The goal of SARS-CoV-2 genomic surveillance in France and around the world is to track the spread of different SARS-CoV-2 variants and detect the emergence of new variants that could alter the dynamics of the COVID-19 pandemic; it relies in particular on the sequencing of a representative sample of RT-PCR-positive specimens. Since its establishment in January 2021, the Emergen consortium, coordinated by Santé publique France and ANRS|Emerging Infectious Diseases (MIE), has mobilized several public medical virology platforms with strong sequencing capabilities and a network of hospital virology laboratories coordinated by ANRS|MIE, and to develop an infrastructure enabling the use of these sequences for surveillance and research purposes. A call for expressions of interest also made it possible, at the height of the crisis, to further increase these sequencing capacities by engaging four private platforms.

After two years of operation and efforts—which notably led to the production of more than 700,000 sequences by the consortium’s laboratories—the needs for SARS-CoV-2 genomic surveillance have evolved: the consortium’s activities continue but must therefore adapt.

How is SARS-CoV-2 genomic surveillance evolving?

Since January 1, 2023, genomic surveillance of SARS-CoV-2 variants has evolved, with sequencing activities now centered around the CNR Respiratory Infections Virus, in close collaboration with clinical laboratories collecting samples and with the support of hospital laboratories in the ANRS|MIE network.

The volume of samples to be sequenced for surveillance purposes (Flash surveys) is assessed weekly based on the number of positive cases in the general population, in accordance with European recommendations. Based on these recommendations, a weekly volume of between 2,000 and 3,000 sequences now makes it possible to detect any new emerging variants and track their spread appropriately. In addition, sequencing continues for other indications (severe cases of COVID-19, immunocompromised patients, etc.).

Thus, Flash surveys continue on a weekly basis, and all sequences generated continue to be centralized on the EMERGEN-DB platform. The resulting analyses are published on the Santé publique France website via the InfoCovidFrance dashboard and the weekly epidemiological update. These sequences are also shared internationally via the GISAID database. Based on these data, a risk analysis is produced at least once a month by Santé publique France and the CNR Virus des infections respiratoires: it details the situation and characteristics of circulating variants and their potential impact (vaccine escape, transmissibility, etc.). Ongoing efforts to monitor sampling and specimen workflows enable this surveillance system to meet its objectives in terms of volume, geographic distribution, and turnaround times.

National sequencing capacities are currently sufficient to enable teams at Santé publique France and the National Reference Center for Respiratory Infections to address the challenges of monitoring SARS-CoV-2 variants at the national and international levels. These capacities also allow them to expand their sequencing activities to other respiratory viruses (influenza, RSV infections). In addition, the capabilities of the ANRS|MIE network remain available for more targeted sequencing needs (severe cases, immunocompromised patients, etc.) should these requirements change again.

3 questions for Bruno Coignard, Director of Infectious Diseases at Santé publique France

Why did the restructuring of Emergen take place on December 31, 2022?

The evolution and restructuring of sequencing activities within the Emergen consortium, which took effect on January 1, 2023, were planned. They are primarily linked to a reassessment of needs in light of the evolving COVID-19 pandemic—a reassessment conducted across all participating countries, in Europe in accordance with ECDC recommendations. They are also linked to changes in the legal framework concerning certain platforms. Thus, the 2017–2022 mandate of the CNR network has ended, and this network was renewed on January 1, 2023, for five years (2023–2027), following a call for applications conducted in 2021–22. In this context, we now have a new CNR for Respiratory Infectious Viruses, coordinated by the Hospices Civils de Lyon (HCL), which has partnered with three other laboratories: the Institut Pasteur (Paris), the Institut Pasteur de la Guyane, and the University Hospital of La Réunion. The two CNR-expert laboratories supporting SARS-CoV-2 sequencing (Henri Mondor Hospital and Assistance publique – Marseille Hospitals) were not renewed under this call for applications, but their capabilities remain in place and accessible via the ANRS-MIE network. Furthermore, the mandate of the private platforms designated following a call for expressions of interest in 2021 was also set to expire on December 31, 2022. These developments therefore had to be taken into account.

What is the current sequencing capacity in France?

It is currently estimated that we can monitor the emergence and circulation of different SARS-CoV-2 variants across France with a number of sequences ranging, depending on the week, between 2,000 and 3,000. This is the level of activity we are maintaining today. Other sequencing activities complement this “core” work: targeted sequencing for severe cases of COVID-19 or in immunocompromised patients, and intervention sequencing when investigating clusters, or other newly identified needs, such as sequencing travelers returning from China, for example.

Today, the consortium’s capacity (which relies on that of the CNR and the ANRS | MIE network) is approximately 10,000 sequences per week, including 4,000 from the CNR’s metropolitan laboratories (HCL and Institut Pasteur) alone. This allows us to meet these needs and maintain reserve capacity. Since we need approximately 2,000 to 3,000 sequences per week to effectively monitor variants through Flash surveys, we have refocused this activity on the CNR, in line with its mission to contribute to surveillance. This does not mean, however, that the CNR works alone: its activities are carried out in close collaboration with a network of public and private clinical laboratories.

It also means that the CNR has spare capacity that will now also serve us for other challenges, particularly those posed by other respiratory viruses (Influenza viruses responsible for the flu, respiratory syncytial virus—RSV—responsible for bronchiolitis). The CNR’s sequencing activities for influenza viruses have a long history, and it has contributed to the genomic surveillance of influenza viruses at the international level for many years, notably as a WHO collaborating center; this activity will continue and expand. Like Santé publique France for epidemiological surveillance, the CNR integrates its genomic surveillance activities into a comprehensive approach that now encompasses all acute respiratory infections.

What are the future prospects and challenges for EMERGEN?

EMERGEN is in a transition phase, as part of the “normalization” of COVID-19, and this is also the case for other European consortia. The infrastructure is being maintained (in particular the EMERGEN-DB database, which enables the centralization and sharing of these sequences), and while genomic surveillance activities are refocusing on public health laboratories (the CNR network in France), collaborations with all medical biology laboratories—both public and private—and with the research community must be maintained and even strengthened, as they have proven their value during the crisis. In particular, this involves continuing to bring together a community of institutions and professionals who have learned to work together, have made a tremendous commitment, and have contributed significantly to addressing the many questions raised by this pandemic. In this context, and in close collaboration with ANRS|MIE, Santé publique France is maintaining the necessary surveillance and research activities on COVID-19 and aims to extend them to other viruses likely to cause future outbreaks and potential pandemics, starting with respiratory viruses. The challenge today is to transition from an organization built during a crisis to a sustainable and more robust organization capable of better anticipating and responding to future health crises.