Pandemic preparedness to Respiratory Virus X: integrative modelling from first cases to early public health countermeasures

"In 2020, a new coronavirus plunged the world into one of its most dramatic health crises in just a few months. Caught short on the health, political, and scientific fronts like many other countries, France was forced to impose measures on an unprecedented scale to preserve its healthcare system. The succession of SARS-CoV-2 (sub-)variants since 2021 and the intense circulation of avian influenza in 2024 have made cross-sectoral preparedness for future respiratory virus threats an international priority. In this context, the World Health Organization (WHO) renewed in 2022 its list of priority pathogens to be targeted by adding Disease X, caused by "an unknown pathogen likely to cause a serious international epidemic". By mentioning a yet unidentified threat, the WHO urged the international community to broaden scientific research to yet undocumented pathogen species and strains, to prepare for the next pandemic - which is likely to be caused by a new respiratory virus. To this end, we urgently need innovative models and research protocols readily implementable at the onset of such an outbreak to inform in real time all health actors and authorities with robust analyses, nowcasting and projections. The PReViX project will develop an actionable research and sanitary framework for Respiratory virus that addresses the WHO incentives. It takes advantage of the scientific corpus and operational experience gained with the influenza or coronavirus outbreaks and pandemics of the last two decades. This project is organised into six work packages, each employing quantitative approaches tailored for the challenges ahead regarding the diversity of data sources, as well as their real-time analysis and the support of emergency health decision-making. These work packages will make it possible to establish the microbiological, infectious, and epidemiological contours of future respiratory virus threats while proposing innovative methods to monitor, characterise, model in real time and intervene on the early spread of a (re-)emerging respiratory virus, based on the first available data, heterogeneous both in terms of nature and quality. Main challenges include 1) the early assessment of the pandemic and health crisis potential of the respiratory virus, compared to previous epidemics, 2) the use of within-host viral-immune dynamics to inform vaccine target profiles and testing policies, 3) the development of more performant and accessible tools to exploit viral genomic sequences, 4) a better characterization of antibody dynamics and the improvement of epidemic forecast from antigenic data, 5) the design of early strategies for non-pharmaceutical interventions and 6) for the healthcare system to cope with future epidemics depending on their characteristics. This project is led by a national consortium of 9 research units spread over 4 sites with interdisciplinary expertise covering the fields of epidemiology and modelling of infectious diseases, public health, phylogenomics, virology, infectiology, behavioural and social sciences, and having produced several major results during the COVID-19 pandemic. It will help consolidate the French research community in quantitative approaches in infectious disease research. This will result in world-class scientific results as well as in the production, in close collaboration with the main public health actors in France, of decisive risk assessments for future respiratory virus epidemics. By catalysing the emergence of the next generation of interdisciplinary researchers in infectious diseases throughout the country, while consolidating interactions between public research, health agencies and decision-makers around the anticipation of a yet undetermined pandemic respiratory virus, this project aims to contribute, scientifically and beyond, to the country's preparedness for future outbreaks and health crises."