SEQ4EPI Project

Call for Proposals: Enhancing national infrastructures and capacities for whole genome sequencing (WGS) and/or reverse transcription polymerase chain reaction (RT-PCR) to respond to the COVID-19 pandemic and future health threats.

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Since 2022, the response to the COVID-19 pandemic has gradually moved beyond the realm of exceptional crisis management and is becoming more routine. To this end, the surveillance systems established during the crisis—including those for monitoring SARS-CoV-2 variants—must be integrated into existing structures and prepared for future emergencies by adapting to other pathogens.

Funding Source

As part of the EU4HEALTH program, the European Commission launched a new call for projects in April 2022, through its executive agency HaDEA, targeting countries that had previously received funding from the ECDC. This call for proposals aimed to consolidate the development of recently established WGS and/or RT-PCR infrastructures, integrate them into routine activities, and ultimately make them a fully integrated component of national public health systems.

Project Objectives: SEQ4EPI (Pathogen Sequencing for Epidemiology)

The SEQ4EPI project, led by Santé publique France and the CNR Virus des Infections Respiratoires, aims to support the sustainability of genomic surveillance systems established during the pandemic and prepare them for future crises by strengthening genomic surveillance activities in various areas (expansion to other pathogens, development of genomic analysis tools, strengthening of epidemiological analysis capabilities) over a three-year period (October 1, 2022 – September 30, 2025). The objectives of the SEQ4EPI project are therefore divided into two phases:

  • in 2022–2024, the establishment of sustainable SARS-CoV-2 genomic surveillance and its integration into routine activities;

  • in 2023–2025, the gradual expansion of the systems established for SARS-CoV-2 to other pathogens with high emerging potential. This expansion will begin with other respiratory viruses (influenza, RSV) but will not be limited to them.

The activities planned under the SEQ4EPI project aim to:

  • strengthen Santé publique France’s coordination activities to consolidate existing genomic surveillance efforts established for SARS-CoV-2 and gradually extend them to other emerging pathogens, including other respiratory viruses;

  • define and implement analytical tools to better monitor viral epidemics—for SARS-CoV-2 and other viruses—based on bioinformatics, phylogenetic, and phylodynamic techniques;

  • maintain a team of epidemiologists at the national and regional levels to investigate signals, coordinate the laboratory network, and conduct risk analysis.

Actions taken as of March 31, 2024

The SEQ4EPI project is part of the broader activities of the EMERGEN consortium, covering its surveillance and public health aspects. Coordination within the EMERGEN consortium is therefore essential to the success of the SEQ4EPI project’s objectives. For example, the EMERGEN-DB database, managed by the consortium, is essential for the surveillance of SARS-CoV-2 variants, and Santé publique France staff working on the project have been involved in its development.

The primary objective of the SEQ4EPI project was to strengthen the existing SARS-CoV-2 genomic surveillance activities carried out by Santé publique France. These activities are intended to be gradually expanded to other infectious diseases with the potential to emerge. A survey was conducted among the CNRs to better understand the organization of their sequencing activities, the methods used, and the genomic surveillance needs for the pathogens included in their mandates.

The adaptation of the SARS-CoV-2 genomic surveillance strategy to changes in the epidemiological situation has been the subject of several reports, such as the one on the various sampling strategies for maintaining effective monitoring of SARS-CoV-2 variants, whose recommendations have since been implemented. Additional work is underway with the CNR Virus des Infections Respiratoires to continue the transition from a COVID-19 crisis response model to more sustainable surveillance approaches. The results of SARS-CoV-2 variant surveillance have been included in regular publications dedicated to COVID-19, which have evolved into integrated surveillance of acute respiratory infections (ARI), with 35 COVID-19 bulletins and 26 ARI bulletins published on our website since the project’s inception in October 2022.

Regarding the EMERGEN-DB database, a joint service unit responsible for its maintenance and development was created at INSERM. This database is essential to the activities of the SEQ4EPI project. Santé publique France monitored and supported this transfer to ensure the continued accessibility of these data and the maintenance of operations tailored to the needs of public health stakeholders, including Santé publique France, the CNRs, and ANSES.

The SEQ4EPI project is part of broader efforts to ensure the sustainability of the EMERGEN consortium after the pandemic ends. A new consortium agreement for EMERGEN 2.0 is currently being drafted. Discussions have been initiated with ANSES to strengthen EMERGEN’s OneHealth focus. A new working group has been created within the SUM’Eau initiative for detecting SARS-CoV-2 in wastewater to study the public health benefits of sequencing in wastewater.

The second objective of SEQ4EPI is to develop analytical tools for tracking the circulation dynamics of SARS-CoV-2 and other viruses using bioinformatics, phylogenetics, and phylodynamics.

The CNR Respiratory Infections Virus Unit has developed bioinformatics methods for the early detection of SARS-CoV-2 variants carrying mutations that could affect virus detection; these methods are used routinely and have been refined over time. This tool detects mutations that may affect the recognition of the virus by primers and probes, enabling real-time monitoring of the robustness of RT-qPCR detection tests. To do this, it compares the sequences of these primers and probes with all circulating genomes and assigns a score based on the mutations present at the primer-probe interaction site. The scores thus assigned make it possible to assess the impact of mutations on the sensitivity of RT-qPCR tests. A similar tool to assess escape from sequencing methods is currently under development.

In parallel, the CNR Virus des Infections Respiratoires is working on the detection of potential clusters based on SARS-CoV-2 sequences. This tool combines phylogenetics (analysis of genomic data) and metadata (location, date, etc.) to reconstruct potential transmission chains. Genomic and phylogenetic data can also be used to determine epidemiological parameters (such as the reproduction number R) using phylodynamic models (e.g., Beast).

The third objective of SEQ4EPI is to ensure the availability of the necessary human resources (epidemiologists at Santé publique France) at the national and regional levels for signal investigation, coordination of laboratory networks, and risk analysis. These epidemiologists meet every two weeks to coordinate ongoing activities, in addition to ongoing communication. During the first 18 months of the project, activities shifted from primarily routine surveillance—which represented a significant workload for regional and national teams—to prospective projects.

The teams of epidemiologists at Santé publique France are responsible for monitoring SARS-CoV-2 variants, specifically:

  1. organizing weekly Flash surveys,

  2. providing feedback to laboratories through the distribution of 137 regional EMERGEN bulletins,

  3. monitoring surveillance data and identifying signals,

  4. reporting results in weekly epidemiological bulletins and preparing 18 risk assessments. A working group proposed a new format for these risk assessments, which has been in use since March 2024.

Following the emergence of the BA.2.86 variant in August 2023, investigations into cases of infection with this variant were conducted to assess its characteristics and evaluate its public health impact. More than 200 cases were reported to epidemiologists in the regional units, and 147 of them were interviewed using a standardized questionnaire. The results of these investigations were published in the risk analysis of December 11, 2023, and included in a scientific publication (currently being finalized).