Could there be another pandemic, and are we ready?

Covid may not be the last pandemic we experience in our lifetime. Experts suggest we are not well prepared – even for diseases arising from known pathogens such as flu or coronaviruses. So what about an unknown? Katrina Megget reports

The global Covid death toll now sits at more than 7m people[1]. But despite this damning statistic, the Independent Panel for Pandemic Preparedness and Response (IPPPR) recently concluded: ‘The world remains unprepared to stop an outbreak from becoming a pandemic’[2].

According to the IPPPR, countries are not investing the resources required for pandemic preparedness and response, with $10-15bn more in international finance needed to fill the gaps. ‘In an interconnected world where 100,000 commercial flights land every day, we are only as safe as the weakest link in the chain,’ the report says. ‘The world is not ready for a new pandemic threat.’

The risk of another pandemic is high. The H5N1 strain of bird flu has recently made a surprise appearance in cattle farms in the US, for example, infecting four people in contact with sick cows, while a man in Mexico died from another bird flu strain (H5N2) never before recorded in humans.

In August 2024, meanwhile, the World Health Organization (WHO) launched a global strategic preparedness and response plan to stop outbreaks of human-to-human transmission of mpox. The WHO had already declared a public health emergency for the virus, which has killed more than 500 people. And then there’s the virus known as Oropouche or sloth fever that’s currently spreading around the Americas, transmitted by biting insects. Since the start of 2024 there have been more than 8000 cases and two deaths. There are no approved vaccines or treatments.

Evidence suggests the probability of another pandemic occurring within our lifetime is about 17%. But some predictions suggest this could reach 44% within the next couple of decades because of climate change, urbanisation, deforestation, intensive farming and international travel[3]. The WHO recently listed more than 30 priority pathogens that could start a pandemic[4].

But knowing when the next pandemic will strike is difficult. ‘The next pandemic could be beginning right now,’ says Amesh Adalja, senior scholar, Johns Hopkins Center for Health Security, US. The highest threat comes from respiratory viruses such as flu and coronaviruses, he says, but we shouldn’t discount other pathogens. ‘When it comes to pandemic pathogens, there is more preparedness for influenza because it is the highest risk pandemic pathogen and we have vaccines and antivirals as well as diagnostics,’ Adalja says. ‘We are generally well prepared for coronaviruses, as well, after Covid-19. But outside of these two viral families, there is very little by way of medical countermeasures.’

Pandemic preparedness encompasses political leadership and finance through to surveillance and a global response system. However, it’s medical countermeasures (MCMs) – diagnostics, vaccines and treatments – that are crucial when a pandemic threat arises. Speaking about the initial lack of specific MCMs in the armoury for Covid-19, Baroness Hallett – the Chair of the UK Covid-19 Inquiry on the resilience and preparedness of the UK – referred to the belief the next pandemic would be influenza, where antiviral drugs were already available, and vaccines could be tinkered with to match the flu variant circulating[5].

Learning from this failure led to the 100 Days Mission, developed in 2021 by scientific, governmental and industry experts to improve the response to a future pandemic. The goal is that safe, effective and affordable diagnostics, vaccines and therapeutics are available to be produced at scale within 100 days of a pandemic threat being identified. Central to achieving this goal is the need to strengthen R&D. In line with this, the WHO’s associated R&D Blueprint aims to rapidly activate R&D activity during epidemics.

The development of vaccines – in just nine months – changed the course of the Covid pandemic (see C&I, 2024, 88, 12, 30). This effort was partly spurred by the US Government’s Operation Warp Speed public-private partnership, which enticed vaccine manufacturers to accelerate development, manufacture and distribution, while the Coalition for Epidemic Preparedness Innovations invested in a variety of vaccine technologies. However, the speed the Covid vaccine was developed was only possible because of 15 previous years of coronavirus research, Adalja emphasises.

Today, the world is well prepared for Covid. And for flu; there are two types of authorised pandemic influenza vaccines – those based on the 2009 H1N1 swine flu pandemic (of which the US FDA has licensed four) and those targeting avian flu H5N1 (of which three have been FDA licensed). In the US, several hundreds of thousands of doses of bird flu vaccines are currently stockpiled and scale up agreements with pharma firms could see tens of millions of doses available within a four- or five-month period. Whether that is sufficient to provide vaccine coverage to at-risk populations, however, is unknown.

For mpox, vaccines are available, but access is concentrated in Western countries rather than in the African countries where they are most needed. The risk is that hoarding vaccines does little to prevent a pandemic from occurring and also points to the need for increased regional manufacturing capacity.

However, several priority pathogens listed by the WHO do not have an approved vaccine, including Lassa fever, Nipah virus and Zika. The severe haemorrhagic Ebola virus, which has an average fatality rate of 50%, would have fallen into this category if not for pharma firm Merck, known as MSD outside the US and Canada, collaborating in late 2014 to develop a live recombinant viral vaccine. This has since been approved for use in the US and EU for the prevention of disease caused by Zaire ebolavirus, one of the six identified Ebola virus species, and is registered for use in 11 African countries. It took five years to develop the vaccine Ervebo, with clinical trials taking place in an outbreak setting during the West African 2014-2016 epidemic. Studies showed a 100% efficacy with no confirmed cases in subjects vaccinated in immediate vaccination clusters, compared with those in delayed vaccination clusters, a Merck spokesperson says. According to a recent study in The Lancet, real-world effectiveness is closer to 84%[6].

‘Ervebo is the only vaccine for which efficacy has been established, given the challenges of conducting trials in outbreak settings,’ according to Merck. ‘The rapid development and deployment of a Zaire ebolavirus vaccine is a public health triumph and a testament to the power of global partnership and collaboration.’

The vaccine has been used in six outbreaks, with more than 300,000 doses administered. As of March 2023, more than half a million doses have been stockpiled for future outbreaks in low and middle-income countries. A separate stockpile is maintained in the US. Unfortunately, Ervebo is only effective against one of the Ebola viruses – albeit the most common.

Research into next-generation pandemic vaccines is ongoing. The success with mRNA-based vaccines for Covid has flowed through to other diseases. US biotech Moderna, for instance, has an mRNA vaccine for bird flu in Phase 2 trials and one for mpox in Phase 1/2 trials. There is also much research into ‘universal’ flu vaccines that have cross-protection against all flu strains and variants, as well as research into novel adjuvants – ingredients used in vaccines that boost the immune response. These novel adjuvants could increase the number of vaccine doses manufactured by reducing the amount of antigen required in each dose.

Treatment options

Vaccines bring a pandemic under control by preventing spread and severity of disease. However, they aren’t a cure for those who get sick. ‘In a pandemic, you have to act quickly and move fast and if a new virus arises it takes time to develop vaccines so [in the meantime] you need drugs that treat the disease,’ says Naomi Maria, Assistant Professor of medicine at the Donald and Barbara Zucker School of Medicine, Hofstra University, US. The FDA has approved six antivirals to treat flu while the antiviral remdesivir has been approved for the treatment of Covid.

But there are gaps. Of eight virus families with a high potential to cause a future pandemic (excluding influenza), five have no FDA approved drugs and four of those have no drugs in US-Government funded clinical trials[7]. The report authors partly point to market forces for why more R&D isn’t being carried out and call for more ‘push’ and ‘pull’ incentives.

But for Maria, the solution is simpler. ‘I think we have more in our arsenal than we realise,’ she says, pointing to repurposing already approved drugs and using AI to accelerate the process. ‘There are many drugs out there that could be useful for a future virus.’

In research published in 2023, Maria and colleagues created an algorithmic tool called the PHENotype SIMulator or PHENSIM for short. The tool simulated tissue-specific infection of host cells with Covid and then performed computer experiments to identify existing drugs that could be potential treatment candidates. This included the corticosteroid methylprednisolone and diabetes drug metformin. The team confirmed the validity of the tool by comparing its results with published in vitro studies of the drugs[8].

‘Besides metformin, there are so many other drugs out there [we could explore] to see what happens to the immune system when we use them,’ Maria says. Screening for suitable treatments that already exist and are deemed safe could take just days versus the traditional 10-12 years for the development of new drugs, she adds.

But for this to work, a better understanding of viruses, their effect on the immune system and sharing of data is required, says Maria’s co-author, Ashley Duits, medical immunologist, Red Cross Blood Bank Foundation, Curaçao. ‘What we need for AI is to have sufficient data made available by other research groups. With the Covid pandemic that was one of the positive things, and that idea is still being promoted.’

The preparedness picture – which importantly also includes diagnostics (see Box) – is grim. That’s the case even for a pandemic arising from a known pathogen. But what about Disease X, a pandemic pathogen we aren’t aware of? Covid, for instance, fell into this category. Adalja says this is an area that could be prioritised. ‘Very little funding for infectious disease preparedness is designated to Disease X,’ he says, although this has increased a little in recent years.

One way to approach the unknown is having potential pandemic virus families on the radar; previous coronavirus research is a case in point during the Covid pandemic. ‘Work in adjacent members of pandemic viral families would be really impactful towards pandemic preparedness’, Adalja says. In this case, medical countermeasures against one member of a viral family could easily be altered to target another family member.

Equally, the time for action is during non-pandemic times. That requires not just investment, but also leadership. ‘The Covid-19 pandemic illustrated what a modern pandemic can look like in terms of its rapidity of spread, death toll and economic and societal disruption,’ Adalja says. ‘This should galvanise people to recognise that it is critically important to be adept at pandemic preparedness and to be proactive.’

Diagnostics shortage

Pandemic preparedness and response will be insufficient if diseases can’t be detected or diagnosed in the first place. ‘Diagnostics are vital in a pandemic,’ says Devy Emperador, Senior Scientist, pandemic threats, at the Swiss non-profit Foundation for Innovative New Diagnostics (FIND) which advocates for equitable access to reliable diagnostics. ‘Without them we would not know what’s circulating, in which populations and how best to treat and prevent disease.’

That said, worldwide stockpiles for diagnostics, other than Covid, are limited. ‘Several diseases including Lassa fever, Crimean-Congo haemorrhagic fever and Nipah virus are still missing sufficient diagnostics,’ Emperador says. At the end of 2021, there were no WHO-approved diagnostic tests for six of the WHO’s then 10 priority diseases. Even for Covid, it was five months after the first reported case before the first commercial lateral flow tests were approved to enter the market.

Part of the problem is that diagnostics are often considered the ‘poor relation’ when it comes to pandemic medical countermeasures. ‘This is due to the limited interest and investment in the space,’ Emperador says. She believes this can be addressed by investing in initiatives geared towards diagnostics R&D and production. To achieve the 100 Days Misson for diagnostics, FIND estimates an initial investment of $80-100m seed funding is needed to catalyse the full investment required.