What could the next pandemic be?

Coronaviruses

Five years ago coronaviruses would have appeared on few experts’ lists of pandemic threats. In the 35 years since the virus family was first discovered, it had been generally considered a low level pathogen that caused only mild symptoms. That is, until severe acute respiratory syndrome (SARS) in 2002. We then saw Middle East respiratory syndrome (MERS) emerge in 2015, but there was still no anticipation of a pandemic situation like that of 2020, mostly because SARS and MERS were eventually controlled—although the exact reasons SARS petered out are still unknown. SARS, MERS, and covid-19 still appear on WHO’s list of pathogens to watch.

Coronaviruses are common in bats, which make up 20% of all mammal species, and can easily spill over to other mammals such as cats, civets, deer, dogs, and—as the Danish know4—mink. Climate change and further encroachment of humans into animal habitats mean these coronaviruses are coming closer to human populations. And the pandemic has meant that SARS-CoV-2 is now everywhere and humans are seeding new transmission back into other species.

Although coronaviruses generally mutate at a low rate, they do focus—as we all now know—on changes in the spike protein, which could create new variant threats. Immunocompromised patients and those with low or non-existent immunity or in under-resourced settings are most at risk.5

Zika

Zika virus caused panic in 2015-16 when an outbreak in Brazil led to an epidemic across South America and beyond. The virus, transmitted by mosquitoes, had long been known but was thought to cause few symptoms beyond a rash and fever—until that outbreak, when studies found associations between the infection and microcephaly and other neurological disorders in babies. By 2016, WHO declared it a Public Health Emergency of International Concern. Although the epidemic was contained, largely through quarantine and mosquito control, a total of 86 countries and territories have reported evidence of mosquito transmitted Zika infection.6 No vaccine is yet available and our understanding of the way microcephaly develops is still at a relatively early stage. Zika remains on WHO’s list of priority pathogens.

Haemorrhagic fevers

Haemorrhagic fevers are particularly feared because of their symptoms, such as bleeding from the eyes and ears. Ebola continues to be the most notorious, with outbreaks as recently as 2022 in Africa. The 2014 west African epidemic—which spread to several countries and regions, threatening to become a pandemic—is still in public consciousness. It did lead, however, to the development of the first Ebola vaccines, which are now regularly deployed in outbreaks. These vaccines are only effective against one of the two types of Ebola, with a vaccine against the other yet to be proven in large scale clinical trials.

Viral haemorrhagic fevers, transmitted by close contact, also encompass more common diseases: a group known as paramyxoviridae which include measles and mumps. One of these warrants its own mention on the WHO pathogen list: Nipah virus. Small outbreaks have occurred almost annually in Bangladesh and India—the most recent in Bangladesh in January and February 2023 caused eight deaths.7 Though infection can be mild, some patients develop encephalitis. Nipah has a death rate of 40-70% and if it were to develop the ability to spread as fast as measles—which generates 12-18 more infections per case—it would be catastrophic. There are no licensed treatments available.

Five haemorrhagic fevers appear on WHO’s list. Besides Ebola and Nipah are Marburg virus (similar to Ebola), Lassa fever (in some areas of Liberia and Sierra Leone around 10-16% of people admitted to hospitals annually are for Lassa), Rift Valley fever, and Crimean-Congo haemorrhagic fever. These see occasional outbreaks in Africa and Asia in places where the chance of transmission between animals such as bats and rats to humans is a risk.

Influenza

Influenza is not on WHO’s list—ostensibly because, like HIV/AIDS, it already has “established control initiatives.” Many experts, however, still name flu as a major worry. It has a short incubation time of around 1.4 days, allowing it to spread quickly, and is already a major cause of death in humans: in the UK, seasonal flu claims around 10 000 lives annually and, lest we forget, humanity has already experienced several major flu pandemics in the past 100 or so years (1918, 1957, 1968, and 2009). Moreover, the annual flu vaccine is generally only 40-60% effective against the year’s new strains and there remains debate about how effective existing antivirals for influenza are.8

There is also the possibility of a new type of influenza spilling over from the animal kingdom, particularly birds and pigs. There was a swine flu epidemic in 2009, and every year sees a threat from new strains of avian influenza. Transmission from birds to humans is not common but when it does happen it is treated seriously, particularly if it then manages to transmit from a human to another human. In February 2023, alarm was raised when a Cambodian girl and her father died from one of the newest bird flu strains, though thankfully subsequent genetic analysis showed that they were infected with two different strains, so hadn’t transmitted human-to-human. But the situation remains: on 27 March, China reported a new case of avian influenza A (H3N8),9 but no other cases were found among close contacts of the infected person. WHO concluded that, “Based on available information, it appears that this virus does not have the ability to spread easily from person to person, and therefore the risk of it spreading among humans at the national, regional, and international levels is considered to be low.”10

“Disease X”

The last item on WHO’s priority pathogen list is, by definition, a new disease that experts were not expecting, which our bodies have never seen before, and which emerges quickly out of nowhere and demonstrates high transmissibility and severity of disease.

John Mascola, director of the vaccine research centre at the US National Institute of Allergy and Infectious Diseases, told the Financial Times11 that covid has taught us “that we should not underestimate the ability of a virus to emerge and change and adapt” from within a single virus family. Jonathan Quick, adjunct professor of global health at the US Duke Global Health Institute, says that RNA viruses should be treated as “the inner circle of pandemic threats” because they “don’t have very good ‘autocorrects’ in their genetics” and are therefore more likely to mutate than DNA based viruses. Viruses that encode their genome in RNA include coronaviruses, influenza, and HIV.

Beyond viruses, there is also the possibility of other microbes such as fungi or bacteria to cause a major disease outbreak. (A slow moving threat is, of course, already underway in the form of antimicrobial resistance.12)

Nicole Lurie, executive director of preparedness and response at the Coalition for Epidemic Preparedness Innovations (CEPI), tells The BMJ that the world has entered a “new era of infectious disease” because of climate change, the destruction of animal habitats, human encroachment into previously isolated areas, and increasing interactions between people and animals, which is fuelling spillover events and accelerating the emergence of disease X. CEPI chief executive Richard Hatchett has also warned of regional epidemic threats such as malaria, dengue fever, and chikungunya that “are not necessarily diseases that have global pandemic potential but that can be highly disruptive and impose extreme costs on affected societies.”

“We know some diseases have higher pandemic potential, but there is no room for complacency—there is no guarantee that the next pandemic will be caused by a respiratory virus,” says Josie Golding, head of epidemics and epidemiology at Wellcome. “Preparedness should be built into national response frameworks and based on experiences and expertise from low and middle income countries who often bear the majority of the disease burden.”