Project to Enhance 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
Learn all about the project, its objectives, and the actions being taken as part of the European Biodefense Preparedness Plan against coronavirus variants.
To strengthen national capabilities for genomic surveillance of SARS-CoV-2, Santé publique France and certain partners in the EMERGEN consortium (Institut Pasteur, Hospices Civils de Lyon, APHP-Mondor, APHM, Institut Français de Bio-informatique/CNRS) and the university hospitals of Martinique and Réunion responded to a European call for proposals.
Mission: Strengthening national infrastructure and capabilities for whole-genome sequencing and/or RT-PCR in response to COVID-19
Source of funding
In late 2020, the European Commission proposed the creation of a European Health Emergency Preparedness and Response Authority (HERA) to enable Member States to rapidly deploy medical measures and thereby ensure their capacity to respond to cross-border threats and emergencies. In anticipation of HERA’s official establishment, several preparatory actions—intended to be ultimately carried out by this new authority—were initiated. One of these was the reactive detection of SARS-CoV-2 variants, which was the subject of an ECDC call for proposals titled: “Enhancing Whole Genome Sequencing (WGS) and/or Reverse Transcription Polymerase Chain Reaction (RT-PCR) national infrastructures and capacities to respond to the COVID-19 pandemic.” The objectives of this call for proposals were:
In the short term: to contribute to the establishment of sustainable, effective whole-genome sequencing and/or RT-PCR infrastructures with significant capacity;
In the short to medium term: to contribute to the early detection and enhanced monitoring of known or emerging SARS-CoV-2 variants at the national and European levels;
in the medium/long term: to strengthen genomic investigation capabilities for infectious diseases at the regional, national, and European levels;
Medium/long term: Strengthen genomic surveillance capabilities for infectious diseases at the regional, national, and European levels and integrate molecular typing into surveillance and investigation strategies;
Long term: contribute to preparedness for future international epidemics
Project Objectives
The project proposed by Santé publique France pursued the following objectives over a one-year period (September 3, 2021 – September 30, 2022):
Improve the quality of SARS-CoV-2 sequencing data in the network’s laboratories through external quality assessment.
Strengthen SARS-CoV-2 sequencing capabilities in the French overseas departments and regions (DROM) to enable more responsive sequencing when needed.
Develop network coordination and investigations at the national and regional levels.
Establishment of a rapid sequencing pathway to reduce sequencing turnaround times in specific cases requiring greater responsiveness.
Actions Taken
An independent EQA was coordinated by the laboratory affiliated with the National Reference Center for Respiratory Virus Infections (Hospices Civils de Lyon) in collaboration with QCMD (Quality Control for Molecular Diagnostics), the French Institute of Bioinformatics (IFB), the Swiss Institute of Bioinformatics (SIB), and Santé publique France.
Forty-eight sequencing laboratories from the consortium performing whole-genome sequencing participated in this exercise.
The first phase of the EQA aimed to assess the participating laboratories’ ability to produce high-quality sequences and assign a SARS-CoV-2 lineage to them. The second phase of the EQA focused on detecting complex situations such as co-infections or recombinants. Aggregated and anonymized results were shared with all partners, and confidential individual results were sent to each participating laboratory.
Given their geographical location, the circulation of SARS-CoV-2 variants in the French overseas departments and regions (DROM) is the subject of particular attention. Local SARS-CoV-2 sequencing capabilities in the French overseas departments and regions (DROM) eliminate the need to wait for samples to be sent to mainland France and allow for more responsive monitoring of the variants circulating there. For this reason, the HERA project has enabled the acquisition of new equipment for the university hospitals in Martinique and Réunion (sequencers, laboratory equipment, and IT systems).
To strengthen the regional presence of sequencing activities, a network of 17 regional coordinators worked to strengthen ties with primary care laboratories (to ensure the smooth flow of samples for sequencing), sequencing laboratories, and regional health agencies.
This work helped streamline the flow of samples for sequencing and facilitated the identification, communication, and management of alerts related to SARS-CoV-2 variants. This network was particularly valuable for investigating emerging variants whose characteristics were still poorly understood, including B.1.640 in Brittany in the fall of 2021 [1], Omicron upon its emergence in late 2021 [2], the Delta/Omicron XD recombinant in early 2022 [3], and BA.4/BA.5 in the spring of 2022 [4]. The results of these investigations were shared early on in the COVID-19 epidemiological updates and variant risk analyses to inform decision-making.
At the same time, a working group was launched with the aim of improving the quality of metadata submitted to the EMERGEN-DB sequencing database. It brought together Santé publique France, the CNR Virus des Infections Respiratoires, and the Institut Français de Bio-informatique. This group then worked on a sequencing activity dashboard and on the automatic submission of EMERGEN-DB data to the international GISAID database.
[1] www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.6.2200078">https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2023.28.22.2200671 and www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.6.2200078">www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.6.2200078
[2] ">https://www.sciencedirect.com/science/article/pii/S2666991922000367?via=ihub
[3] https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac360/6583149?login=true
">https://www.researchsquare.com/article/rs-1502293/v1 and https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac360/6583149?login=true
">https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac360/6583149?login=true
[4] https://www.frontiersin.org/articles/10.3389/fpubh.2022.1006631/full
Most sequencing techniques require a certain amount of time for sample receipt, preparation, and sequencing. In certain very specific cases, faster results may be necessary. For this reason, a so-called “rapid” sequencing pathway has been established. Sequencing laboratories participating in this pathway commit to delivering results within 48 hours of receiving the sample. However, this pathway can only be activated in very specific situations where a sequencing result is necessary for decision-making and always with the prior approval of the sequencing laboratory.
To make this rapid sequencing feasible, four partners in the HERA project have been equipped with Nanopore sequencing technology (which allows for sequencing smaller sample volumes but with shorter turnaround times) and IT equipment for storing and managing these sequences. These include two laboratories from the CNR Virus des Infections Respiratoires (Institut Pasteur and Hospices Civiles de Lyon), the APHP – Henri Mondor, and the AP-HM.
Project Completion
The project concluded in October 2022. It helped improve the quality, representativeness, and utilization of SARS-CoV-2 sequencing for public health. The equipment acquired through this project, along with the establishment of a network of stakeholders with expertise in genomics, continues to support SARS-CoV-2 genomic surveillance in France today.
