Variants of immune evasion of SARS-CoV-2 B.1.1.420 and B.1.617.1 reported in France – fr

Variants of immune evasion of SARS-CoV-2 B.1.1.420 and B.1.617.1 reported in France – fr

Since its emergence in Wuhan, China in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 (coronavirus disease 2019), has spread rapidly, many variants being observed around the world. A high transmission rate would indicate an ongoing process of positive selection of variants, which could allow the virus to acquire advantageous genetic traits. Emerging variants are likely to be more transmissible, more pathogenic, and more likely to evade natural or vaccine immunity.

Therefore, genomic surveillance of SARS-CoV-2 and its variants is essential. It provides an overview of the mechanisms of viral spread around the world. Variants include N501Y, E484K, or L452R mutations on the gene encoding the viral spike protein. The two new Indian variants recently identified are the N440K and E484Q and L452R mutations associated with an immune response and altered immune reactions.

Researchers discovered the first N440K variant and the new Indian variants E484Q and L452R isolated in France in a recent study. They presented the genetic mutations in the isolated genomes and the phylogenetic tree, including these strains among the different clades of SARS-CoV-2. This work is posted on the bioRxiv * pre-print server.

“Real-time close-range surveillance variants could help the scientific community prevent rapid spread and raise alarms on potentially dangerous variants. “

The two new variants with mutations N440K and E484Q and L452R are associated with an alteration of the antibody response and immune reactions. These were first identified in India. Alphabio’s medical laboratory in Marseille (France), in collaboration with the PACA Regional Health Agency, Marseille, has started a real-time genomic investigation of circulating variants of SARS-CoV-2 based on whole genome sequencing at broadband March 2021.

The project aims to characterize specific clusters and identify new emerging variants responsible for increased infectivity and / or immune leakage. In this study, the researchers described for the first time the characterization of the two variants of immune leakage.

They isolated the first N440K escape variant from a 36-year-old French woman and her 37-year-old husband on March 16, 2021. Both had mild symptoms, including asthenia and cough, with no comorbid or severity factors and were recovering. . They were not vaccinated against the COVID-19 virus and had no history of travel abroad.

The researchers isolated the second E484Q – L452R variant of a 37-year-old Indian from Mumbai, who arrived in Marseille to board a ship as a crew member. On March 19, 2021, after developing mild symptoms including asthenia (physical weakness and lack of energy) and cough without comorbidity or severity factors, he tested positive for the first time for SARS-CoV-2. He was immediately isolated in quarantine in a hotel in the city.

Analysis of the entire genome sequencing revealed that these belonged to lines B.1.1.420 and B.1.617.1 – these strains belong to Clade 20B and 20A respectively and are distant from other variants of concern.

The researchers stress that the accurate and timely detection of new variants that may exhibit greater infectivity or worse clinical symptoms, including immune leakage, will be extremely important in preventing a worsening of the pandemic.

“In this study, the discovery of the first N440K variation isolated in France from infected subjects with no recent travel history highlights the importance of monitoring the impact of new viral variants,” the researchers stressed.

It is well known that the N440K mutation has been reported in India to be resistant to class 3 monoclonal antibodies (mAbs) C135 and REGN10987, in addition to having improved binding affinity with the ACE2 receptor (angiotensin converting enzyme). in humans. It may also have the potential for a higher transmission rate.

Although it is not yet known whether the mutation affects the replicative capacity of the virus, the researchers warn that as a new emerging variant, its low prevalence could also be explained by the lack of sequencing in the infected population carrying the virus. this mutation. Thus leading to an underestimation of the diffusion of this variant, they hypothesized that the emergence of the N440K variant is the result of intrahost evolution.

This last case of the identification of the B.1.617.1 genome with the combination of the two RBD 135 E484Q or L452R mutations noted in this study raises the question of the lack of real control over the mobility of people from areas where worrying variants are circulating. .

“In view of the immune leakage conferred by the N440K, E484Q and L452R mutations, these new variants require further study. “

Despite vaccines and mitigation measures, the COVID-19 pandemic continues, with more variants and more infections every day. If it is a variant that accelerates the spread of the virus in human populations, the necessary measures must be taken quickly to mitigate the epidemic. More coronavirus genomes need to be sequenced around the world to accurately identify the emergence of these mutations and other variants.

*Important Notice

bioRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behaviors, or treated as established information.


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