Outbreak preparedness: Have we learned from COVID-19?

In 2020, the world stopped to tackle COVID-19; a global threat that had no regard for country borders, socioeconomic status, race or gender. There were some amazing achievements with COVID-19 lab diagnostics being rolled out in February 2020, point of care tests receiving emergency use authorization (EUA) in March, new COVID-19 monoclonal antibodies in November and new vaccines developed within the year. Together these helped us regain control. 

However, our response to this virus was reactive. We hadn’t heeded the warnings that we were unprepared for a global pandemic and hadn’t made changes following the SARS (2002-2003) or influenza A (H1N1) (2009-2010) outbreaks. Vulnerabilities showed. We saw global leaders wrangling to obtain medical tools for their own countries at the expense of access for all. Low- and middle-income countries lost out especially those in Africa, despite calls from experts that “no one is safe, until everyone is safe”. Since then, there have been many calls to do things differently, but what have we learned? And have we put these lessons into practice?

With this year's WHO public health emergency of international concern (PHEIC) and Africa CDC public health emergency of continental security (PHECS) announced for mpox, the outbreak of Marburg in Rwanda and concerns about influenza A (H5N1), these questions are again at the fore.

At Impact Global Health, we interrogate these questions objectively using our rich funding and product pipeline databases to hone in on research and development (R&D). We have faithfully tracked global health R&D investments in emerging infectious diseases since the 2014 Ebola outbreak, adding diseases we track to mirror those listed as priorities by the WHO R&D Blueprint team.

COVID-19 saw unprecedented levels of R&D funding to support the development of new medical countermeasures. Much of this came from the public sector with the US government an instrumental player. This is a pattern we see across the pandemic preparedness sector (as highlighted in the 100 Days Mission Scorecard we co-created with the International Pandemic Preparedness Secretariat - IPPS). We also see high industry investment which is not replicated in other diseases with outbreak potential. When national biosecurity is at risk, high-income countries dig deep to support R&D and when there is a commercial market, industry responds. However, not all outbreaks attract the same attention or investment.

^{Figure 1: COVID-19 and mpox R&D funding disbursements for diagnostics, therapeutics and vaccines}

In 2023, we began tracking R&D funding for mpox after the 2022 PHEIC. Here, we can see the reactive nature of global funding persists with a peak coinciding with the outbreak and trough when the threat is deemed to be over (in 2023). This pattern leaves us underprepared for the next outbreak which for mpox came this year. With the current mpox PHEIC, children are a key affected group. However, even though we have approved mpox vaccines, they are not yet approved for children and so further clinical testing during the outbreak has been necessary before this vulnerable group can be protected. This limited our ability to quickly control the outbreak.

The level of mpox R&D investment is significantly smaller than COVID-19. There are several reasons for this.

• We already have approved vaccines for mpox which is different to our starting position for COVID-19.
• Products that were approved for other members of the orthopoxvirus family, like smallpox, were used for mpox.
• Mpox causes different medical problems than COVID-19 and isn’t as easily spread.
• Mpox cases are concentrated in Africa and while there have been cases reported outside of the continent, it is bearing the greatest burden.
• As with COVID-19, US government funding dominates mpox R&D. However, we see less industry investment in contrast with COVID-19 which has a commercial market.

When we look at the development pipeline for these diseases, each has unique successes and challenges.

When COVID-19 hit we were unprepared. Medical tool development had to start from scratch, although we were able to build upon existing knowledge (e.g. from HIV research) and made some significant strides in vaccine platform technology with the approval of the first mRNA vaccine. With large investment, diagnostics, monoclonal antibodies and vaccines were all developed and approved within the year. These timeframes were dramatically faster than the usual speed of product development especially for vaccine development which can take 10 years. It shows what we can do with focus and funding. We now have a full complement of approved COVID-19 products with many options available. While we are seeing appropriate reductions in funding and contraction of the COVID-19, it remains buoyant compared to that of other diseases with outbreak potential such as Lassa fever.

In contrast, the mpox pipeline in 2024 is different. We already had three approved vaccines when the PHEIC was announced, although they were not approved for use in all populations, for example children and pregnant and lactating women. Children have represented a high burden group and we have seen trials activated to test approved vaccines in this group during the outbreak. One vaccine (Bavarian Nordic MVA-BN vaccine) has now received WHO prequalification for use in adolescents, but could we have done more during or after the 2022 PHEIC to have been better prepared this time? Children are known to be commonly affected by endemic mpox; could the approved vaccines have been tested in this vulnerable group sooner? At the start of the PHEIC, there were repurposed smallpox medicines like tecovirimat being trialled for mpox. However, an NIH study recently concluded that while this medicine is safe, it doesn’t resolve mpox symptoms. More innovative, newer therapeutics for mpox remain at early stages of development. We have seen progress with mpox diagnostics which was a large gap at the start of the PHEIC. One hundred days after the PHEIC was announced, two lab based molecular tests, and one point of care diagnostic had received WHO emergency use listing which has helped move away from relying on clinical diagnosis.

While the R&D funding supporting outbreak response remains reactive and greater product development progress needs to be made between outbreaks, there are signs of hope from our response to the mpox outbreak. The leadership and ownership of Africa CDC has been notable with the 2024 mpox outbreak being the first time the organization announced a PHECS to mobilize continental resources. The collaborations between Africa CDC and WHO and other key players such as CEPI, Gavi, FIND and Unitaid have built on the lessons of COVID- 19. This month we also heard that Bavarian Nordic, the owners of the MVA-BN mpox vaccine, entered into an agreement with the Serum Institute of India to expand manufacturing of this approved vaccine. However more work remains to address all the lessons from COVID-19. For example, no mpox vaccines are being manufactured in Africa which leaves the continent still reliant on imports.

If you are keen to learn more about the pandemic R&D ecosystem, check our G-FINDER data that has just been updated this month and our infectious disease R&D tracker. For deeper analysis you can read our recent emerging infectious disease report that looked at the impact the WHO R&D blueprint priority pathogen list had on R&D funding.

Our data also lies at the centre of the 100 Days Mission Scorecard that we first curated last year and have updated this year in partnership with IPPS. The second scorecard will be published on 31^st January 2025 with key insights and actionable recommendations as part of the IPPS annual implementation report.

Through our engagement with the pandemic preparedness community, we hear calls for tracking global R&D for ongoing outbreaks in real time. However, it’s not clear who should do this work. We have experience in this space and stand ready to share our data with all who need it to help inform their funding, product development, policy or advocacy work. If you don’t see what you need on our website, get in touch as we may already be working on the data you need behind the scenes.