could find themselves cut off from the international community through travel and trade restrictions. Making sure that all countries can adequately track the spread of new (and existing) diseases, and not be punished for declaring novel pathogens,” he said.

Pandemics will always stretch health systems to the limit, he pointed out.

“We’ve learned a lot about non-pharmaceutical interventions (NPIs) through COVID-19, but gaps in understanding remain.” These include how to best use interventions such as the social distancing rule, and also mass vaccination.

“(This is) an interdisciplinary question, spanning epidemiology, health economics, and behavioral science (“how will people react?”),” said Dr. Rawson. “Many countries faced challenges during the COVID-19 pandemic in trying to fine-tune these interventions to optimize disease prevention while trying to limit impacting on the day-to-day functioning of the economy and civil liberties.”

“We are now better prepared than we were in early 2020, but the negative impacts of quarantines and lockdowns mean that governments will be cautious to apply the same measures again in a hurry.”

Workers and volunteers are tested as they conduct their duties in a compound where the residents are tested for the Covid-19 coronavirus during the second stage of a pandemic lockdown in Jing' an district in Shanghai on April 1, 2022. (AFP)
Workers and volunteers are tested as they conduct their duties in a compound where the residents are tested for the Covid-19 coronavirus during the second stage of a pandemic lockdown in Jing' an district in Shanghai on April 1, 2022. (AFP)

Preparedness – not prevention

These complex knowledge gaps point to the need for pandemic preparedness – and not pandemic prevention said Rawson.

“A pandemic will pose health burdens greater than day-to-day operational capacity, meaning responding will always prove a challenge. If pandemic X arrives tomorrow (and if we noticed it early enough) we’d have something of a head start compared to COVID-19 – thanks to our existing vaccine-development infrastructure, the data tools and computer software we developed, and the experienced frontline healthcare staff.”

“However, this assumes that pandemic X behaves like COVID-19, and it assumes that global economies have recovered sufficiently to take the next hit. In many ways, we won’t know for sure how well we’ve learned lessons until Pandemic X arrives. It would be prudent then to ensure that when it does, we’re agreed on how we’ll assess our collective preparedness.”

In the last six years – planning for the concept of ‘Disease X’ – has led to some notable achievements, said Adalja.

“BioNTech and Moderna had a SARS-CoV-2 vaccine candidate ready within hours to days because of work that was done in response to the MERS epidemic in the Arabian Peninsula, like understanding how to stabilize the spike protein in order to engender the appropriate type of antibodies.”

“Even though we didn’t know SARS-CoV-2 would be a pandemic pathogen, people started to think that the coronavirus family was an important viral family to work with because of its ability to cause severe respiratory disease. All of that sped the vaccine up considerably, saving lives.”

However, with the possibility that “ ‘Disease X’ could be arising right now … and it could arise anywhere,” more work needs to be done, cautioned Adalja.

“So, the question is, are we more prepared now than we were for COVID? Yes, probably. But are we fully prepared? No. Have we solved hospital capacity problems? No. Do we have domestic manufacturers of masks? No, most of them have stopped manufacturing after COVID-19 [began to subside]. Do we have a population that wants to embrace new technologies like vaccines and antivirals? No.”

“You can see what happened with the mpox outbreak – how many mistakes were made and how difficult it was to get testing or antivirals. All of that played a major role in how difficult it was for clinicians to actually handle people during the mpox epidemic.”

According to Adalja, the major upside is that vaccine technologies, such as mRNA and adenovirus vaccine platforms, have the ability to really change the response time.

“They can speed up vaccine development to less than a year. Today, organizations such as CEPI [Coalition for Epidemic Preparedness Innovations] are talking about ‘100 Days’ to a vaccine,” said Adalja.

“(Also), the population is able to do home testing, which can be a major counter-offensive in terms of understanding who’s getting infected, letting people know their infection status, and then allowing them to take protective actions.”

But, said Rawson, as the world continues to deal with the fallout from COVID-19 and ‘Disease X’, it serves as a reminder of the need for ongoing vigilance, preparedness, and the ability to quickly adapt and respond to emerging threats.

Read more:

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