Implementation of the federal genomic surveillance platform for SARS-CoV-2

Published on June 01, 2021, by Simon Dellicour & Guy Baele


The continuing accumulation of SARS-CoV-2 infections across the world continues to pose a significant threat to public health, with the different variants of concern (VOCs) being the primary focus, especially those that originated in South Africa (lineage B.1.351) and Brazil (lineage P.1) due to their potential of escaping vaccine-induced immunity, a pressing concern now that vaccination campaigns are being deployed around the world. Additionally, many countries are trying to avoid or control a next wave of infections by maintaining public health measures (including social distancing and partial or complete lockdowns) to avoid flooding hospitals with patients and to keep medical care facilities from collapsing.

In order to monitor the evolution and spread of the different SARS-CoV-2 variants at the national level, Belgium has rapidly scaled up its genomic surveillance efforts since the start of 2021, following the emergence of the first SARS-CoV-2 VOC 202012/01 cases (lineage B.1.1.7) at the end of November, 2020. Based on the total available data on GISAID/ECDC databases on May 14, 2021, Belgium has currently ramped up its genomic coverage from 0.5% (before 2021) to nearly 3% of positive cases since the start of 2021, leading to a total of 19,787 sequenced SARS-CoV-2 genomes (16,849 submitted since the start of 2021). These efforts also serve to monitor the relative proportion and spread of specific mutations (e.g. N501Y, HV 69-70 del, E484K, K417N/T [1]) and the three VOCs currently circulating in the country. In order to attain such a national initiative, a coordinated sequencing and surveillance strategy has been jointly set up that includes sequencing centers at major universities who committed to substantially scale up their capacity, along with an increasing number of hospitals throughout the country, totaling 17 centers. Samples are collected through a country-wide network of 26 sentinel PCR laboratories, which ensure a wide geographic coverage including community, first line care and hospitals in all provinces. These samples are sent to one of the sequencing centers, which are responsible for making the sequences publicly available through GISAID [2]. These are used to update both global and Belgium-focused analyses and visualisation tools (e.g. Nextstrain [3]) and to inform public health authorities weekly on the circulation and projected short-term trends of different variants of the virus and the possible emergence of potentially more transmissible, virulent, or vaccine-escaping strains [4]. These reports constitute a documented and publicly available source of information, which is used by authorities together with other epidemiological reports to decide on the most suitable panel of public health interventions.

At the time of writing, VOCs constitute nearly 95% of all infections in Belgium during the last two weeks. As of the start of April, B.1.1.7 represents 85.9%, B.1.351 3.7%, and P.1 4.9% of all infections, with these numbers having increased from respectively 63.7%, 9.3%, and 3.9% since the start of March. From the data, it is evident that lineage B.1.1.7 is keeping the other VOCs at bay and is doing so at an increasing level. Despite the concerns associated with lineages B.1.351 and P.1 regarding their potential of escaping vaccine-induced immunity, a recent study found that B.1.1.7 is not only more transmissible than preexisting SARS-CoV-2 variants but may also cause more severe illness, including death [5].

Belgium is now witnessing a slowly decreasing level of new infections and intensive care unit occupation, with the situation currently at a tipping point due to the easement of preventative measures since May 8, 2021, involving carefully monitored reopening of outdoor restaurants and allowing outdoor cultural events for groups of fifty individuals. Further relaxation of measures is currently planned for the 9th of June, conditional on vaccination coverage and hospital occupancy. Current news that as of August 13 music festivals will receive an exception to the maximum limit of 5,000 people on outdoor events has left virologists and healthcare personnel in disbelief, with one festival announcing plans to operate at full capacity of 66,000 during its four consecutive event days. Attendants will have to be either tested or vaccinated, but will not have to wear a mask or adhere to any form of social distancing.

Besides performing baseline surveillance, the Belgian government has also requested that immediate action be taken to obtain and sequence samples in large outbreak centers, such as in elderly care facilities, which - along with healthcare personnel - form the first major group targeted by the national vaccination program. The current goal is to administer a first vaccine dose to seventy percent of Belgium’s population by the end of summer of 2021. During this time (and afterwards), the aforementioned genome surveillance will be essential to monitor any alteration of lineage circulation and the possible emergence of VOCs, or other strains with immune-escape mutations, that may elude vaccine-induced immunity. To this date, at least fifteen post-vaccination outbreaks (i.e. occurring at least seven days after full vaccination) have been detected, the majority caused by B.1.1.7, two by B.1.351, one by B.1.214.2, one by P.1 and one by a combination of both B.1.617.1 and B.1.617.2. Genome sequencing is currently ongoing for other potential post-vaccination outbreaks.

This genomic surveillance program has enabled Belgium to detect a wide range of variants, other than the VOCs, such as B.1.214.2, B.1.525, as well as B.1.617.1 and B.1.617.2 (i.e. the variants first identified in India). B.1.214.2 saw a rapid increase in cases, leading to nearly 500 sequenced samples in Belgium, and continues to be found in seemingly increasing numbers. Of particular concern are the latter two variants, which are currently being reported as wreaking havoc in India and are reported as being responsible for the massive surge in infections, which is causing a collapse in the local healthcare system with reported shortages in hospital beds and oxygen for patients. B.1.617.2 was designated as VOC in the United Kingdom on May 6, 2021, after a quick rise in the number of infections since the beginning of April 20216. Belgian laboratories have now sequenced and made publicly available six B.1.617.1 and forty-five B.1.617.2 genomes. The first B.1.617.1 patients are located in the Brussels Capital Region and in the region around the city of Antwerp, making it unlikely to establish a link to a single source of introduction of infections entering the country at the end of March 2021. The same pattern emerged for the first B.1.617.2 infections in the first two weeks of April 2021, with patients located in the Brussels Capital Region and in the region around the city of Ghent. So far, mild disease symptoms are being reported for most of the infected individuals, even in the presence of underlying health issues, with no hospital admission being required. Currently, there are outbreaks being reported in a nursing home, with one fully vaccinated inhabitant having passed away. As additional infections are being reported at the time of writing, the variant responsible for these infections still needs to be determined by the genomic sequencing partners in our consortium. The genomic surveillance efforts reported here aim to closely monitor the situation and inform the government of appropriate action, as more data are surely to surface regarding infectiousness and disease severity.

Non-exhaustive list of collaborators working for the genomic surveillance consortium: Barney Potter, Samuel Hong, Jasper Wolfs, Sebastiaan Theuns, Bruno Verhasselt, Linos Vandekerckhove, Laurens Lambrechts, Nick Vereecke, Sofieke Klamer, Nathalie Bossuyt, Herman Goossens, Lize Cuypers, Mandy Bloemen, Tony Wawina-Bokalanga, Bert Vanmechelen, Joan Martí-Carreras, Marc Van Ranst, Keith Durkin, Maria Artesi, Vincent Bours, Piet Maes, Emmanuel André

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  2. Shu Y, McCauley J (2017). GISAID: Global initiative on sharing all influenza data – from vision to reality. Eurosurveillance 22: 30494

  3. Hadfield J, Megill C, Bell SM et al. (2018). Nextstrain: real-time tracking of pathogen evolution. Bioinformatics 34: 4121–4123

  4. Martin MA, VanInsberghe D, Koelle K (2021). Insights from SARS-CoV-2 sequences. Science 371: 466–467

  5. Davies NG, Jarvis CI, Edmunds WJ, Jewell NP, Diaz-Ordaz K, Keogh RH (2021). Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature 593: 270–274

  6. Public Health England (2021). SARS-CoV-2 variants of concern and variants under investigation. Technical Briefing 10: 39