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Circulation of variants: a new screening strategy based on the identification of mutations of interest

Given the diversity of emerging SARS-CoV-2 variants, the initial screening strategy targeting variants of concern VOC 20I/501Y.V1 (Alpha), VOC 20H/501Y.V2 (Beta), and 20J/501Y.V3 (Gamma) is evolving into a new screening strategy to identify mutations of interest. New indicators shared as open data will soon be available.

Coronavirus: Circulation of SARS-CoV-2 Variants

Many variants of SARS-CoV-2 are circulating in France, and new variants carrying mutations are regularly identified. How are they monitored and classified? Learn all about the...

The variant surveillance conducted by Santé publique France is based on:

  • a comprehensive strategy that includes screening of positive test results to enable reactive detection of known variants of concern (VOCs),

  • mapping of virus types circulating in France and the detection of new variants via sequencing,

  • enhanced epidemiological surveillance to identify any epidemiological signals (such as an increase in incidence) that could serve as a warning, given the strong suspicion of increased transmissibility of these new variants.

Mutations are an expected phenomenon and appear to impact immune escape or the virus’s transmissibility. As the epidemic and our understanding evolve, the screening strategy adapts to ensure greater precision and efficiency.

Why monitor mutations rather than variants?

The screening tests used until now allowed for the distinction of the 20I/501Y.V1 (Alpha) variant but did not distinguish between the 20H/501Y.V2 (Beta) or 20J/501Y.V3 (Gamma) variants. Given the growing diversity of emerging SARS-CoV-2 variants, this screening strategy must evolve.

Thus, the evolution of the screening strategy no longer involves assigning the infection to a specific variant but rather searching for mutations of interest. Currently, three of these are classified as mutations of interest: E484K, E484Q, and L452R. They are monitored using new screening techniques developed to identify them, and the results are integrated according to a new specific nomenclature for each of the three selected mutations. This new nomenclature will make it possible to track changes in the proportion of infections caused by a virus carrying these mutations over time and across the country.

The E484K, E484Q, and L452R mutations were selected because they are associated with a possible increase in transmissibility (L452R) or potential immune escape (L452R, E484K, and E484Q). If new mutations were found to be associated with this type of impact on the virus’s transmissibility, it might then be necessary to include them in new screening kits.

This strategy is accompanied by updates to the SI-DEP database, with the adoption of specific nomenclature for each of the three selected mutations.

Table – Available information on the E484K, E484Q, and L452R mutations or the variants carrying them (excerpt from the risk analysis of 06/02/21)

Mutation Date of first sequence in GISAID Variants carrying the mutation Impact of the mutation
E484K

Internationally: 04/16/2020

In France: 11/12/2020

VOC 20H/501Y.V2 (B.1.351, Beta) VOC 20J/501Y.V3 (P.1, Gamma) VOC 20I/484K (B.1.1.7+E484K) VOI 20C/484K (B.1.526, Iota) VOI 20A/484K (B.1.525, Eta) VOI 20B/681H (B.1.1.318)
VUM 20C/452R (B.1.526.1)
VUM 20A/440K (B.1.619)
VUM 20A/477N (B.1.620)
VUM 20B/484K (P.2, Zeta)

Extensive in vitro data:
- Decreased efficacy of the neutralizing humoral response (post-infection, post-vaccination, and monoclonal antibodies)

Epidemiological data:
- Increase in the number of variants carrying this mutation
- Increase in the detection of this mutation internationally (10% of total sequences deposited in GISAID and collected between April 1, 2021, and June 1, 2020)

E484Q

Internationally: March 9, 2020

In France: 02/21/2021

VOC 20I/484Q (B.1.1.7+E484Q) VOI 21A/154K (B.1.617.1, Kappa)

Very limited in vitro data:
- Hypothetical impact on the efficacy of the neutralizing humoral response, not demonstrated

Epidemiological data:
- Limited number of variants carrying this mutation
- Low detection of this mutation internationally (0.3% of total sequences deposited in GISAID and collected between 04/01/2021 and 06/01/2020)

L452R

Internationally: March 17, 2020

In France: 10/15/2020

VOC 21A/478K (B.1.617.2, Delta) VOI 21A/154K (B.1.617.1, Kappa) VUM 20C/452R (B.1.526.1)
VUM 20C/452R (B.1.427 / B.1.429) VUM 19B/501Y (A.27)

Substantial in vitro data:
- Reduced efficacy of the neutralizing humoral response
(post-infection, post-vaccination, and monoclonal antibodies)
- Increased affinity of the virus for its cellular receptor

Epidemiological data:
- Increase in the number of variants carrying this mutation
- Increase in the detection of this mutation internationally (7.5% of total sequences deposited in GISAID and collected between April 1, 2021, and June 1, 2020)

A necessary transition period to ensure data quality

This development enables more responsive monitoring of the spread of variants carrying these variants of interest at the national level and in the most affected regions. To account for this change, information will be published on the Santé publique France website during a transitional period, prior to the upcoming release of consolidated data as open data on the Géodes website.

As with any change to information systems and the data reporting chain, a period is indeed needed to assess the actual ramp-up, the quality of the data received, and its consistency with available data.

The surveillance system established by Santé publique France will continue to rely on periodic surveys based on the sequencing of a random sample of SARS-CoV-2-positive specimens (Flash surveys) conducted by the EMERGEN consortium, as well as on enhanced epidemiological monitoring across the entire country

In addition, starting Thursday, June 17, 2021, the following will be available on our website:

  • The number of screening results recorded under the new classification system and their proportion among positive tests (TAG and PCR) at the national level for the rolling 7-day period from day 3 to day 9. PCR screenings performed following a positive antigen test are not yet included in this indicator. Consequently, the percentage of screened PCRs is underestimated.

  • The proportion of results indicating the presence of each of the E484K, E484Q, and L452R mutations among screened tests where the mutation is being tested for, regardless of the result for other mutations, at the national level, for the rolling 7-day period J-3 to J-9

  • The table derived from the risk analysis: available knowledge on the E484K, E484Q, and L452R mutations or the variants carrying them

  • And additionally in the weekly epidemiological updates and on the page dedicated to variants on our website: information regarding the circulation of variants (Flash Surveys) and risk analyses produced every two weeks.

The open-data publication of mutation screening data is expected to take place by the end of June 2021. Details will be provided at a later date.

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