A recent study by researchers in France has compared the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. The team found a significant transmission advantage of V2 (from lineage B.1.351) over V1 (from lineage B.1.1.7). A pre-print version of the research paper is available on the medRxiv* server.

The B.1.1.7/V1 is currently causing the majority of infections in Europe and North America, whereas the B.1.351/V2 is dominant in South Africa. The variant V3 from lineage P.1 has become dominant in Brazil and South America. These variants are classified as Variants of Concern (VOC).

According to the Centers for Disease Control and Prevention (CDC), a variant of concern is a variant for which there is evidence of an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), a significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.’

Since January 2021, the national guideline is to test all positive samples in France with an additional real-time polymerase chain reaction reverse transcription (RT-PCR), for an early assessment of diffusion and possible expansion of the SARS-CoV-2 lineage. This will help detect the rapid SARS-CoV-2 variant spread. More specifically, since April 2021, laboratories are advised to test for variant-specific RT-PCRs targeting the N501Y and E484K mutations.

In this study, the researchers analyzed 36,590 variant-specific RT-PCR tests performed on samples collected between April 12 and May 7, 2021, in 13 French regions. The data included individuals aging from 5 years to 80 years.

“17.3% of the tests could not be interpreted, because of Ct value too high to keep an equal sensitivity for the N501Y and E484K targets, and were removed from the analysis,” the researchers added. Therefore, to avoid biasing the variant screening, they ignored all the tests with cycle thresholds (Ct) values above 30.

They found that contrary to January to March 2021, the V2 variant had a significant transmission advantage over V1 in some regions (15.1 to 16.1% in Îlede-France and 16.1 to 18.8% in Hauts-de-France).

Because the specificity of the variant-specific RT-PCR used in this study targeted only 2 mutations and thus was limited, the researchers probed sequencing profiles to gain further insights. They sequenced all the samples collected on March 30, and found 79.1% of the viruses from the B.1.1.7 / V1 lineage, in the 478 samples. They found that the other prevalent lineages were B.1.351 / V2 (7.9%), B.1.525 (4.4%), and B.1.214 (2.3%), and the rest represented less than 2% of the samples (lineage P.1 / V3 being below 1%).

In this study, the researchers noted that the samples with only the N501Y mutation are treated as V1, samples with both mutations as V2, samples with only the E484K mutation as B.1.525, and samples with no mutation as wild types (B.1.214 being rare).

While the researchers found that the older patients were more infected by V1 than by V2 or B.1.525, in hospital settings, V2 was overrepresented compared to V1.

In the region-specific trends, they analyzed that infection by a wild type or a B.1.525 / V2 the virus was less probable than by V1. Conversely, in Îlede-France, and to a lesser extent in Hauts-de-France and Nouvelle-Aquitaine, the researchers found that the risk of being infected by V2 instead of V1 significantly increases with time. The V2 variant is reported to have immune evasion properties.

Therefore, Île-de-France being one of the French regions the most impacted to date by the epidemic, it is sensible that we detect the shift in transmission advantage there because the proportion of individuals with natural immunity is high.”

As vaccination adds to the favorable selection of immune escape mutants, the researchers call for a more detailed analysis to understand the link between the transmission advantage of the V2 variant and the proportion of the population immunized in different French regions.

Notably, most of the tests analyzed in this study are performed in a declining epidemic (during the third national lockdown). However, the researchers believe, “it is unlikely that the lock-down per se would affect the transmission of the variants any differently.”

Given the high COVID-19 incidence in France and the uncertainties regarding the lock-down lifting, these results call for particular care to avoid another epidemic wave in the country, the researchers write.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Ramya Dwivedi

Ramya has a Ph.D. in Biotechnology from the National Chemical Laboratories (CSIR-NCL), in Pune. Her work consisted of functionalizing nanoparticles with different molecules of biological interest, studying the reaction system and establishing useful applications.