CEPI CEO Dr Richard Hatchett offers his personal reflections on the events of the past year, and asks how well prepared the world now is to deal with future infectious disease threats.
2022 has been another difficult year. The destabilizing impact of the pandemic continues to reverberate, even as the numbers of cases and deaths directly attributable to COVID-19 have declined. The economies of many nations are still wobbling; the war in Ukraine rumbles on; food insecurity is rampant. We have made little tangible progress on climate change. Reflect too much on our current predicament and it is easy to be glum.
So where do we stand now, as this complicated year draws to a close, in the struggle against COVID-19 and other epidemic disease threats? Given all the other crises demanding our attention, how much do we still need to worry about COVID? Can we finally move on? Has the world learned the right lessons from the experience of the last three years? Are we better prepared to deal with future infectious disease threats?
These are perfectly reasonable questions. I am travelling a lot again now, which signifies how far we’ve come, and in most of the countries I visit, the cumulative effects of familiarity and fatigue, widespread access to vaccine for those who want it, and the fact that many if not most people have been infected have resulted in the near complete relaxation of individual and public health precautionary measures. This relaxation has occurred at different rates in different countries, but the phenomenon is universal. In the UK, hospitalizations for influenza recently surpassed hospitalizations for COVID for the first time since the pandemic began. 
That the threat of COVID is perceived by an ever-increasing number of people to have subsided to a level that society can tolerate is a good thing, no doubt. But what we don’t want to do – at least not at the level of politics and policy – and all those other crises notwithstanding – is take our eye off the ball. And frankly it seems hardly the moment to do so from an epidemiologic or public health perspective either, given the so-called “tripledemic” now occurring in countries experiencing high rates of respiratory syncytial virus (RSV), influenza, and COVID-19 simultaneously. Remaining vigilant about a virus that has continually surprised us, even as we “learn to live with it”, is only prudent. COVID has changed dramatically in the short time we’ve been acquainted with it, and it would be foolhardy not to continue to monitor it.
But the world is moving on. On December 7, after weeks of protests, the Chinese government finally began dialing back the Zero-COVID policy that has guided its response to the pandemic since January 2020. China will need to proceed cautiously. Modelers at Hong Kong University warn that relaxing public health measures too quickly, in the absence of other mitigations, could trigger an intense epidemic resulting in up to a million deaths. Even a mitigated epidemic in China will mean vastly more transmission of disease, and every new infection presents the virus opportunities to mutate. 
Another sign that we are slowly returning to business as usual was the recent endorsement by the Gavi Board of a proposal to begin winding down COVAX and transitioning COVID vaccine procurement and delivery to normal Gavi Alliance mechanisms. This will not happen overnight, of course, nor should it – the transition won’t be complete until 2024, and the plan acknowledges that timelines could change if the epidemic intensifies. But recognizing that COVID is here to stay, and that global demand for vaccine is tapering, we need to begin shifting from campaign mode to focusing on integrating COVID immunization into primary care. That process will gather momentum over the course of 2023.
In time, COVAX will take its place in the history books. Its record isn’t unmixed, as anyone who has been paying attention will know. It was assembled on the fly, in a desperate effort to prevent the grossest forms of vaccine inequity – the same kinds of inequity that have always marred the introduction of new medical products and technology, even when severe scarcity and intense global demand haven’t been part of the equation. COVAX has been criticized often and loudly, but its accomplishments must be acknowledged as well. And these are considerable:
–COVAX raised almost $14 billion, supported the development of 14 vaccine candidates, and facilitated access, through procurements and donations, to 11 authorized products.
–COVAX has delivered more than 1.85 billion doses to 146 countries, of which 1.66 billion were delivered to the 92 low- and middle-income countries supported by the COVAX Advanced Market Commitment.
–Primary series vaccine coverage across the populations of the AMC92 countries now stands at 53% overall (compared with global coverage of 63%), with coverage of older adult populations at 66% and coverage of health care workers at 81%.
–Perhaps most impressively, the 57 countries receiving Gavi support for routine immunization increased the number of routine and campaign (largely COVID-19) vaccine doses administered in 2021 by 3.5-fold compared with 2020 (2.85 billion v 851 million).
As one of the people who conceived and then worked hard to bring COVAX to life, I am proud of the impact it has had. But as someone who is also deeply committed to the causes of justice and fairness, I am at the same time mindful of what the world might have achieved but did not.
We can now define that gap, and how many lives were lost in consequence, with some precision, as the MRC Centre for Global Infectious Disease Analysis (GIDA) at Imperial College has recently published an assessment of the global impact of COVID vaccination.  Overall, the authors of this assessment estimated that in the year after the first vaccines were authorized, the global immunization campaign had prevented just under 20 million excess deaths worldwide, including 7.4 million in COVAX AMC countries. These are astounding numbers. But the authors also estimated that while globally immunization had prevented 63% of potential total deaths (19.8 million of an estimated 31.4 million excess deaths in the absence of vaccine), in COVAX AMC countries only 41% of potential total deaths were averted (7.4 million of 17.9 million). Had the COVAX AMC countries had equal access to vaccine, hundreds of thousands or even millions of additional lives could have been saved.
To prevent such tragedies from recurring, we have to understand their root causes. At CEPI, we’ve reflected deeply on our experiences with COVAX and our observations of the global response. A key takeaway from the last three years is that the system and capabilities to respond that we had in 2020 were not configured to produce equity as a natural output of the system’s operation. The initial scarcity of vaccine was a huge problem; but so were the lack of financing mechanisms to enable large-scale, globally distributed production and the lack of healthcare capacity in many countries to deliver vaccines to high-risk populations. The majority of global manufacturing and almost all vaccine development capacity is located in the US, EU, India and China, and vaccine manufacturers located in these regions encountered irresistible pressure to serve these populations first. All of these factors stood in the way of vaccine equity. We would have needed to solve for all of them simultaneously to prevent the inequities that emerged.
The system was perfectly designed to achieve the results it achieved. If we don’t like the system’s output, we will need to reengineer it. And we will need to do so systematically.
Understanding equity as a systems problem is helpful for an organization like CEPI. Some of the factors contributing to inequity CEPI can tackle directly; some we can influence; and some we can only talk about. We can work to minimize scarcity by increasing the speed of vaccine development and production; and we can work with our technical and financial partners to expand vaccine manufacturing capacity in underserved regions, mitigating the problem of vaccine nationalism. While delivering vaccines is not part of CEPI’s remit, we can advocate for the establishment of adult vaccination programs to extend the benefits of routine vaccines to all segments of the population while building capacity to deliver countermeasures against future threats. We can participate in mechanisms like the Pandemic Fund to strengthen new financial mechanisms and instruments and ensure that they are fit for purpose, and we can work more closely with civil society partners to inform and empower grassroots activists. Applying a “systems equity” perspective to the lessons we have learned from COVID-19 has changed how we think about and organize our activities and commitments, and it has helped us to articulate more explicitly the rationale for actions we had previously pursued only intuitively. In the year to come, we will be talking a lot more about our new Equitable Access Framework and its implementation plan.
Collectively, we are making progress. New international institutions are being established that will sustain and increase this momentum. I’ve already mentioned the Pandemic Fund, which was championed by Indonesia during its G20 presidency and stands as one of its chief accomplishments. The fund is woefully undercapitalized, but it establishes, for the first time, a joint financing mechanism to support pandemic preparedness and response. In December 2021, in only its second-ever special session, the World Health Assembly established an intergovernmental negotiating body to draft and negotiate a new convention (or so-called “Pandemic Treaty”) to strengthen pandemic prevention, preparedness and response. At the same time, a growing number of governments are establishing agencies dedicated to the development and production of medical countermeasures. Wellcome has set up an international Secretariat for the G7 to track progress against the 100 Days Mission, and Japan has retained the 100 Days Mission, now expanded to include manufacturing, as a key priority for its 2023 G7 presidency.
All of this is for the good, and important, but institutional change is slow. Fortunately, we are also seeing progress on the ground. The spread of mpox (previously known as monkeypox) to more than 100 countries this spring served as a reminder both of the potential for known diseases to surprise us and the value of prior investment in countermeasures. As it happens, the countermeasures we have – vaccines and antivirals against smallpox, which were developed and stockpiled because of concerns about bioterrorism – have the attribute of being pan-orthopoxvirus countermeasures, which means that we can use them against any orthopoxvirus: variola (the virus that causes smallpox), mpox, horsepox, mousepox, or any orthopoxvirus that emerges in the future. Having such tools available at the start of an outbreak is invaluable and changes the nature of the response, and their existence gives us a glimmer of what may be possible in the future against a broader array of viral threats.
Similarly, while we didn’t have countermeasures ready and stockpiled when the Sudan ebolavirus broke out in Uganda in September, they were in advanced stages of development. Several groups (the majority funded by our colleagues at the U.S. Biomedical Advanced Research and Development Authority, or BARDA) had brought Sudan vaccines and therapeutics to the point where they were ready for testing in the field. CEPI and a consortium of other funders joined WHO in supporting Uganda’s Ministry of Health and local investigators to accelerate the formulation of clinical trial material and adapt existing clinical trial protocols so that these products could be tested during the outbreak.
While it appears that the outbreak has been brought under control using traditional measures (isolation, contact tracing, and quarantine) and that such a trial now won’t be initiated, there is a tremendous amount we can learn much from this dry run. First, the fact that investigational products were delivered and ready to be deployed in early December, within about 70 days of the declaration of an outbreak, represents a new record for global response and a significant step towards achieving the 100 Days Mission. Second, the response reflected a new high-water mark for international cooperation and unity of purpose, with BARDA, CEPI, and the European Commission’s Health Emergency Preparedness and Response Authority (HERA) working well together in support of WHO and the Ugandan authorities. Third, all of the products that were deployed had been developed on existing platforms previously validated for other (and often related) diseases. Fourth, the set-up of the clinical trial in record time showed the value of having crack clinical trial teams poised and ready. The vaccine clinical trial team in Uganda, led by Dr. Bruce Kirenga, founding Director of the Makerere University Lung Institute, was poised and ready because they had just completed a number of clinical trials on COVID and knew exactly what needed to be done. Fifth, that the elements could come together so quickly, with local leadership, multilateral organizations, and international partners working together so effectively, was enabled by the Ministry of Health in Uganda’s reporting the outbreak promptly and its receptivity to international support.
These examples, particularly the latter, give me cause for hope at the end of a difficult year, when we are confronted by so many challenges and such huge problems – problems that at first seem beyond the power of individuals to influence, that seem to be sweeping us along in currents too powerful to resist. They validate our thinking and show that we are making progress towards our goals. And the work in Uganda demonstrates what can be accomplished through collaboration. The rapid progress there reflects a few committed individuals working together and across organizations for a common purpose, and it will become a benchmark for others.
The Reverend Martin Luther King famously said that “the arc of the moral universe is long, but it bends toward justice.” He borrowed that image and soaring language (with full attribution!) from a sermon, “Of Justice and the Conscience”, written by the 19th century Unitarian minister and abolitionist Theodore Parker. Parker, grappling with the enormities and injustice of his own era, ends that sermon which so inspired King with God-inflected language that can inspire us in our own efforts today, whatever our beliefs:
[I]n human affairs the justice of God must work by human means. Men are the measures of God’s principles; our morality the instrument of his justice, which stilleth alike the waves of the sea, the tumult of the people, and the oppressor’s brutal rage. Justice is the idea of God, the ideal of man, the rule of conduct writ in the nature of mankind. The ideal must become actual, God’s thought a human thing, made real in a reign of righteousness, and a kingdom — no, a Commonwealth — of justice on the earth. You and I can help forward that work. God will not disdain to use our prayers, our self-denial, and the little atoms of justice that personally belong to us, to establish his mighty work, — the development of mankind. You and I may work with Him, and, as on the floor of the Pacific Sea little insects lay the foundation of firm islands, slowly uprising from the tropic wave, so you and I in our daily life, in house, or field, or shop, obscurely faithful, may prepare the way for the republic of righteousness, the democracy of justice that is to come.
 I’m pleased to note that China’s National Medical Products Administration recently granted emergency use authorization to two vaccines that have received support from CEPI: Clover Biopharmaceuticals Ltd.’s recombinant subunit SCB-2019 (CpG 1018/Alum) and Hong Kong University’s nasally administered VectorFlu ONE (co-developed with Xiamen University and Wantai Biopharmaceutical Company). We hope that these vaccines, developed and produced in China, can contribute to easing China’s transition away from its Zero-COVID policy and reducing the impact of the disease on China’s 1.4 billion people, who account for one-sixth of the world’s population.
 Lancet Infect Dis 2022;222:1293-302.
 Along with Gavi, the Global Fund, and a number of other international institutions, CEPI has been pre-accredited as an implementing partner to help the Fund carry out its work.