COVID-19: From Crisis Management to Sustainable Solutions

Shared observations have been key to understanding a new problem

In France in late January 2020, five patients were diagnosed with infections caused by a new virus. Two of them were almost asymptomatic and made a rapid recovery. The condition of another two was initially reassuring before deteriorating after ten days and the fifth patient immediately developed a serious form of infection that led to multiple organ damage. These five patients were the first known cases in France of a novel coronavirus disease (Covid-19) caused by a severe acute respiratory syndrome (SARS). Since the first known epidemic of this type of coronavirus dated back to 2003, the new coronavirus was dubbed SARS-CoV-2.

SARS-CoV-2 was not known as an infectious agent in humans until January 2020, when it was identified as the causative agent of Covid-19, against which human beings had no natural immunity. Although six other coronaviruses that infect humans have been studied, including the coronavirus that causes the common cold, there was no known treatment or vaccine against SARS-CoV-2.

Since the first cases were described, over 4000 patients hospitalized across France for Covid-19 have been enrolled in an observational study (French Covid), with their willing participation, in order to improve our understanding of the disease, its symptoms and how patients respond to treatment. The data and information collected have been crucial in helping medical staff fight Covid-19.

In addition, biological samples collected from this observational cohort have been used in basic and clinical research. They have been used to study the genome of the virus, for example, and its interaction with the immune system. Such samples are valuable because the way in which the immune system responds to the virus varies widely from one individual to another. The majority of those infected with SARS-CoV-2 quickly recover. However, around 20% of infections require hospitalization and one-quarter of patients present severe forms of the disease. These cases generally involve acute respiratory insufficiency and, sometimes, thrombosis: blood clots form in the veins, reducing blood circulation and intensifying respiratory problems.

Rapid solutions relied on multinational adaptive trials

Without any known treatment to target the virus directly, health care professionals initially found themselves powerless to fight the disease.

In this type of health emergency, the most effective strategy in the early days is to repurpose existing drugs. The rapid spread of the disease from one country to another spurred a practical push for shared solutions. A European clinical trial known as the Discovery Trial was set up in record time.

Co-ordinated by the French National Institute of Health and Medical Research (INSERM), it began evaluating the efficacy of potential drugs against SARS-CoV-2 on 22 March 2020.

The Discovery Trial has been an integral part of Solidarity, the consortium grouping clinical trials that was announced by the World Health Organization (WHO) on 18 March 2020. As of 2 October 2020, this consortium grouped almost 12 000 patients from over 30 countries. The advantage of having such a consortium is that medical researchers participating in clinical trials use standardized methods to evaluate the same molecules, allowing international comparisons.

Solidarity and Discovery were designed as adaptive trials. The high level of adaptability of these studies makes it possible to adapt research protocols constantly, in order to incorporate the most recent and most robust international findings. In April 2021, discussions are under way with regard to testing new treatments.

In the fight against a viral disease, a vaccine is the most appropriate preventive treatment because it confers immunity to the virus. Although vaccine development is a gradual process that can take as long as a decade, the timeline has been compressed for Covid-19. Thanks to the rapid rallying of investment and previous knowledge of the infectious mechanisms of similar coronaviruses such as MERS-CoV and SARS-CoV-1 and immune responses to these, multiple projects for vaccine development could be launched within months of the publication of the SARS-CoV-2 genomic sequence in January 2020. Within a year, the first vaccines had been approved by the US Food and Drug Administration, the European Medicines Agency and other regulatory bodies and were already available in the market.

The pace of vaccine development and the longevity of vaccine effectiveness also depends on the biology of the virus. SARS-CoV-2 has a much lower mutation rate than the human immunodeficiency virus (HIV) or the influenza virus, for instance. However, as SARS-CoV-2 continues to replicate freely among the large segment of the population that is yet to be vaccinated, it is mutating. Several variants have emerged, some of which appear to be more virulent than the original form of the virus.

Vaccines are being developed to stimulate an immune response to a molecule found on the virus called an antigen. In the case of Covid-19, this antigen is the characteristic spike protein found on the surface of the virus which enables it to enter human cells. It is this protein that can trigger an immune response. Not surprisingly, it is this viral protein that has been targeted by most of the 182 vaccines listed by the World Health Organization at the end of 2020.

Four types of Covid-19 vaccine are being developed in clinical trials: whole virus, viral vector, protein subunit and nucleic acid [ribonucleic acid (RNA) and deoxyribonucleic acid (DNA)]. Whereas some vaccines try to smuggle the antigen into the body, others use the body's own cells to make the viral antigen. Nucleic acid vaccines take the latter approach; they use genetic material – either RNA or DNA – to instruct cells to make the antigen. The rapid development of this type of messenger mRNA vaccine against Covid-19 has been made possible by groundbreaking vaccine research in the early 1990s which targeted cancer immunotherapy. One challenge for RNA vaccines is that they need to be kept at temperatures of about -20°C, which necessitates specialized cold storage facilities.

Vaccines need syringes – and recipients

The preparation of vaccine options and even the large-scale production of enough vaccine doses to serve the population are insufficient in themselves to conquer a pandemic. In any outbreak, an effective prevention campaign also relies on the availability of materials, a trained workforce and the population's willingness to be vaccinated.

Many countries are grappling with their vulnerability to global value chains. They have made the disconcerting discovery that a surge in demand on the other side of the world can delay their own purchase of critical components needed to ensure a sustained medical response and vaccination effort over time. The surge in demand for drugs and personal protective equipment in the early days of the pandemic, for instance, led to shortages not only for medical staff but also for other branches of research relying on the same materials, such as laboratory gloves.

Some countries were able to call upon the private sector to address these shortages by approaching other suppliers or by enhancing their own production capacity using measures similar to those created in times of war like the repurposing of factory space. For example, Canada's Plan to Mobilize Industry to fight Covid-19, released in March 2020, required the country's five Innovation Superclusters involving public– private partnerships, as well as the Strategic Innovation Fund and the National Research Council, to prioritize funding and support for goods and services targeting the Covid-19 pandemic.

Mobilization improved by co-ordination

The Covid-19 crisis has demanded an unprecedented mobilization on the part of the international scientific community. Scientists have risen to the challenge, mobilizing across fields that span epidemiology, modelling, statistics, basic science and clinical research, as well as human and social sciences. This multidisciplinary approach to problem- solving has made it possible to guide decision-makers through the crisis. The objectives of this mobilization have been multifarious: to understand the disease, to improve its treatment, to develop vaccines rapidly and to anticipate future pandemic rebounds, in order to protect the population.

Around the world, research agencies and organizations have set up an array of newly funded research initiatives to tackle the crisis. In addition to national efforts, a number of international initiatives have been launched in key areas, such as vaccine development. In early 2020, the French Ministry of Higher Education, Research and Innovation began financing the effort by three INSERM units to develop second-generation vaccines against SARS-CoV-2. To this end, the INSERM teams have established contact with Sanofi and several other private biomedical companies.

A scramble for solutions can lead to quick results but also to duplication and wasted resources. To mitigate these concerns, French research institutions decided to form a consortium called REACTing in 2013 that has been co-ordinated by INSERM. REACTing has facilitated the provision of emergency seed funding for research from the Ministry for Solidarity and Health and the Ministry of Higher Education, Research and Innovation. It has also facilitated the fast-tracking of regulatory authorizations for clinical trials. It has been instrumental in collecting patient data and epidemiological information while co-ordinating national research efforts with other European countries.

REACTing has provided a link to funding mechanisms of the European Commission which have provided support for networks of national partners. The REACTing network has helped to identify a set of national research priorities based on those initially proposed by WHO. This has led to calls from various French research funding sources for projects that are expected to deliver results within 18 months. In 2020, 32 projects addressing Covid-19 were financed through the REACTing network for a total of € 1 775 000.

New agency to tackle emerging infectious diseases

Crisis management is temporary, by definition. To ensure that the French research and medical communities are better prepared to tackle the next emerging infectious disease, the government created a new research agency on 1 January 2021 by merging the Inserm-REACTing consortium with the French National Agency for Research on AIDS and Viral Hepatitis (ANRS). Going by the name of ANRS|Emerging Infectious Diseases, the new agency is responsible for facilitating, co-ordinating and funding French research on emerging infectious diseases. It enjoys great autonomy in terms of policy-making, priority-setting and budget management. Each year, the agency will launch calls for research proposals which, together with grant applications, will be reviewed by international advisory boards and scientific committees.

The new agency's research scope encompasses that of the two previous structures, addressing HIV/AIDS, viral hepatitis, sexually transmitted infections, tuberculosis and emerging infectious diseases, including emerging respiratory infections, viral hemorrhagic fevers and arbovirosis. The agency is active across a broad range of research disciplines: basic research, clinical research, public health research, epidemiology and social sciences. The new agency integrates the 'One Health' approach, addressing human and animal health, as well as the impact of human activities on the environment.

ANRS has previously sponsored hundreds of clinical trials to evaluate therapeutic strategies. Patient associations and civil society representatives will continue to play a key role in the new agency, with these ties being strengthened through the development of community-based research.

International collaboration is critical during a crisis

One priority of the new agency will be to strengthen collaboration with existing research platforms in low- and middle-income countries, particularly those directly affected by emerging infectious diseases. The research facilitated by the agency is intended to support national public health policies in these countries through the production of standardized research outputs. There are also plans to develop partnerships with national and international research institutes, universities and hospitals.

The new agency is also strengthening links with international public health organizations such as WHO, the European Commission, UNAIDS, the Global Fund to Fight AIDS, Tuberculosis and Malaria, Unitaid, the European and Developing Countries Clinical Trials Partnership, and the Global Research Collaboration for Infectious Disease Preparedness. The goal of such partnerships is to ensure optimal information exchange and to facilitate and accelerate the implementation of public policies based on scientific findings for the benefit of the global population as a whole.

A virus like SARS-CoV-2 will continue to spread – and mutate into potentially more threatening variants – until global immunity is achieved. This imperative has spurred the drive to ensure that as many people as possible around the world have access to immunization, supported by WHO's Covid-19 Vaccines Global Access Facility (Covax). International collaboration can serve national health interests: beyond the urgent need for immunization against Covid-19, the prevention of a future pandemic or, failing that, an effective response, could be driven by local research and monitoring capacity across the globe.

International collaboration is critical during a crisis but faces many obstacles, including geopolitical and economic considerations and the lack of harmonized standards for data- sharing and clinical trials. There is a need for effective new mechanisms to facilitate international collaboration and build trust among relevant national institutions.

Scientific research and public policies are mutually reinforcing

The current crisis has demonstrated the importance of science, including research, in leading the global response to crises (Akhvlediani et al., 2020). To build the foundations of an adequate response, research must be considered at its true value and financed in line with its ambitions. Research is an essential element before, during and after a crisis. Scientific research and public policies are mutually reinforcing. Scientific research provides evidence to inform and support decision-making and the implementation of public policies. In turn, policies that inform and support scientific institutions build resilience to future crises.

UNESCO SCIENCE REPORT

The race against time for smarter development

It is striking how development priorities have aligned over the past five years. Countries of all income levels are prioritizing their transition to digital and 'green' economies, in parallel. This dual transition reflects a double imperative. On the one hand, the clock is ticking for countries to reach their Sustainable Development Goals by 2030. On the other, countries are convinced that their future economic competitiveness will depend upon how quickly they transition to digital societies. The UNESCO Science Report's subtitle, 'the race against time for smarter development', is an allusion to these twin priorities.

This seventh edition of the report monitors the development path that countries have been following over the past five years from the perspective of science governance. It documents the rapid societal transformation under way, which offers new opportunities for social and economic experimentation but also risks exacerbating social inequalities, unless safeguards are put in place.

The report concludes that countries will need to invest more in research and innovation, if they are to succeed in their dual digital and green transition. More than 30 countries have already raised their research spending since 2014, in line with their commitment to the Sustainable Development Goals. Despite this progress, eight out of ten countries still devote less than 1% of GDP to research, perpetuating their dependence on foreign technologies.

Since the private sector will need to drive much of this dual green and digital transition, governments have been striving to make it easier for the private sector to innovate through novel policy instruments such as digital innovation hubs where companies can 'test before they invest' in digital technologies. Some governments are also seeking to improve the status of researchers through pay rises and other means. The global researcher population has surged since 2014.

The Covid-19 pandemic has energized knowledge production systems. This dynamic builds on the trend towards greater international scientific collaboration, which bodes well for tackling this and other global challenges such as climate change and biodiversity loss. However, sustainability science is not yet mainstream in academic publishing, according to a new UNESCO study, even though countries are investing more than before in green technologies.

Source: Eric D'Ortenzio, Evelyne Jouvin Marche, Oriane Puéchal, Inmaculada Ortega Perez, and Yazdan Yazdanpanah, https://unesdoc.unesco.org/ark:/48223/pf0000377446
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